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Biomedical subjects

R Dahl

Publications and source records attributed to R Dahl.

At least 19 recordsLinked to original sources

Serum IgE in nonatopic smokers, nonsmokers, and recent exsmokers: relation to lung function, airway symptoms, and atopic predisposition.

The influence of smoking on serum IgE (s-IgE) was studied in a selected nonatopic population. The variation in s-IgE was followed during 1 year of smoking abstinence. The study included 287 smokers and 137 never smokers. IgE was higher in smokers compared with IgE in never smokers (p less than 0.005). Male smokers had higher s-IgE than female smokers (p less than 0.01). S-IgE was independent of age and claims of atopy among first-degree relatives. Weighted pack-years consumption was defined for cigarette smokers by modifying pack-years consumption by nicotine content of the brand smoked. Weighted pack-years consumption was associated with level of s-IgE (p less than 0.05). S-IgE was higher in smokers with airway symptoms compared with that in smokers without symptoms (p less than 0.01). In smokers older than 50 years of age, there tended to be decreased FEV1 residuals (0.05 less than p less than 0.06), and presence of airway symptoms was (p less than 0.03) associated with high levels of s-IgE independent of each other. In 92 quitters, s-IgE increased during the first 26 weeks of abstinence (p less than 0.05), and after 1 year, s-IgE had returned to baseline. The increase was only observed in smokers younger than 40 years and had no relation to variations in FEV1 during the 1-year follow-up. The increase in s-IgE after smoking cessation was transient, of minor clinical importance, and probably caused by a relief from an immunosuppressive influence.

Adult

Synthesis of 18F-labeled fluconazole and positron emission tomography studies in rabbits.

[4-18F] 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-l-yl)-2-propanol [( 4-18F] fluconazole) was synthesized from its amino precursor. Fieldel-Crafts acylation of 3-fluoroacetanilide with chloroacetyl chloride produced 2'-fluoro-4'-acteamido-2-(1H-1,2,4-triazole-1-yl) acetophenone in 12% yield. Sequential reaction with (1) dimethylsulphoxonium methylide and (2) 1,2,4-triazole followed by in situ hydrolysis resulted in 2-(2-fluoro-4-aminophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-2-propan ol in 19% yield. A modified Schiemann reaction on this product resulted in [4-18F]fluconazole with a radiochemical yield of 1.0-2.0% (EOS) within 2 h. [4-18F]Fluconazole was used to measure the pharmacokinetics of fluconazole in rats by measurement of radioactivity in excised tissues and in rabbits by PET. In both species, there was rapid equilibration of [4-18F]fluconazole to a relatively uniform distribution of radioactivity in most organs.

Animals

Dexamethasone suppression test in children with major depressive disorder.

The authors report a study of 24-hour serial cortisol determinations, measured during baseline and after the administration of 0.25 and 0.5 mg of dexamethasone in a sample of predominantly outpatient children with major depressive disorder, nonaffective psychiatric controls, and normal controls. In this sample, 24-hour baseline cortisol and the dexamethasone suppression test (DST) do not discriminate between the three groups. In addition, the authors measured 24-hour serum dexamethasone levels. There were no significant between group differences in serum dexamethasone. These results raise questions as to the utility of this test in the diagnosis of affective disorders in children. Possible reasons for the discrepancies in the dexamethasone suppression test results between in- and outpatient studies are discussed.

Administration, Oral

Immunotherapy in patients allergic to cat and dog dander. I. Clinical results.

