| 1. |
- Bernspång, Elisabeth, et al.
(författare)
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CT lung densitometry in young adults with alpha-1-antitrypsin deficiency
- 2011
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 105:1, s. 74-79
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe (PiZZ) and moderate (PiSZ) alpha-1-antitrypsin (AAT) deficiency predispose to lung emphysema, especially in smokers. We hypothesized that multi-slice computed tomography (CT) might be superior to pulmonary function tests (PFT) to detect lung emphysema in AAT-deficient individuals at the age of 32 years. Methods: A subgroup of PiZZ and PiSZ individuals identified during the Swedish newborn screening programme in 1972-74 underwent multi-slice CT and PFT at the age of 32 years. From the CT scans the percentile density at 15% (PD15) and the relative area below -910 Hounsfield Units (RA(-910) HU) were calculated. The results of PFT and CT were compared between the AAT-deficient individuals and an age-matched control group. Results: Twenty-five PiZZ, 11 PiSZ and 17 PiMM individuals participated in the study. All Pi subgroups had normal lung function. The mean PD15 was 81 (SD 22) g/L in the PiZZ individuals, 96 (SD 35) g/L in the PiSZ individuals and 79 (SD 17) g/L in the PiMM individuals (ns), and the RA-910 were 30 (SD 18)%, 24 (SD 20)%, and 32 (SD 18)%, respectively (ns). For the never-smoker subgroups, in the PiZZ (n = 23), PiSZ (n = 8) and PiMM (n = 12), the mean PD15 were 95 (SD 35) g/L, 81 (SD 22) g/L, and 75 (SD 12) g/L, respectively (ns). PD15 was significantly correlated to CT derived lung size (r = -0.72; p < 0.001). Conclusions: CT densitometry revealed no signs of emphysema and no differences between the AAT-deficient individuals identified by neonatal screening and age-matched control subjects.
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| 2. |
- Bernspång, Elisabeth, et al.
(författare)
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Lung function in 30-year-old alpha-1-antitrypsin-deficient individuals.
- 2009
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 103, s. 861-865
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alpha-1-antitrypsin (AAT) deficiency increases the risk of emphysema, especially in smokers. In 1972-1974, all 200,000 Swedish new-born infants were screened for AAT deficiency and individuals with severe (PiZZ) and moderate (PiSZ) deficiency have been followed-up regularly. The aim of the present study was to examine their lung function at the age of 30years, comparing them to a group of age-matched control subjects (PiMM) recruited from the general population, and to compare current smokers with never-smokers. METHOD: Static and dynamic spirometry, including TLC, FRC, RV, VC, FEV(1,)K(CO) and D(L,CO), was performed for all participants. All values were expressed as percentages of the expected values. FEV(1)/VC was expressed both as percentage of the expected value and in absolute numbers. RESULTS: Four of 60 PiZZ, none of 19 PiSZ and 9 of 33 PiMM participating individuals were current smokers. All Pi groups had a normal mean FEV(1). The mean (SD) FEV(1)/VC ratio was 75% (7.4) in the PiZZ smokers and 84% (5.5) in the PiZZ never-smokers (p<0.01). The mean (SD) K(CO) was 81 (13) in the PiZZ smokers and 99 (14) in the PiZZ never-smokers (p<0.05). CONCLUSION: AAT-deficient individuals identified by neonatal screening have normal lung function at the age of 30. The PiZZ smokers had changes in lung function that may be signs of early emphysema.
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| 3. |
- Bernspång, Elisabeth, et al.
(författare)
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Respiratory symptoms and lung function in 30-year-old individuals with alpha-1-antitrypsin deficiency.
- 2007
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 101, s. 1971-1976
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Individuals with severe alpha-1-antitrypsin (AAT) deficiency have a well-known risk of developing emphysema but it is not known at which age the first symptoms occur and lung function declines. The aim of this study was to examine the prevalence of smoking, respiratory symptoms and lung function at the age of 30 in AAT-deficient individuals (PiZ and PiSZ) identified by neonatal screening. Material and methods: One hundred and seven PiZ, 45 PiSZ and 197 control subjects (PiMM) filled in a questionnaire regarding smoking habits and symptoms. Ninety PiZ, 40 PiSZ and 84 control subjects underwent spirometry including FEV1 and FVC. Results: Twenty-one percent of PiZ, 23% of PiSZ and 34% of PiMM subjects had smoked at some time (p < 0.05). Sixty-five percent of PiZ, 55% of PiSZ and 35% of PiMM ever-smokers reported shortness of breath on exertion (p < 0.05 PiZ vs PiMM). The mean FEV1, was 101% predicted (95% CI 98-104) in PiZ, 101% predicted (95% CI 97-106) in PISZ, and 96% predicted (95% 93-98) in PiMM individuals (p < 0.05). There was no difference in mean FEV1 when comparing ever- and neversmokers in the different Pi groups separately. Conclusion: At the age of 30, the AAT-deficient individuals in this cohort report more symptoms than the control subjects. Smoking is less common in the cohort compared to controls. Their lung function is normal.
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| 4. |
- Ekström, Ulf, et al.
