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Biomedical subjects

R Dahl

Publications and source records attributed to R Dahl.

At least 145 records · Page 8Linked to original sources
PubMed1993

Mechanism of ischemia-enhanced aminoglycoside binding and uptake by proximal tubule cells.

Preceding ischemia or concurrent hypotension is known to enhance aminoglycoside nephrotoxicity; however, the underlying mechanisms responsible have not been determined. To investigate the effect of preceding mild ischemia on cellular gentamicin handling, brush-border membrane vesicle binding and in vivo cellular gentamicin uptake were quantified using [3H]gentamicin as a tracer. Fifteen minutes of ischemia resulted in a marked increase in apical membrane gentamicin binding (2.8 +/- 0.4 vs. 4.9 +/- 0.8 nmol/mg protein, P < 0.01). This increase was associated with an increased number of binding sites (3.7 +/- 0.3 vs. 9.1 +/- 2.3 nmol/mg protein, P < 0.01) and a reduced binding affinity (11.8 +/- 2.2 vs. 27.7 +/- 10.4 microM, P < 0.01). This increase in gentamicin binding was accompanied by alterations in apical membrane phospholipids including a doubling of phosphatidylinositol (PI) levels (13.8 +/- 0.4 vs. 27.5 +/- 3.1 nmol/mg protein, P < 0.01). Furthermore, treatment of apical membrane vesicles with PI-specific phospholipase C markedly reduced the difference in gentamicin binding between paired control and ischemic membrane fractions. Increased gentamicin binding was associated with increased in vivo uptake of gentamicin by S1/S2 and S3 cells. Outer cortical uptake of gentamicin increased from 2.18 +/- 0.39 to 2.68 +/- 0.27 nmol/mg protein (P < 0.01) after 15 min of ischemia and 4 h of reperfusion. Juxtamedullary uptake also increased from 1.39 +/- 0.31 to 1.75 +/- 0.12 nmol/mg protein (P < 0.01). Immunocytochemical techniques, utilizing immunogold labeling, showed gentamicin was taken up via the receptor-mediated endocytic pathway by S1/S2 and S3 cells. After ischemic injury gentamicin was localized in abnormal intracellular accumulations in S3 but not S1 or S2 cells. Taken together, these data indicate ischemia results in a marked increase in apical gentamicin binding due to increases in apical PI content. This is associated with increased internalization by S1/S2 and S3 cells and abnormal intracellular compartmentalization of gentamicin within S3 cells.

Aminoglycosides↗
PubMed1993

Inhaled beta 2-agonist and positive expiratory pressure in bronchial asthma. Influence on airway resistance and functional residual capacity.

INTRODUCTION: Positive expiratory airway pressure seems to dilate narrowed or collapsed airways, but this may be accompanied by a maintained and harmful increase in resting lung volume in obstructive pulmonary disease. PURPOSE: To evaluate the influence of inhaled terbutaline and positive expiratory pressure (PEP) on airway resistance (Raw) and functional residual capacity (FRC) in bronchial asthma. DESIGN: Randomized crossover design, single blind with regard to inhaled medication, open with regard to PEP (PEP can be felt). MATERIAL AND METHODS: Ten patients with bronchial asthma inhaled placebo and terbutaline in doses of 0.125 mg, 0.5 mg, and 1.5 mg by cone spacer combined with a facemask giving 0, 10, or 15 cm H2O PEP on separate days. FRC and Raw were measured by body plethysmography before and after inhalations. Data were analyzed by analysis of variance with terbutaline dose and PEP as factor levels. RESULTS: The effect of terbutaline: Raw decreased significantly (p < 0.0001) after 0.125 mg and 1.5 mg. The FRC did not change significantly. The effect of PEP: Raw decreased, but significantly only when the dose of 1.5 mg terbutaline was excluded from the analysis. Raw decreased with PEP 10 and 15 cm H2O, mean 0.6 (95 percent CI: -1.1, -0.2) and 0.9 (95 percent CI: -1.3, -0.4) cm H2O/L/s. The FRC did not change significantly with the PEP level. CONCLUSION: PEP only had influence on Raw when insufficient doses of terbutaline were inhaled, whereas once an efficient dose of terbutaline was administered, significant bronchodilation was achieved with or without PEP. Positive expiratory pressure did not increase FRC.

