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Biomedical subjects

R Dahl

Publications and source records attributed to R Dahl.

At least 127 records · Page 7Linked to original sources

Intranasal levocabastine for the treatment of seasonal allergic rhinitis: a multicentre, double-blind, placebo-controlled trial.

In this international, multicentre, randomized, double-blind, parallel-group, placebo-controlled trial 262 patients participated to assess the efficacy and tolerability of levocabastine nasal spray in the treatment of seasonal allergic rhinitis. Patients were randomized to receive either twice daily 0.05% levocabastine or matching placebo nasal spray with a treatment duration of four weeks. Assessments of global therapeutic efficacy favoured levocabastine. At the end of the trial, 55% of levocabastine-treated patients considered therapeutic efficacy to be excellent or good compared to 36% of those who received placebo (p < 0.001). The corresponding values for the investigator assessments were 54% and 37% (p < 0.001), respectively. Analysis of patients' diary data showed significantly lower AUCs for all parameters in the levocabastine group (p < 0.05). Investigator assessments revealed a trend towards a greater reduction in individual symptom severity from baseline in levocabastine-treated patients compared to placebo-treated controls. Adverse experiences were reported by 21% of levocabastine-treated patients and by 19% of those who received placebo, with no statistically significant differences in incidence or type. Headache and local reactions following application were the most frequently reported adverse events. Levocabastine nasal spray appears to be effective and well-tolerated for the treatment of seasonal allergic rhinitis and is an alternative to oral antihistamines.

Administration, Intranasal↗

[Occurrence of housedust mites in dwellings. Relation to ventilation and humidity].

The concentration of house-dust mites (Der. spp.) was investigated in 96 Danish dwellings and bedroom air-exchange rates, humidity and temperature was measured contemporaneously in all the dwellings. A positive correlation was found between indoor air humidity and mite concentration, and an inverse correlation was found between house-dust mite concentration and indoor air-exchange. Dwellings of mite-allergic persons had a higher concentration of house-dust mites compared with those of the non-mite-allergic group. House-dust mite concentration was above the proposed limit in 76% of the homes of mite allergic persons and in 48% of the homes of non-sensitive persons. The high proportion of dwellings infested with house-dust mites, when compared with previous measurements, suggests an increased prevalence of house-dust mites in Danish dwellings. The results support the concept that reduced ventilation in dwellings involves a risk of increased house-dust mite exposure.

Air Pollution, Indoor↗

Quantitative brain FDG/PET studies using dynamic aortic imaging.

Positron emission tomography (PET) measurements of cerebral glucose utilization using 18F-fluorodeoxyglucose (FDG) are a useful tool in the investigation of localized brain function in normal and disease states. A major impediment to the application of FDG/PET in clinical investigation has been the need for arterial blood sampling to quantify cerebral glucose metabolism (CMRGlc). Qualitative studies, though informative in a variety of clinical settings, are of limited value for research applications and do not utilize the inherent quantitative nature of PET. We present a novel PET technique employing a whole-body PET tomograph with abdominal aortic imaging from 0 to 30 min as an alternative to arterial blood sampling to obtain the input function for cerebral metabolic rate calculations. Two or three arterial samples taken during the 10-45 min period were used to scale and extend the blood curve and the brain was imaged from 35-55 min post-injection. We performed 12 studies in which both arterial blood sampling and aortic scans were obtained. We found the correlation of global metabolic rates (GMR) when comparing the two techniques to be extremely high (R2 = 0.99). This suggests that the use of dynamic aortic imaging is less invasive and a viable alternative to arterial blood sampling in quantitative FDG/PET imaging.

Algorithms↗

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↗

Clinical efficacy of reduction in house-dust mite exposure in specially designed, mechanically ventilated "healthy" homes.

