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M Dahl

Publications and source records attributed to M Dahl.

At least 55 records · Page 3Linked to original sources

Chronic lung injury in preterm lambs: abnormalities of the pulmonary circulation and lung fluid balance.

Chronic lung disease of early infancy, or bronchopulmonary dysplasia, is a frequent complication of prolonged mechanical ventilation after premature birth. Pulmonary hypertension and edema are common features of this condition, which is often attributed to long-term, repetitive overinflation of incompletely developed lungs. The overall objective of this work was to examine the effects on the pulmonary circulation and lung fluid balance of different ventilation strategies using large versus small inflation volumes in an animal model of bronchopulmonary dysplasia. We studied 16 newborn lambs that were delivered prematurely (124+/-3 d gestation, term = 147 d) by cesarean section and mechanically ventilated for 3 to 4 wk. Ten lambs were ventilated at 20 breaths/min, yielding a tidal volume of 15+/-5 mL/kg, and six lambs were ventilated at 60 breaths/min, yielding a tidal volume of 6+/-2 mL/kg. All lambs received surfactant at birth and had subsequent surgery for closure of the ductus arteriosus and catheter placement to allow serial measurements of pulmonary vascular resistance and lung lymph flow. Chronic lung injury, documented by serial chest radiographs and postmortem pathologic examination, developed in all lambs irrespective of the pattern of assisted ventilation. Pulmonary vascular resistance, which normally decreases during the month after birth at term, did not change significantly from the first to the last week of study. Lung lymph flow, an index of net transvascular fluid filtration, increased with time in lambs that were ventilated at 20 breaths/min, but not in lambs ventilated at 60 breaths/min. Lymph protein concentration decreased with time, indicative of increased fluid filtration pressure, without evidence of a change in lung vascular protein permeability. Postmortem studies showed interstitial lung edema, increased pulmonary arteriolar smooth muscle and elastin, decreased numbers of small pulmonary arteries and veins, and decreased capillary surface density in distal lung of chronically ventilated lambs compared with control lambs that were killed either 1 d (same postconceptional age) or 3 wk (same postnatal age) after birth at term. Thus, chronic lung injury from prolonged mechanical ventilation after premature birth inhibits the normal postnatal decrease in pulmonary vascular resistance and leads to lung edema from increased fluid filtration pressure. These abnormalities of the pulmonary circulation may contribute to the abnormal respiratory gas exchange that often exists in infants with bronchopulmonary dysplasia.

Animals↗

[Carriers of cystic fibrosis are more susceptible to asthma. The Osterbro study].

We tested the hypothesis that individuals heterozygous for the common cystic fibrosis delta F508 mutation are at risk of obstructive pulmonary disease. We studied a cross-sectional sample from the general population of Copenhagen, aged 20 years and older. We performed spirometry to measure FEV1 and FVC, and genotyped blood samples from 9141 individuals. We identified 250 carriers of the delta F508 mutation (2.7%; 95% CI: 2.5%-3.1%). Nine precent of carriers reported having asthma compared with 6% of non-carriers (chi 2: p = 0.04). Furthermore, among individuals with airway obstruction, the percentage of predicted FEV1 and FVC were significantly lower in participants heterozygous for delta F508 than in non-carriers (49% vs. 58%, p = 0.004 and 70% vs. 82%, p < 0.001, respectively). Cystic fibrosis delta F508 heterozygosity may be over-represented among people with asthma and seems to be associated with decreased pulmonary function in people with airway obstruction who also have asthma.

Adult↗

[Metaphyseal chondrodysplasia].

Metaphyseal chondrodysplasia (MCD) is a heterogeneous group of diseases characterised by defective enchondral ossification, leading to metaphyseal changes. The different types of MCD can be distinguished by clinical findings, radiology and genetic tests. Based on a case story with MCD, pancreatic insufficiency and granulocytopenia (Shwachman's syndrome), we review the most common types of MCD with regard to clinical manifestations, radiological findings, and genetic background.

Adolescent↗

A role for Ctr9p and Paf1p in the regulation G1 cyclin expression in yeast.

Entry into the cell cycle in budding yeast involves transcriptional activation of G1cyclin genes and DNA synthesis genes when cells reach a critical size in late G1. Expression of G1cyclins CLN1 and CLN2 is regulated by the transcription factor SBF (composed of Swi4p and Swi6p) and depends on the cyclin-dependent Cdc28 protein kinase and cyclin Cln3p. To identify novel regulators of SBF-dependent gene expression we screened for mutants that fail to activate transcription of G1cyclins. We found mutations in a gene called CTR9. ctr9 mutants are inviable at 37 degrees C and accumulate large cells. CTR9 is identical to CDP1. CTR9 encodes a conserved nuclear protein of 125 kDa containing several TPR repeats implicated in protein-protein interactions. We show that Ctr9p is a component of a high molecular weight protein complex. Using immuno-affinity chromatography we found that Ctr9p associates with polypeptides of 50 and 65 kDa. By mass spectrometry these were identified as Cdc73p and Paf1p. We show that Paf1p, like Ctr9p, is required for efficient CLN2 transcription, whereas Cdc73p is not. Paf1p and Cdc73p were previously reported to be RNA poly-merase II-associated proteins, suggesting that the Ctr9p complex may interact with the general transcription apparatus.