Twenty-four asthmatics allergic to cat and/or dog dander were included in a study to examine the efficacy and safety of immunotherapy (IT) with partially purified, standardized extracts of cat or dog dander. In the first placebo controlled, double-blind part of the study, 10 patients were treated with extracts of both cat and dog, 12 with cat extracts and 2 with dog extracts. Fifteen patients received active IT and 9 placebo injections. Patients treated with both extracts received active extracts only, or placebo only. Bronchial allergen challenge after 5 months demonstrated a significant fall in sensitivity to cat (P = 0.04) in patients treated with cat extracts. No significant changes were found in sensitivity to dog after treatment with dog dander extract or in the placebo groups. During this period, bronchial sensitivity to histamine did not change significantly in any of the groups. To examine the effect of more prolonged IT, 19 patients allergic to cat (17) and/or dog (9) were treated for 12 months. Bronchial sensitivity to cat decreased further (P = 0.003), while no significant change was found in dog extract-treated patients. In cat extract-treated patients a significant decrease in bronchial histamine sensitivity developed (P = 0.02). Systemic side effects were few, but in some cases, local side effects were a dose-limiting factor. This study demonstrated that IT with cat extract may benefit cat-allergic asthmatics, whereas no influence of IT with dog extract was detected in dog-sensitive asthmatics.

Adolescent

A comparative study of four different bronchial challenge tests.

The correlation between 4 commonly used tests for assessment of airway hyperresponsiveness was studied in 10 asthmatics by performing bronchial challenges with histamine, ultrasonically nebulised distilled water (UNDW), exercise, and a relevant allergen. All tests were performed within 4 weeks for each individual and at least 48 h apart. A significant correlation was found between histamine challenge and exercise challenge (r = -0.74). Other correlations were substantial (0.4-0.5) but did not reach statistical significance. This suggests that the challenges have different mechanisms or pathways leading to bronchoconstriction, and assessment of the pattern of individual patients' bronchial hyperresponsiveness may require application of a number of different bronchial challenge tests. For routine use histamine challenge seems the most appropriate.

Administration, Inhalation

Cytoskeleton disruption and apical redistribution of proximal tubule Na(+)-K(+)-ATPase during ischemia.

The polar distribution of Na(+)-K(+)-ATPase to the basolateral membrane of proximal tubule cells is essential for the efficient and vectorial reabsorption of Na+ and may be dependent on the formation of a metabolically stable, detergent-insoluble complex of Na(+)-K(+)-ATPase with the actin membrane cytoskeleton. The present studies utilized immunocytochemical techniques to demonstrate and quantify the apical redistribution of Na(+)-K(+)-ATPase during mild ischemia (15 min) that occurred in proximal (1.3 +/- 0.9 vs. 4.5 +/- 1.1 particles/100 microns surface membrane, P less than 0.01) but not distal tubule cells. Treatment of control apical membranes with 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanoate (A2C), a fluidizing agent, markedly increased membrane fluidity without any effect on Na(+)-K(+)-ATPase activity. In brush-border membrane vesicles isolated after ischemia, however, A2C further increased an already elevated Na(+)-K(+)-ATPase activity. During ischemia, total cellular Na(+)-K(+)-ATPase activity remained unaltered, but the Triton X-100-soluble (noncytoskeleton associated) fraction of Na(+)-K(+)-ATPase increased significantly following 15 and 30 min. There was a corresponding decrease in the Triton X-100-insoluble fraction of Na(+)-K(+)-ATPase, with the ratio of detergent-soluble to -insoluble Na(+)-K(+)-ATPase increasing from 13 +/- 2 to 32 +/- 5% (P less than 0.01) during 30 min of ischemia. Western blot analysis of the Triton X-100-soluble fraction, following 30 min of ischemic injury, revealed the presence of Na(+)-K(+)-ATPase, actin, fodrin, and uvomorulin. However, in a fraction highly enriched for Na(+)-K(+)-ATPase, neither actin, fodrin, nor uvomorulin was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Alpha 1-antitrypsin alleles in patients with pulmonary emphysema, detected by DNA amplification (PCR) and oligonucleotide probes.