In temperate climates, energy-conserving measures may increase indoor humidity, enhancing house-dust mite (HDM) growth. Movement of families to "healthy" homes with mechanical ventilation systems reduced HDM exposure. The effect on asthma control of moving to the "healthy" homes was studied in 14 asthmatic patients allergic to HDM. Base-line evaluations of lung function, asthma symptoms, and medication requirements were made before moving and again after 5 and 15 months' residence. A control group of 11 mite-sensitive asthmatic patients who did not move were examined contemporaneously with the study group at base line and at the first follow-up investigation. After 5 months, the residents of the "healthy" homes improved in forced expiratory volume in 1 s (FEV1), medicine score, and serum IgE. These changes were significantly different from control group measurements. After 15 months, statistically significant improvements from base line were found in FEV1, average daily peak expiratory flow values, medicine score, symptom score, and serum IgE. Insignificant trends toward improvement were seen in provocation concentration of histamine and blood eosinophils. A significant relation was found between reduction in medicine score and fall in HDM exposure. The present study shows that a specific HDM-avoidance procedure can result in an overall, clinical improvement in HDM-sensitive asthmatic patients.

Adolescent↗

House-dust mite exposure reduction in specially designed, mechanically ventilated "healthy" homes.

Exposure to house-dust mites (Dermatophagoides spp.) was investigated in 30 asthmatic patients before and after moving to homes with mechanical ventilation systems. Median house-dust mite concentration was 110 mites per gram of mattress dust at the initial investigation and 20 mites per gram at the first follow-up after a mean of 4.7 months in the new homes. This was lower (P < 0.05) than counts in a control group of 23 asthmatic patients that had unchanged counts. At a second follow-up, after 15.0 months, mite counts in the study group were further reduced (P < 0.01) from initial values. Among 16 patients, with initial mite counts above the recommended threshold limit value (TLV) of 100 mites per gram of dust, the mite counts fell, in most cases, below this TLV. Air-exchange rates increased (P < 0.001) from a median value of 0.40 air changes per hour (ach) to 1.52 ach at the second follow-up investigation. Furthermore, a reduction (P < 0.01) was found in indoor absolute air humidity, with a median value of 5.6 g of water/kg. No such changes were found in the control group. The present study indicates that reduction of air humidity through an increased supply of fresh air may significantly diminish and, in some cases, even eliminate house-dust mites in homes.

Air Conditioning↗

Characterization of the beta 2-microglobulin endocytic pathway in rat proximal tubule cells.

The uptake mechanism(s) of low-molecular-weight proteins by proximal tubule cells remains incompletely characterized. We utilized a biochemical and semiquantitative morphological approach to better characterize the endocytic pathway of an anionic protein, beta 2-microglobulin (beta 2M), in the rat proximal tubule. Indirect immunogold techniques revealed beta 2M was taken up via a classic receptor-mediated endocytic pathway. In vitro biochemical and morphological characterization of iodinated beta 2M and gold-conjugated beta 2M (gold-beta 2M) binding to isolated brush-border membrane vesicles (BBMV) documented specific and quantitatively similar binding interactions of the modified beta 2M with BBMV. Kinetic characterization of the in vivo endocytic pathway of gold-beta 2M was undertaken using microinfusion of individual tubules. beta 2M initially bound at the apical surface, was internalized into subapical coated vesicles and delivered to endosomal-like structures within 5 min, and, finally, was concentrated in lysosomal-like structures within 15 min. This uptake was inhibited by excess unconjugated beta 2M. In addition, we directly showed that uptake did not occur across the basolateral surface. Finally, by passing solubilized BBMV over beta 2M affinity columns we were able to isolate binding activity.

Animals↗

Serum eosinophilic cationic protein and lactoferrin related to smoking history and lung function.

