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Biomedical subjects

M Dahl

Publications and source records attributed to M Dahl.

At least 19 recordsLinked to original sources
PubMed2005

Well-being among children and adolescents with mobility impairment in relation to demographic data and disability characteristics.

AIM: To describe the well-being of children and adolescents with mobility impairment in relation to demographic data and disability characteristics. METHODS: The present study is based on interviews with 141 subjects aged 7 to 18?y with impaired mobility. Perceived overall well-being was measured by a nine-grade visual scale, the Snoopy scale. Independence or dependence was evaluated by the Index of Independence in Activities of Daily Living. Motor capacity was assessed with an instrument including active movements, rapidity, locomotion and balance as well as the presence and localization of pain. RESULTS: Since there were no significant differences in well-being regarding the diagnostic-related group, additional disorder/disability or the degree of disability, the impairment per se did not necessarily influence well-being negatively. Even though the majority of the children and adolescents in the study indicated a high level of well-being, several risk factors for a lower level of well-being were identified: greater age, not living with both parents, being a first-generation immigrant, having an acquired disease/injury and experience of pain. CONCLUSION: These findings increase our limited knowledge of well-being among children/adolescents with mobility impairment and provide a basis for effective care and future research.

Adolescent↗
PubMed2005

The protease inhibitor PI*S allele and COPD: a meta-analysis.

In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear. The current authors located studies that addressed the risk of COPD or measured lung function in individuals with the PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was performed. Aggregating data from six studies, the odds ratio (OR) for COPD in PI SZ compound heterozygotes compared with PI MM (normal) individuals was significantly increased at 3.26 (95% confidence intervals (CI): 1.24-8.57). In 17 cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes was 1.19 (95%CI: 1.02-1.38). However, PI MS genotype was not associated with COPD risk after correcting for smoking. Furthermore, mean forced expiratory volume in one second, a measure of airflow obstruction and a defining feature of COPD, did not differ between PI MS and PI MM individuals. There were not enough cases to summarise the risk of COPD in PI SS homozygotes. In conclusion, the results show that the PI SZ genotype is a significant risk factor for chronic obstructive pulmonary disease. The risk of chronic obstructive pulmonary disease due to the PI MS genotype is not substantially elevated.

Alleles↗
PubMed2004

Epilepsy and pregnancy: lamotrigine as main drug used.

OBJECTIVES: To study the risk of teratogenicity in infants of women with epilepsy. MATERIAL AND METHODS: Prospective data from 1996 to 2000 comprised 147 pregnancies. The most frequent antiepileptic drugs (AEDs) used were lamotrigine (LTG) 35% (n = 51), oxcarbazepine (OXC) 25% (n = 37) and valproate (VPA) 20% (n = 30). Seventy-four per cent (n = 109) received monotherapy. Folic acid supplementation was taken during first trimester by 118 patients (80%). RESULTS: The overall risk of malformations among newborns in the AED-exposed group was 3.1% (n = 4). Two children were born with multiple malformations (VPA monotherapy), two children had ventricular septal defects (one OXC monotherapy, and one OXC and LTG). The risk of malformations was 2.0% in women treated with LTG and 6.7% in women treated with VPA (NS). CONCLUSION: Despite the small number of cases in the study these data indicate that treatment with LTG during pregnancy might be relatively safe. Larger prospective studies are needed to obtain adequate power for statistical analysis.

Abnormalities, Drug-Induced↗
PubMed2004

Non-therapeutic research with minors: how do chairpersons of German research ethics committees decide?