Alpha 1-antitrypsin (AAT) deficiency is a serious predisposing factor for the development of pulmonary emphysema. Twelve representative Danish families were studied. AAT typing was performed as a comparative study between the traditional protein typing by isoelectrical focusing and the deoxyribonucleic acid (DNA) technique of enzymatic amplification and subsequent typing with radioactively labelled oligonucleotide probes. On the basis of clinical and radiological signs of pulmonary emphysema, 25 patients were selected. AAT typing was performed by use of the two techniques in combination, in search for new point-mutations among the patients. Results obtained with the two techniques were discordant in one patient, suggesting an unknown variant. The unexpectedly high PiZ frequency of 0.22 found in the study group is discussed.

Adult

[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

[Allergy to insect stings].

Components in the insect venom and probably also in their saliva may have direct toxic effects or may cause sensitization and may result in allergic reactions to subsequent stings. In Denmark, only the stings of honey bees and wasps (yellow jackets) are of clinical significance and it is important to be aware that these insects contain separate allergenic components. Clinical manifestations following stings are observed from all of the organ systems on the whole. The commonest are itching of the skin, urticaria, possibly angioedema and slight generalized symptoms with vertigo, headache and fatigue. Life-threatening reactions may also occur and one or two fatal cases are registered annually in Denmark. It may be difficult to decide whether an allergic or a toxic reaction is involved on the basis of the symptoms. Possible IgE-sensitization must therefore be assessed by means of a prick test and measurement of specific IgE. The main treatment in cases of acute systemic reactions is adrenaline which may possibly be supplemented with antihistamine and corticosteroid. In cases of massive local reactions and urticaria, antihistamines will, as a rule, prove sufficient. Hyposensitization with insect venom preparations eliminates the future risk for systemic insect sting reactions practically entirely and this must be recommended for patients with demonstrated IgE-sensitizing and generalized reactions. At present, treatment should be continued for three to five years and protection lasts for a series of years after cessation of treatment.

Humans

[Long-term treatment of chronic bronchitis with pulmonary physiotherapy with and without positive expiratory pressure].

In a prospective, randomized, controlled study, treatment of chronic bronchitis with self-administered chest physiotherapy alone (control) or with positive expiratory pressure (PEP) by mask was studied. Forty-three patients completed the study (n = 20 PEP, and n = 23 control). After instruction, the treatments were self-administered twice daily for 12 months (34 patients) and five months (9 patients). The patients completed a diary concerning symptoms twice weekly. An acute exacerbation (AE) was defined as the appearance of mucopurulent or purulent sputum and increasing cough and one or more of the following symptoms: temperature greater than or equal to 38 degrees C, general malaise, increased dyspnea, increased mucus production, increased thickness of mucus or increased difficulty in expectoration. The number of AE were calculated from the diaries. The incidence of AE was significantly lower in the PEP group (p less than 0.0005). In the PEP group, three patients had a total of six AE, compared to 12 patients with 28 AE in the control group. The PEP group also used less antibiotics (p less than 0.005). Treatment with a simple PEP device can reduce morbidity in patients with chronic bronchitis.

Adult

Effect on smoking cessation of silver acetate, nicotine and ordinary chewing gum. Influence of smoking history.

In a randomized smoking cessation study 211, 203 and 82 persons were supported with nicotine, silver acetate and ordinary chewing gum, respectively. After 26 weeks there was no overall difference in number of abstainers between treatments. Participants were divided into subsets with low and high weighted packyears consumption (WPY) which modifies tobacco consumption by nicotine content. Abstainer rates in the total population controlled for treatment decreased with increasing WPY (P less than 0.005). In participants with low WPY abstainer rate was higher in the silver acetate group compared to the nicotine (P less than 0.0005) and ordinary (P less than 0.05) chewing gum groups. Nicotine chewing gum was more effective than silver acetate (P less than 0.05) and ordinary (P less than 0.05) chewing gum in smokers with high WPY. Ratings on some inconveniences experienced during earlier attempts to quit smoking influenced the ability to break the habit but had no influence on chewing gum effects. This study indicated that through consideration of smoking history it should be possible to individualize pharmacological support to smokers wanting to quit, with silver acetate chewing gum most effective for smokers with a low WPY and nicotine chewing gum most effective for smokers with a high WPY.