Administration, Inhalation↗
PubMed1993

A dose-ranging study of fluticasone propionate in adult patients with moderate asthma. International Study Group.

In this 4-week, multicenter, double-blind, randomized, parallel group study, the dose-effect relationship of four doses of inhaled fluticasone propionate (50, 100, 200, and 400 micrograms twice daily) was investigated and compared with beclomethasone dipropionate, 200 micrograms twice daily. A total of 672 patients with moderate asthma currently receiving 1,000 micrograms/d or less of an inhaled steroid were recruited. The study demonstrated a significant dose-related improvement in lung function with fluticasone propionate. Linear dose-related increases were observed in morning (increase per doubling dose was 4.3 L/min; 95 percent confidence interval [CI], 1.8, 6.8 L/min; p = 0.001) and evening peak expiratory flow rate (PEFR) (increase per doubling dose was 3.0 L/min; 95 percent CI, 0.5, 5.5 L/min; p = 0.017), clinic lung function (at 4 weeks, increase in percent predicted PEFR per doubling dose = 1.1 percent; 95 percent CI, 0.2, 2.1 percent; p = 0.022; increase in percent predicted FEV1 per doubling dose = 1.1 percent; 95 percent CI, 0.3, 1.9 percent; p = 0.10:increase in percent predicted FVC per doubling dose = 1.3 percent, 95 percent CI, 0.5, 2.1 percent; p = 0.001), and the percentage of symptom-free days over days 1 to 14 of treatment (increase per doubling dose = 1.9, 95 percent CI, 0.0, 3.9; p = 0.048). There was also a dose-related reduction in extra bronchodilator usage (days 1 to 14 p = 0.002; days 15 to 28 p = 0.01). In addition, there was a significant decrease in diurnal variation with increasing doses of fluticasone propionate (decrease per doubling dose = 2.0 L/min, 95 percent CI, 0.4; p = 0.024). The number of asthma exacerbations was also reduced as the dose of fluticasone propionate increased. Fluticasone propionate was well tolerated, adverse events were few, and there was a similar incidence in all groups. Furthermore, there was no evidence of any hypothalamic pituitary adrenal axis suppression. The data from the study were consistent with other clinical studies that have shown fluticasone propionate to be more potent than beclomethasone dipropionate in terms of improvement in lung function. In conclusion, this study provided evidence of a dose-related improvement in asthma control for fluticasone propionate in the dose range 100 to 800 micrograms daily, in patients with moderate asthma.

Administration, Topical↗
PubMed1993

The effect of single doses of inhaled beclomethasone dipropionate on the circadian rhythm in serum osteocalcin in normals.

A single dose of 2.5 mg prednisone leads to a significant transient decrease in serum osteocalcin, which is only demonstrated by frequent serum sampling. The aim of the present study was to evaluate whether a single dose of inhaled beclomethasone dipropionate causes transient changes in serum osteocalcin, indicating a systemic effect on bone cells. In a double-blind, placebo controlled, cross-over design we evaluated the effects of single doses of 250 micrograms and 1000 micrograms beclomethasone on the circadian rhythm in serum osteocalcin. Fifteen normal subjects aged 23-38 years were studied twice with an interval of one week with hourly blood sampling from 16.30 until 17.00 the following day; 1000 micrograms beclomethasone, but not 250 micrograms, suppressed serum cortisol by 14.4 +/- 6.7% (p = 0.03). Neither of the beclomethasone doses significantly altered the time pattern of serum osteocalcin. We conclude that a single inhaled dose of beclomethasone in the therapeutical range does not acutely influence osteoblastic activity as judged from serial measurements of serum osteocalcin.

Administration, Inhalation↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
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↗
PubMed1991

[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↗
PubMed1991

[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↗