Some smokers have an accelerated loss of lung function, possibly due to a chronic bronchial inflammation in which granulocytes are involved. Eosinophil cationic protein (ECP) and lactoferrin (LF) are granule proteins in the eosinophil and neutrophil granulocyte, respectively. We wanted to investigate the relationship of serum (s) ECP and LF concentrations to smoking history and lung function alteration. This partly cross-sectional and partly prospective study included 98 nonatopic smokers and 31 lifetime nonsmokers. As participants in a smoking cessation programme, 50 of the 98 smokers ceased smoking for > or = 1 year. Smoking history, lung function and blood samples were obtained at the start of the study, and smokers and ex-smokers also gave blood samples 3, 6 and 12 months later. s-ECP and s-LF were elevated in smokers compared to people who had never smoked. s-ECP was linearly associated with daily cigarette consumption and forced expiratory volume in one second (FEV1) residuals. In a multiple linear regression analysis, low s-ECP and high s-LF were associated with decreased FEV1 residuals. s-ECP and s-LF together accounted for 10.2% of the variation in FEV1 residuals. After smoking cessation, s-ECP and s-LF decreased within 6 months. s-ECP and s-LF are raised in smokers, and may serve as indicators of granulocyte activation. We speculate that they might contribute to prediction of accelerated lung function loss in smokers, but this question needs further investigation in a prospective study.

Blood Proteins↗

Input functions for 6-[fluorine-18]fluorodopa quantitation in parkinsonism: comparative studies and clinical correlations.

UNLABELLED: PET has been used to quantify striatal 6-[18F]fluoro-L-dopa (FDOPA) uptake as a measure of presynaptic dopaminergic function. Striatal FDOPA uptake rate constants (Ki) can be calculated using dynamic PET imaging with measurements of the plasma FDOPA input function determined either directly or by several estimation procedures. METHODS: We assessed the comparative clinical utility of these methods by calculating the striato-occipital ratio (SOR) and striatal Ki values in 12 patients with mild to moderate PD and 12 age-matched normal volunteers. The plasma FDOPA time-activity curve (KiFD); the plasma 18F time-activity curve (KiP); the occipital time-activity curve (KiOCC); and a simplified population-derived FDOPA input function (KiEFD) were used to calculate striatal Ki. RESULTS: Mean values for all striatal Ki estimates and SOR were significantly lower in the PD group. Although all measured parameters discriminated PD patients from normals, KiFD and KiEFD provided the best between-group separation. KiFD, KiEFD and KiOCC measures correlated significantly with quantitative disease severity ratings, although KiFD predicted quantitative clinical disability most accurately. CONCLUSION: These results suggest that KiFD may be an optimal marker of the parkinsonian disease process. KiEFD may be a useful alternative to KiFD for most clinical research applications.

Adult↗

Positron emission tomographic findings in Filipino X-linked dystonia-parkinsonism.

Regional and global metabolic rates for glucose (rCMRGlc and GMR) were estimated using [18F]fluorodeoxyglucose and positron emission tomography in 3 patients with Filipino X-linked dystonia-parkinsonism (lubag). In all 3 patients a selective reduction in normalized striatal glucose metabolism (rCMRGlc/GMR) was observed compared with 15 normal volunteer subjects. Presynaptic nigrostriatal function was assessed in these patients using [18F]fluorodopa and positron emission tomography. Striatal rate constants for [18F]flurodopa uptake were found to be in the normal range in all 3 patients with lubag. These findings suggest that the extrapyramidal manifestations of lubag are metabolically localized to the striatum and that clinical parkinsonism in these patients may be secondary to extranigral factors.

Adult↗

A controlled dose-response study of immunotherapy with standardized, partially purified extract of house dust mite: clinical efficacy and side effects.