Acetates

Treatment of chronic bronchitis with terbutaline inhaled from a cone spacer with and without positive expiratory pressure.

Patients with chronic bronchitis were randomly allocated to 4 weeks treatment with terbutaline 0.5 mg inhaled through a cone spacer with an expiratory resistance creating a positive expiratory pressure (+PEP group) or without (-PEP group). The patients recorded their symptoms in a diary and peak expiratory flow (PEFR) was measured before and after each inhalation. PEFR increased significantly after inhaled terbutaline both with and without PEP. The mean increase in PEFR after terbutaline inhalations was significantly greater (p less than 0.0001) in the +PEP group (24 L/min) compared to the -PEP group (17 L/min). The +PEP group had less sputum and less difficulty with coughing up sputum compared to the -PEP group. This study showed a small but significant enhancement of the bronchodilation and a beneficial effect on symptoms when inhalation of beta-2-agonist was combined with PEP in patients with chronic bronchitis.

Bronchitis

Eosinophils in exercise-induced asthma.

The variations in serum levels of eosinophil cationic protein (ECP) have been measured after exercise challenge of 13 patients with asthma with exercise-induced asthma (EIA) and nine patients with asthma without EIA. The patients were treated before exercise in a randomized and blinded fashion with inhalation of one dose of either disodium chromoglycate, terbutaline, or budesonide and in an open study with 4 weeks of inhaled budesonide. In the group with EIA, there was, in some patients, an initial increase in serum levels of ECP after exercise, but 60 minutes after exercise, the levels were significantly reduced (p less than 0.001). Disodium chromoglycate and 4 weeks of budesonide treatment inhibited this reduction. Histamine challenge of the group with EIA produced a similar fall in serum ECP levels (p less than 0.001). The group without EIA had initially lower levels of ECP than the group with EIA (p less than 0.05 to p less than 0.01), and ECP stayed unaltered after exercise. The preexercise serum ECP levels correlated significantly to the maximal fall in peak expiratory flow in the untreated group (r = 0.91; p less than 0.001) and in the group receiving one dose of budesonide (r = 0.62; p less than 0.05). The blood eosinophil counts were unchanged after challenge and not related to lung function. The results suggest that the ECP content in serum reflects the degree of allergic inflammation in the lungs and thereby the degree of bronchial hyperreactivity.

Adolescent

In-hospital sting challenge in insect venom-allergic patients after stopping venom immunotherapy.

Immunotherapy (IT) in venom-allergic patients has been demonstrated to provide a highly efficient protection from severe reactions to a re-sting. It is not known whether this protection will persist after IT is stopped in patients with remaining venom sensitivity. In 25 adult patients with a previous severe systemic reaction to a Hymenoptera insect sting, 28 in-hospital sting challenges after stopping IT resulted in no systemic reactions. The mean duration of venom IT was 42.8 months (range, 36 to 83 months), and the mean time interval from the time IT was stopped until sting challenge was, in mean, 25.2 months (range, 12 to 36 months). The mean venom-specific IgE after stopping IT was 2.4 PRU/ml (range, 0 to 16.9 PRU/ml), at the day of sting challenge, 2.7 PRU/ml (range, 0 to 22 PRU/ml), and 2 weeks later, 2.4 PRU/ml (range, 0.02 to 27.8 PRU/ml). These changes in IgE were not significant. Venom-specific IgG concentration when IT was stopped was 64 PU/ml (range, 20 to 144 PU/ml), decreasing significantly to the day of sting challenge to 41.1 PU/ml (range, 13 to 84 PU/ml), and 2 weeks later, a significant increase to a mean of 53.5 PU/ml (range, 12 to 117 PU/ml) was found. Our results suggest that venom IT may be stopped after 3 years, regardless of the level of specific antibodies. To confirm this finding, a larger number of patients should be studied.

Adult