OBJECTIVES: Clinical trials in humans in Germany-as in many other countries-must be approved by local research ethics committees (RECs). The current study has been designed to document and evaluate decisions of chairpersons of RECs in the problematic field of non-therapeutic research with minors. The authors' purpose was to examine whether non-therapeutic research was acceptable for chairpersons at all, and whether there was certainty on how to decide in research trials involving more than minimal risk. DESIGN: In a questionnaire, REC chairpersons had to evaluate five different scenarios with (in parts) non-therapeutic research. The scenarios described realistic potential research projects with minors, involving increasing levels of risk for the research participants. The chairpersons had to decide whether the respective projects should be approved. METHODS: A total of 49 German REC chairpersons were sent questionnaires; 29 questionnaires were returned. The main measurements were approval or rejection of research scenarios. RESULTS: Chairpersons of German RECs generally tend to accept non-therapeutic research with minors if the apparent risk for the participating children is low. If the risk is clearly higher than "minimal", the chairpersons' decisions differ widely. CONCLUSION: The fact that there seem to be different attitudes of chairpersons to non-therapeutic research with minors is problematic from an ethical point of view. It suggests a general uncertainty about the standards of protection for minor research participants in Germany. Therefore, further ethical and legal regulation of non-therapeutic research with minors in Germany seems necessary.

Age Factors↗
PubMed2004

Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes: a meta-analysis.

BACKGROUND: Severe alpha(1)-antitrypsin deficiency, usually related to homozygosity for the protease inhibitor (PI) Z allele, is a proven genetic risk factor for chronic obstructive pulmonary disease (COPD). The risk of COPD in PI MZ heterozygous individuals is controversial. METHODS: A search of MEDLINE from January 1966 to May 2003 identified studies that examined the risk of COPD in PI MZ individuals and studies that measured forced expiratory volume in 1 second (FEV(1)) in heterozygotes. RESULTS: In 16 studies that reported COPD as a categorical outcome, the combined odds ratio (OR) for PI MZ versus PI MM (normal genotype) was 2.31 (95% CI 1.60 to 3.35). The summary OR was higher in case-control studies (OR 2.97; 95% CI 2.08 to 4.26) than in cross sectional studies (OR 1.50; 95% CI 0.97 to 2.31) and was attenuated in studies that adjusted for cigarette smoking (OR 1.61; 95% CI 0.92 to 2.81). In seven studies that reported FEV(1) as a continuous outcome there was no difference in mean FEV(1) between PI MM and PI MZ individuals. CONCLUSIONS: Case-control studies showed increased odds of COPD in PI MZ individuals, but this finding was not confirmed in cross sectional studies. Variability in study design and quality limits the interpretation. These results are consistent with a small increase in risk of COPD in all PI MZ individuals or a larger risk in a subset. Future studies that adjust for smoking and include other COPD related phenotypes are required to conclusively determine the risk of COPD in PI MZ heterozygotes.

Forced Expiratory Volume↗
PubMed2003

Factors of significance for mobility in children with myelomeningocele.

AIM: To investigate neurological impairment, hand function and cognitive function in a group of children with myelomeningocele, in order to identify factors of significance for independent mobility and the physical assistance required for mobility in daily activities. METHODS: The study material comprised 32 children, aged 6-11 y and without mental retardation. Mobility was assessed with the Pediatric Evaluation of Disability Inventory, scored as caregiver assistance. Statistical differences and correlations between the caregiver assistance scores and the selected variables were analysed. RESULTS: Nine children scored independent mobility. The independent children had better hand coordination (p = 0.004) and walking ability (p = 0.01), lower cele levels (p = 0.011), higher performance IQ (p = 0.027), better visuospatial function (p = 0.029) and executive function (p = 0.037) than the others. The caregiver assistance scores were lower for both the children with early and severe symptoms of brainstem dysfunction and the children with scoliosis. Statistically significant correlations were found between the need for caregiver assistance and reduced walking ability, high cele level, poor hand strength and coordination, visuospatial function, executive function and performance IQ. In the subgroup of children who needed a wheelchair or walking aids, hand strength was the only variable significantly correlated with caregiver assistance (r(s) = 0.703, p = 0.000). CONCLUSION: Most of the children were dependent on others in daily activities. Impaired hand function and cognitive function were significant for mobility, and this has implications for the therapy programme in children with myelomeningocele.