Cell Cycle↗

Very preterm birth, birth trauma, and the risk of anorexia nervosa among girls.

BACKGROUND: Obstetrical complications, based on parental recall, have been reported to be associated with development of anorexia nervosa. We used prospectively collected data about pregnancy and perinatal factors to examine the subsequent development of anorexia nervosa. METHODS: This population-based, case-control study was nested in cohorts defined by all liveborn girls in Sweden from 1973 to 1984. From the Swedish Inpatient Register, 781 girls had been discharged from any hospital in Sweden with a main diagnosis of anorexia nervosa at the age of 10 to 21 years. For each case, 5 controls were randomly selected, individually matched by year and hospital of birth (n = 3905). Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for potential risk factors. RESULTS: Increased risk of anorexia nervosa was found for girls with a cephalhematoma (OR, 2.4; 95% CI, 1.4-4.1) and for very preterm birth (< or = 32 completed gestational weeks) (OR, 3.2; 95% CI, 1.6-6.2). In very preterm births, girls who were small for gestational age faced higher risks (OR, 5.7; 95% CI, 1.1-28.7) than girls with higher birth weight for gestational age (OR, 2.7; 95% CI, 1.2-5.8). CONCLUSIONS: Our results show that perinatal factors, possibly reflecting brain damage, had independent associations with anorexia nervosa. These risk factors may uncover the mechanisms underlying the development of the disorder, even if only a fraction of cases of anorexia nervosa may be attributable to perinatal factors.

Adolescent↗

Green fluorescent protein (GFP) as a marker during pollen development.

The transient expression of three mutant forms of green fluorescent protein (GFP) genes, GFP4, GFP5ER, and GFP4S65C, under several constitutive and pollen-specific promoters throughout pollen development in Nicotiana tabacum, Arabidopsis thaliana and Antirrhinum majus is described. Immature pollen of tobacco, Arabidopsis and snapdragon, isolated at different developmental stages, were bombarded with plasmids containing the GFP and cultured in vitro for several days until maturity. The expression of GFP was monitored every day during in vitro maturation, germination and pollination, as well as after in situ pollination. The expression pattern of each GFP construct was compared in parallel experiments to that of beta-glucuronidase (GUS) constructs expressed by the same promoters. The results show that the expression level of all three GFP mutant forms was dependent on the strength of the promoter used. The strongest promoter was the DC3 promoter, and no notable differences in the intensity and brightness of all three versions of GFP were observed. GFP-expressing pollen from tobacco and snapdragon developed in vitro for several days until maturity and germinated in vitro as well as on the surface of stigmata, strongly suggesting that all three GFPs are not toxic for the development of functional pollen. Furthermore, stably transformed tobacco plants expressing GFP under the control of the strong pollen-expressed DC3 and LAT52 promoters were not impaired in reproductive function, confirming that GFP can be used as a non-destructive marker for plant reproductive biology and development.

Arabidopsis↗

[Allergic rhinoconjunctivitis treated with intramuscular injection of glucocorticoid].

Effects and side effects of injectable depot steroid in the treatment of allergic rhinoconjunctivitis (hay fever) are described. A few controlled studies have shown injectable steroids to be superior to the effect of placebo and locally applied steroid. Over a period of 10 years from 1984-95 only 26 registered side effects were reported to the central Danish register for side effects of drugs (Laegemiddelstyrelsens Bivirkningsregister). Only eight concerned subcutaneous atrophy and in two cases the cutaneous changes persisted. Based on registration of number of treatments in the county of Funen 1996, it is estimated that the use of injectable depot steroids for treatment of hay fever accounts for about 535,000 DDD (defined daily doses corresponding to about 33,000 treatments per year). We conclude that the use of injectable corticosteroids in the treatment of hay fever is common and effective and side effects are very rare. However, injectable corticosteroids should only be used when conventional treatment is not sufficient to control symptoms.

Betamethasone↗

DeltaF508 heterozygosity in cystic fibrosis and susceptibility to asthma.

BACKGROUND: Cystic fibrosis is a recessive disorder mainly characterised by lung disease. We tested the hypothesis that individuals heterozygous for the common cystic fibrosis deltaF508 mutation are at risk of obstructive pulmonary disease. METHODS: We studied a cross-sectional sample from the general population of Copenhagen, Denmark, aged 20 years and older. We did spirometry to measure forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), and did genotyping on blood samples of 9141 individuals. We asked all participants whether they had asthma, and asked for information on smoking and other factors that could have contributed to obstructive pulmonary disease. FINDINGS: We identified 250 carriers of the deltaF508 mutation (2.7% [95% CI 2.5-3.1]). 9% of carriers reported having asthma compared with 6% of non-carriers (p=0.04). The odds ratio for asthma in participants heterozygous for deltaF508 mutation was 2.0 (1.2-3.5, p=0.02). Furthermore, among individuals with airway obstruction, the percentage predicted FEV1 and FVC were significantly lower in participants heterozygous for deltaF508 than in non-carriers (49 vs 58%, p=0.004; and 70 vs 82%, p<0.001, respectively), mainly due to an effect in those with self-reported asthma. INTERPRETATION: Cystic fibrosis deltaF508 heterozygosity may be over-represented among people with asthma and seems to be associated with decreased pulmonary function in people with airway obstruction who also have asthma.