(författare)
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An efficient screening procedure detecting six novel mutations in the LDL receptor gene in Swedish children with hypercholesterolemia
- 1995
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Ingår i: Human Genetics. - 1432-1203. ; 96:2, s. 147-150
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Tidskriftsartikel (refereegranskat)abstract
- Familial hypercholesterolemia (FH) is an autosomal semi-dominant disorder caused by defects in the low density lipoprotein receptor (LDLR) gene and is a well-documented risk factor for developing cardiovascular disease. The LDLR genes of five Swedish children with FH were examined in this study. Initial mutation screening was performed by denaturing gradient gel electrophoresis (DGGE) with enzymatically amplified exon-sized fragments, each containing a tailing GC-rich requence. The GC-clamped fragments had been synthesized with a restriction site adjacent to the intron-corresponding sequence to allow detachment of the clamps, thereby rendering the fragments suitable for subsequent analysis by single-strand conformation polymorphism (SSCP) analysis of samples from patients with no DGGE-detectable mutations. In addition, all the LDLR genes of the patients were screened for large alterations by restriction fragment length polymorphism analysis. Following this strategy, seven different, potentially disease-causing mutations were detected in the five children with FH. Six of the alterations, five single-base substitutions and one dinucleotide deletion, have not previously been described. DGGE detected six of the mutations and SSCP the seventh.
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| 5. |
- Ekström, Ulf, et al.
(författare)
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Expression of an LDL receptor allele with two different mutations (E256K and I402T)
- 2000
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Ingår i: Molecular Pathology. - 1366-8714. ; 53:1, s. 31-36
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To investigate the disease causing event in patients with familial hypercholesterolaemia, carrying two mutations each, E256K in exon 6 and I402T in exon 9, of the gene encoding the low density lipoprotein (LDL) receptor. It was not known whether the mutations were positioned in cis or trans, or if they were each pathogenic separately or only when present together. METHODS: Polymerase chain reaction, denaturing gradient gel electrophoresis and sequencing were used to characterise the LDL receptor locus of the patients and family members. The different LDL receptor mutants, constructed in vitro by oligonucleotide directed mutagenesis, were expressed in LDL receptor deficient Chinese hamster ovary (CHO1d1A7) cells, to determine the effects of the mutations on LDL receptor function. RESULTS: The two mutations were located on the same allele of the LDL receptor gene. All mutant constructs resulted in the production of a detectable protein in CHO cells. The cells expressing only the I402T mutation, or the combination of I402T and E256K mutations, were seriously affected in mediating uptake and degradation of LDL. Contrary to initial predictions, the cells expressing only the E256K mutation showed essentially the same binding, uptake, and degradation of 125I labelled LDL as cells transfected with normal LDL receptor cDNA. These results suggest that the pathogenic mutation in the patients heterozygous for the E256K/I402T allele is the I402T mutation, and that E256K alone is a rare sequence variation, which does not affect LDL receptor protein function. E256K was not detected either in DNA from a healthy population or in DNA from other hypercholesterolaemic patients studied. CONCLUSIONS: Despite the information available on the structure-function relations between the LDL receptor and LDL receptor like proteins, predictions about the disease causing potential of a mutation are not reliable. These results suggest that the I402T mutation is pathogenic and that the substitution of E256K alone is a rare sequence variation, without a detectable phenotype modulating effect.
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| 6. |
- Flodmark, Carl-Erik, et al.
(författare)
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Prevention of progression to severe obesity in a group of obese schoolchildren treated with family therapy
- 1993
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Ingår i: Pediatrics. - 1098-4275. ; 91:5, s. 880-884
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVE. To evaluate the effect of family therapy on childhood obesity. DESIGN. Clinical trial. One year follow-up. SETTING. Referral from school after screening. PARTICIPANTS. Of 1774 children (aged 10 to 11), screened for obesity, 44 obese children were divided into two treatment groups. In an untreated control group of 50 obese children, screened in the same manner, body mass index (BMI) values were recorded twice, at 10 to 11 and at 14 years of age. INTERVENTION. Both treatment groups received comparable dietary counseling and medical checkups for a period of 14 to 18 months, while one of the groups also received family therapy. RESULTS. At the 1-year follow-up, when the children were 14 years of age, intention- to-treat analyses were made of the weight and height data for 39 of 44 children in the two treatment groups and for 48 of the 50 control children. The increase of BMI in the family therapy group was less than in the conventional treatment group at the end of treatment, and less than in the control group (P = .04 and P = .02, respectively). Moreover, mean BMI was significantly lower in the family therapy group than in the control group (P < .05), and the family therapy group also had fewer children with BMI > 30 than the control group (P = .02). The reduction of triceps, subscapular, and suprailiac skinfold thicknesses, expressed as percentages of the initial values, was significantly greater in the family therapy group than in the conventional treatment group (P = .03, P = .005 and P = .002, respectively), and their physical fitness was significantly better (P < .05). CONCLUSIONS. Family therapy seems to be effective in preventing progression to severe obesity during adolescence if the treatment starts at 10 to 11 years of age.