Activities of Daily Living↗
PubMed2001

Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease.

We tested whether increased concentrations of the acute-phase reactant fibrinogen correlate with pulmonary function and rate of chronic obstructive pulmonary disease (COPD) hospitalization. We measured plasma fibrinogen and forced expiratory volume in 1 s (FEV(1)), and assessed prospectively COPD hospitalizations in 8,955 adults from the Danish general population. Smokers with plasma fibrinogen in the upper and middle tertile (> 3.3 and 2.7-3.3 g/L) had 7% (95% confidence interval [CI]: 5-8%) and 2% (0-3%) lower percentage predicted FEV(1) than smokers with fibrinogen in the lower tertile (< 2.7 g/L). The equivalent decreases in nonsmokers were 6% (4-7%) and 0% (-1-2%), respectively. Individuals with plasma fibrinogen in the upper and middle tertile had COPD hospitalization rates of 93 and 60 compared with 52 per 10,000 person-years in individuals with fibrinogen in the lower tertile (log-rank: p < 0.001 and p = 0.31). After adjusting for age, body mass index, sex, pack-years, and recent respiratory infections, relative risks for COPD hospitalization were 1.7 (95% CI: 1.1-2.6) and 1.4 (0.9-2.1) in individuals with fibrinogen in the upper and middle versus lower tertile. In conclusion, elevated plasma fibrinogen was associated with reduced FEV(1) and increased risk of COPD. This could not be explained by smoking alone.

Adult↗
PubMed2001

Synthesis and characterization of fluorescent and photoactivatable MIP-1alpha ligands and interactions with chemokine receptors CCR1 and CCR5.

Photoaffinity and fluorescent analogues of the 70-amino acid chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) were designed, synthesized, characterized, and applied to probe MIP-1alpha interactions with the chemokine receptors CCR1 and CCR5. The photoactivatable MIP-1alpha ligand, BP-MIP-1alpha, and the fluorescent ligand, Flu-MIP-1alpha were prepared by selective chemical coupling of p-benzoylphenylthiocarbamyl or fluoresceinthiocarbamyl, respectively, at the N-terminus of MIP-1alpha. Both ligands BP-MIP-1alpha and Flu-MIP-1alpha retained high binding affinity and agonist potency at CCR1 and CCR5. Photoaffinity labeling of CCR1 and CCR5 receptors stably expressed in CHO cells resulted in specific covalent attachment of [(125)I]BP-MIP-1alpha and production of protein complexes of 54 and 48 kDa, respectively, on SDS-PAGE. This represents the first photo-cross-linking between a chemokine and its receptor. Flu-MIP-1alpha selectively labeled CCR1 or CCR5 receptors expressed in CHO cells and was used to characterize receptor binding domains. When bound to CCR1 or CCR5 receptors, the fluorescence signal of Flu-MIP-1alpha was quenched by collision with iodide indicating that the N-terminal end of MIP-1alpha is accessible to the solvent. These data strongly suggest that the N-terminal end of MIP-1alpha interacts with domains of CCR1 or CCR5 receptors located at the extracellular surface. The photoactivatable BP-MIP-1alpha described here should prove valuable for the identification of contact sites on receptors by photoaffinity labeling experiments.

Animals↗
PubMed2001

Fifteen-year follow-up of pulmonary function in individuals heterozygous for the cystic fibrosis phenylalanine-508 deletion.