Asthma↗

Cystic fibrosis Delta F508 heterozygotes, smoking, and reproduction: studies of 9141 individuals from a general population sample.

Cystic fibrosis is the most common fatal autosomal recessive disease affecting Caucasian populations. It remains a puzzle how this disease is maintained at such a remarkably high incidence, however, it could be due to a reproductive advantage in cystic fibrosis heterozygotes. We tested this hypothesis. An adult Danish general population sample of 9141 individuals was screened for cystic fibrosis DeltaF508 heterozygotes; 250 carriers of this mutation were identified (2.7%). In the total sample DeltaF508 heterozygotes did not have more children than noncarriers; however, smoking interacted with genotype in predicting number of children (ANOVA: P < 0.001). Among nonsmokers, heterozygotes had more children than noncarriers (Wilcoxon: P = 0.03). Among smokers, the opposite was found: heterozygotes had fewer children than noncarriers (Wilcoxon: P = 0. 001). These findings remained significant after allowing for gender and the potential confounders of age, income, and education. Finally, after allowing for these covariates, number of children in DeltaF508 heterozygotes decreased with increasing extent of smoking (trend test: P = 0.003), while the opposite was true for noncarriers (trend test: P < 0.001). In conclusion, overall these results do not support a reproductive advantage for cystic fibrosis DeltaF508 heterozygotes. However, the data cannot totally exclude the possibility that nonsmoking DeltaF508 heterozygotes experience a reproductive advantage while smoking DeltaF508 heterozygotes experience the opposite, a reproductive disadvantage. Accordingly, the data suggest a previously undocumented role of smoking on fecundity among cystic fibrosis heterozygotes.

Adult↗

[Inhaled budesonide versus intramuscular dexamethasone in the treatment of pseudo-croup].

We randomised 59 children hospitalized for croup to treatment with either inhaled budesonide or injected dexamethasone. Group A were treated with two inhalations of 1000 micrograms budesonide and group B received dexamethasone 0.6 mg/kg intramuscularly. We used a modified Westley-score, based on chest-wall retractions, barking cough, respiratory frequency and stridor. The children was aged three months to six years (mean 20 months). Three hours after the first treatment there was significant improvement in score amongst all children (p < 0.001), but no difference between the two groups (p < 0.20). Six and 12 hours after the first treatment there were significantly better clinical scores in group B (p = 0.001, p = 0.0004). Based on this study we recommend dexamethasone 0.6 mg/kg intramuscularly for children to be treated for croup.

Administration, Inhalation↗

Liberty, anyone?

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Aging↗

Trends in serum lipid levels during 1980-1992 in children and young adults. The Cardiovascular Risk in Young Finns Study.

To assess secular trends in serum lipid levels in Finnish children and young adults, the authors examined a total of 3,517, 2,769, 2,392, 352, and 880 subjects who had complete data on serum lipids in 1980, 1983, 1986, 1989, and 1992, respectively, in a longitudinal follow-up study. Trend analyses were carried out among subjects aged 15 (n = 1,835) or 18 (n = 1,562) years to exclude the confounding effect of age on the study variables. Data on obesity, physical activity, smoking, and alcohol use were available from each study year, and data on diet were available for the study years 1980, 1986, and 1992. Between 1980 and 1992, mean total cholesterol levels decreased from 4.88 to 4.47 mmol/liter (from 189 to 173 mg/dl), and low density lipoprotein cholesterol levels decreased from 3.06 to 2.85 mmol/liter (from 119 to 110 mg/dl). The mean high density lipoprotein cholesterol levels decreased by 19%, from 1.43 to 1.15 mmol/liter (55.2 to 44.6 mg/dl). During 1986-1992, triglyceride levels increased by 15%, from 0.88 to 1.01 mmol/liter (78.2 to 89.9 mg/dl). During 1980-1992, body mass index values increased from 20.8 to 21.8 kg/m2, parallel to increases in skinfold thickness. In the diet, the ratio of polyunsaturated to saturated fatty acids increased from 0.26 to 0.39. Alcohol and oral contraceptive use became more frequent, and the subjects tended to become less physically active. In conclusion, a change in the lipid profile in Finnish adolescents aged 15 and 18 years and young adults during 1980-1992 was observed, characterized by a decrease in low density lipoprotein cholesterol and high density lipoprotein cholesterol levels and an increase in triglyceride level. Possible determinants for these changes include alterations in diet and a trend toward increased obesity.

Adolescent↗