BACKGROUND: Seventy-four asthmatic patients allergic to house dust mite were included in a double-blind, controlled study to establish the optimal maintenance dose of a standardized extract of Dermatophagoides pteronyssinus (Der p I) during 24 months of immunotherapy (IT). METHODS: The patients were given the following maintenance doses: 19 patients 10,000 standardized quality units (SQ-U) (group 10, 0.7 microgram Der p I), 20 patients 100,000 SQ-U (group 100, 7 micrograms Der p I), 16 patients 300,000 SQ-U (group 300, 21 micrograms Der p I), and 19 control patients (group 0) had no injections. After 24 months bronchial challenge demonstrated a dose-related increased tolerance to Der p I, group 10 (p = 0.003), group 100 (p = 0.0005), group 300 (p = 0.0007), with no change in group 0 (p = 0.6). Patients given IT had a decrease in medication and peak expiratory flow score. In total, 2104 injections were given, and 3.5% were followed by a systemic reaction, defined as a fall 15% or greater in forced expiratory volume in 1 second within 30 minutes. A dose-response relation was demonstrated, with rates of systemic reactions in percent of injections; group 10, 0.56%; group 100, 3.30%; and group 300, 7.10% (p < 0.0001). No anaphylactic reactions occurred, and no late systemic reactions were observed. This study demonstrated a dose dependence of efficacy and side effects of IT in asthmatic patients. We suggest a maintenance dose of 100,000 SQ-U (7 micrograms Der p I) as an appropriate guideline for IT with house dust mite extract.

Adolescent↗

Striatal 18F-dopa uptake: absence of an aging effect.

L-[18F]6-Fluoro-DOPA (L-[18F]6-fluoro-3,4-dihydroxyphenylalanine; FDOPA) has been used with quantitative positron emission tomography (PET) to assess presynaptic nigrostriatal dopaminergic function in life. The relationship of estimated kinetic rate constants for striatal FDOPA uptake [Ki(FDOPA)] to the normal aging process has been the subject of conflicting reports. Resolution of this issue has been hampered by methodological differences in previous FDOPA/PET investigations. We studied 19 healthy normal subjects (aged 27-77 years) and measured striatal Ki-(FDOPA) according to each of the earlier methods. While significant correlations (p < 0.005) existed between Ki(FDOPA) values estimated by the various techniques, none correlated with normal aging. We conclude that normal striatal Ki(FDOPA) values estimated using quantitative FDOPA/PET are uncorrelated with the aging process.

Adult↗

House-dust mites and associated environmental conditions in Danish homes.

The concentration of house-dust mites (Dermatophagoides pteronyssinus) was investigated in 96 Danish homes with one or more members suffering from asthma. The air-exchange rates, humidity, and temperature were measured in all the homes. A positive correlation was found between indoor air humidity and mite concentration (P < 0.01), and an inverse correlation (P = 0.027) between house-dust mite concentration and indoor air-exchange was found. Homes of mite-allergic persons had a higher concentration of house-dust mites than did those of the non-mite-allergic group. House-dust mite concentration was above the proposed limit of 10 mites/0.1 g dust in 76% of the homes of persons allergic to mites and in 48% of the homes of nonsensitive persons. The high proportion of homes infested with house-dust mites suggests an increased prevalence of house-dust mites in Danish homes. The results support the concept that reduced ventilation in homes involves a risk of increased house-dust mite exposure.

Animals↗

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↗

Noninvasive quantitative fluorodeoxyglucose PET studies with an estimated input function derived from a population-based arterial blood curve.

The authors have developed a technique to estimate input functions from a population-based arterial blood curve in positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose (FDG). A standardized pump injection was used in 34 subjects. A population-based blood curve was generated based on the first 10 subjects. In the remaining 24 subjects, an estimated input function (EIFa) was obtained by scaling the population-based curve with two arterial blood samples, one obtained at 10 minutes and the other at 45. Time integrals for EIFa and the real arterial input function (RIF) were in excellent agreement (r = .998, P < .0001). Cerebral metabolic rates for glucose calculated with EIFa and RIF and the autoradiographic method also correlated excellently (r = .992, P < .0001). Analogous correlations were achieved with arterialized venous samples as scaling factors. These results suggest that individually scaled, population-derived input functions may serve as an adequate alternative to continuous arterial blood sampling in quantitative FDG-PET imaging.

Adult↗