BACKGROUND: In a cross-sectional study, we previously showed that cystic fibrosis phenylalanine-508 deletion (DeltaF508) heterozygosity may be overrepresented among individuals with asthma. OBJECTIVE: Using 15-year follow-up data from the Copenhagen City Heart Study, we now further explore this relationship. METHODS: As part of 3 surveys in 1976 to 1978, 1981 to 1983, and 1991 to 1994, we measured pulmonary function and asked all participants about asthma and pulmonary risk factors. RESULTS: There was no difference in annual decline in lung function between DeltaF508 heterozygotes and noncarriers overall; however, among individuals with familial asthma, the annual declines in FEV(1) and forced vital capacity (FVC) were 49 and 36 mL in DeltaF508 heterozygotes versus 24 and 17 mL in noncarriers (P =.01 and P =.12, respectively). Cross-sectionally based on triple measurements, FEV(1) and FVC in individuals aged 20 to 70 years were lower in heterozygous participants versus noncarriers (P =.02 and P =.004, respectively). The average reduction of FEV(1) and FVC in DeltaF508 heterozygotes versus noncarriers was 70 mL (P =.06) and 136 mL (P =.008). Finally, 10% of carriers reported asthma versus 7% of noncarriers (P =.02), resulting in an odds ratio of 2.0 (1.3-3.2) for asthma in DeltaF508 heterozygotes. CONCLUSION: Cystic fibrosis DeltaF508 heterozygotes may be overrepresented among individuals with asthma and may have poorer lung function than noncarriers. Furthermore, DeltaF508 heterozygosity in context with familial predisposition to asthma may be associated with a greater annual FEV(1) decline.

Adult↗
PubMed2001

Asymmetries in the processing of emotionally valenced words.

Earlier research has shown a valence dependent encoding asymmetry of emotional words (e.g., Pratto & John, 1991; White, 1996; Stenberg, Wiking & Dahl, 1998). To further study this asymmetry, two word detection experiments were performed based on the following hypothesis: when there is a more thoroughly processing of the valence, in this case a valence categorisation, there will be, in a subsequent task, prolonged latencies for negative words, compared to positive words. The result gave significantly prolonged response latencies for negative words compared to positive ones in the subsequent detection task when using an affective orienting task, something not found using a non-affective orienting task. The results support the Mobilization-Minimization hypothesis (Taylor, 1991), according to which negative events and stimuli occupy more cognitive resources, but with some limitation: the affective asymmetry, with prolonged latencies for negative words, occurs only when there is a deepened encoding of the affective component of the words.

Analysis of Variance↗
PubMed2001

Molecular diagnosis of intermediate and severe alpha(1)-antitrypsin deficiency: MZ individuals with chronic obstructive pulmonary disease may have lower lung function than MM individuals.

BACKGROUND: We tested whether intermediate (MZ, SZ) and severe (ZZ) alpha(1)-antitrypsin deficiency affects lung function in the population at large. METHODS: We performed spirometry [forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)] and genotyping of 9187 individuals from the adult general population of Copenhagen, Denmark. RESULTS: As expected, the frequencies of individuals with MM, MS, SS, MZ, SZ, and ZZ genotypes were 0.891, 0.054, 0.001, 0.052, 0.001, and 0.001, respectively. Genotype interacted with clinically established chronic obstructive pulmonary disease (COPD) on the percentage of the predicted FEV(1) (P = 0. 004): the percentage of the predicted FEV(1) was reduced in MZ compared with MM individuals among those with clinically established COPD, but not among those without COPD. Furthermore, SZ compound heterozygotes had lower FEV(1)/FVC ratios than MM individuals (P <0.05), and ZZ homozygotes had lower percentages of the predicted FEV(1) and FEV(1)/FVC ratios than MM, MS, SS, and MZ individuals (all Ps <0.01). Reduced lung function in SZ and ZZ vs MM individuals could be demonstrated in current and ex-smokers, but not in nonsmokers. Compared with MM individuals in the same groups, FEV(1) was reduced 655 mL in MZ individuals with clinically established COPD, 364 mL in SZ current smokers, and 791 mL in ZZ current smokers. CONCLUSIONS: In the population at large, MZ was associated with reduced pulmonary function in individuals with clinically established COPD, whereas SZ and ZZ were associated with reduced pulmonary function in smokers. The presence of the alpha(1)-antitrypsin MZ genotype may in certain circumstances produce marked aggravation of airway obstruction in individuals prone to develop COPD.

Adult↗