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| 7. |
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| 8. |
- Flodmark, Carl-Erik, et al.
(författare)
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Waist measurement correlates to a potentially atherogenic lipoprotein profile in obese 12-14-year-old children
- 1994
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 83:9, s. 941-945
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have indicated a relationship between overweight and cardiovascular disease. The present investigation was undertaken to identify anthropometric variables in childhood which may reflect the risk of cardiovascular disease in terms of unfavourable changes in apolipoprotein and lipid concentrations. Twenty-nine obese 14-year-olds and 32 obese 12-year-olds were recruited from a school screening programme and anthropometric data reflecting overweight and fat distribution were subjected to analysis of covariance, with blood pressure, apolipoprotein and lipid concentrations as dependent variables. Results from the two groups were adjusted for puberty, gender and screening group, allowing pooling of data. After such an adjustment, waist circumference was significantly correlated (r = partial correlation coefficient) to high density lipoprotein (HDL) cholesterol (r = -0.08, p < 0.05) and triglycerides (r = +0.24, p < 0.01). The waist:hip ratio was significantly correlated to HDL-cholesterol (r = -0.10, p < 0.01) and triglycerides (r = +0.22, p < 0.01). BMI was significantly correlated to triglycerides (r = +0.25, p < 0.001), and diastolic blood pressure (r = +0.08, p < 0.05). The partial regression coefficients for waist circumference versus apolipoprotein B (r = +0.07) and the apolipoprotein B:A-I ratio (r = +0.06) were as strong as those for waist:hip ratio (r = +0.03 and r = +0.05, respectively). Our results demonstrate that abdominal obesity is associated with an unfavourable lipid profile in obese 12-14-year-old children. This may be related to an increased cardiovascular risk later in life. The waist measurement appears to be a convenient and informative anthropometric indicator of such metabolic alterations.
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| 9. |
- Granquist, Å, et al.
(författare)
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A longitudinal cohort study on the prevalence of Helicobacter pylori antibodies in Swedish children and adolescents.
- 2002
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Ingår i: Acta Pædiatrica. - 1651-2227. ; 91:6, s. 636-640
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to monitor the Helicobacter pylori antibody seroprevalence of an asymptomatic cohort between the ages of 4 and 18 y. The H. pylori antibody titres in a longitudinally followed cohort of 168 native Swedish children (born between 1972 and 1974) were established at 4, 8, 12, 16, and 18 y of age. Seventeen children (10.1%) were found positive on at least one occasion when a paediatric cut-off was applied. Five children (3.0%) reached levels considered positive in adults. The seroprevalence at 4 y of age was 4.0%, at 8 y 2.5%, at 12 y 4.9%, at 16 y 5.3%, and at 18 y 6.3%. The difference in serological titres between the age groups was not significant. A change from negative to positive after the age of 4 took place in 5 of the cases. Spontaneous seroreversion appeared in 5 cases. CONCLUSION: Our findings showed no significant differences among the various age groups. Seventeen of the 168 children (10.1%) had been infected at some time, the prevalence ranging from 2.5% to 6.3%. Seroconversion and seroreversion occurred infrequently between the ages of 4 and 18 y.
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| 10. |
- Janciauskiene, Sabina, et al.
(författare)
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Performance of enhanced liver fibrosis plasma markers in asymptomatic individuals with ZZ α1-antitrypsin deficiency.
- 2011
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Ingår i: European Journal of Gastroenterology and Hepathology. - 1473-5687. ; 23:8, s. 716-720
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Alpha1-antitrypsin deficiency (AATD) is a common genetic cause of chronic liver disease. According to retrospective studies, up to 25% of those with homozygous ZZ (Glu 342 to Lys) AATD suffer from liver cirrhosis and/or liver cancer in late adulthood. We hypothesized that the plasma markers for liver fibrosis, necrosis, and apoptosis may identify AATD individuals at higher risk for liver diseases. METHODS: The study cohort included 52 clinically healthy ZZ AATD individuals of 34 years of age, identified in the Swedish neonatal screening of 1972-1974, and 81 age-matched controls with normal MM AAT variant. We analyzed plasma levels of the enhanced liver fibrosis (ELF) panel, including plasma tissue inhibitor of metalloprotease-1, amino-terminal propeptide of type III collagen and hyaluronic acid (HA), and the M30 and M65 antigens, markers for apoptosis/necrosis. RESULTS: Higher levels of tissue inhibitor of metalloprotease-1 (52%, P<0.001), amino-terminal propeptide of type III collagen (12%, P<0.05), HA (17% not significant), and M65 (13.4%, P=0.043) were found in ZZ than in MM patients. In the ZZ group, plasma levels of AAT correlated with M65 (P<0.01) and with HA (P<0.05). On the basis of the ELF panel, M30 and M65, a logistic regression model enabled us to correctly classify 81.2% of the originally grouped ZZ and MM cases with a sensitivity of 73.1% and a specificity of 86.4%. CONCLUSION: The ELF markers are associated with ZZ AATD at early adulthood, and can be considered as a useful tool to identify ZZ cases at an increased risk of developing liver diseases later in life.
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