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Sökning: WFRF:(Melander O) > (2005-2009)

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1.
  • Newton-Cheh, Christopher, et al. (författare)
  • Genome-wide association study identifies eight loci associated with blood pressure
  • 2009
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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2.
  • Bengtsson Boström, Kristina, et al. (författare)
  • Interaction between the angiotensin-converting enzyme gene insertion/deletion polymorphism and obstructive sleep apnoea as a mechanism for hypertension.
  • 2007
  • Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 1473-5598. ; 25:4, s. 779-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Obstructive sleep apnoea (OSA) confers a risk of hypertension and cardiovascular complications. Both the renin-angiotensin-aldosterone system and OSA are important determinants of blood pressure, but it is not fully known how they interact. The aim of this study was to explore the interaction between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and OSA in the association with hypertension. Design A community-based, case-control design with hypertensive patients in primary care (n =157) and normotensive population controls (n =181). Methods All subjects underwent ambulatory polysomnography during one night. OSA was defined by a minimum of 10 apnoea/hypopnoea events per hour. Office blood pressure was measured and hypertension status was assessed. The genotypes were determined using polymerase chain reaction. Results An interaction analysis including sex, ACE I/D polymorphism (DD and ID versus II), and OSA identified a significant interaction between OSA and the ACE I/D f polymorphism: odds ratio (OR) 6.3, 95% confidence interval (Cl) 1.8-22.5, P= 0.004 as well as between OSA and sex: OR 3.3, 95% Cl 1.1-9.6, P= 0.033. OSA was significantly associated with hypertension in men but not in women. Conclusion The interaction between the ACE gene I/D polymorphism and OSA appears to be an important mechanism in the development of hypertension, particularly in men.
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3.
  • Fava, Cristiano, et al. (författare)
  • Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes
  • 2007
  • Ingår i: DNA Sequence. - : Harwood Academic. - 1029-2365 .- 1042-5179. ; 18:5, s. 395-399
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Gitelman's syndrome (GS) is an inherited autosomal recessive disorder due to loss of function mutations in the SLC12A3 gene encoding the Na-Cl co-transporter (NCCT), the target of thiazide diuretics. The defective function of the NCCT, which normally is expressed in the apical membrane of the distal convolute tubule in the kidney, leads to mild hypotension, hypokalemia, hyperreninemic hyperaldosteronism, mild metabolic alkalosis, hypomagnesemia and hypocalciuria. Up to now, more than 100 mutations of the SLC12A3 gene have been described in GS patients. METHODS: We have collected 30 patients from Sweden with a clinical diagnosis of GS and undertaken a mutation screening by SSCP and successive sequencing of the 26 exons and intronic boundaries. Both mutations were identified in most (n = 28, 93%) and at least one mutation was identified in all patients. RESULTS: We found 22 different mutations evenly distributed throughout the gene, 11 of which have not been described previously. The new variants include 8 missense mutations (Glu68Lys, His69Asn, Argl45His, Vall53Met, Gly230Asp, Gly342Ala, Val677Leu and Gly867Ser), 1 insertion (c.834_835insG on exon 6) and 2 splice-site mutations (c.2667 + lT>G substitution in splicing donor site after exon 22, c.1569-1G>A substitution in the splicing acceptor site before exon 13). CONCLUSION: In Swedish patients with the clinical features of GS, disease-causing mutations in the SLC12A3 gene were identified in most patients. The spectrum of GS mutations is wide making full mutation screening of the SLC12A3 gene necessary to confirm the diagnosis.
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4.
  • Fava, Cristiano, et al. (författare)
  • Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure
  • 2008
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 17:3, s. 413-418
  • Tidskriftsartikel (refereegranskat)abstract
    • Gitelmans syndrome (GS) is an inherited recessive disorder caused by homozygous or compound heterozygous loss of function mutations of the NaCl cotransporter (NCCT) gene encoding the kidney-expressed NCCT, the pharmacological target of thiazide diuretics. An observational study estimated the prevalence of GS to 19/1 000 000, in Sweden, suggesting that similar to 1% of the population carries one mutant NCCT allele. As the phenotype of GS patients, who always carry two mutant alleles, is indistinguishable from that seen in patients treated with high-dose thiazide diuretics, we aimed at investigating whether subjects carrying one mutated NCCT allele have a phenotype resembling that of treatment with low-dose thiazide diuretics. We screened first-degree relatives of 18 of our patients with an established clinical end genetic diagnosis of GS for NCCT loss of function mutations and identified 35 healthy subjects carrying one mutant allele (GS-heterozygotes). Each GS-heterozygote was assigned a healthy control subject matched for age, BMI and sex. GS-heterozygotes had markedly lower blood pressure (systolic 103.3 +/- 16.4 versus 123.2 +/- 19.4 mmHg; diastolic 62.5 +/- 10.5 versus 73.1 +/- 9.4 mmHg; P < 0.001) than controls. There was no significant difference between the groups either in plasma concentration or urinary excretion rate of electrolytes, however, GS-heterozygotes had higher fasting plasma glucose concentration. Similar to patients being treated with low-dose thiazide diuretics, GS-heterozygotes have markedly lower blood pressure and slightly higher fasting plasma glucose compared with control subjects. Our findings suggest that GS-heterozygotes, the prevalence of which can be estimated to 1%, are partially protected from hypertension through partial genetic loss of function of the NCCT. However, as our study had a case-control design, it is important to underline that any potential effects on population blood pressure and risk of future cardiovascular disease need to be examined in prospective and population-based studies.
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5.
  • Kathiresan, S., et al. (författare)
  • Polymorphisms associated with cholesterol and risk of cardiovascular events
  • 2008
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 358:12, s. 1240-1249
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Common single-nucleotide polymorphisms (SNPs) that are associated with blood low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol modestly affect lipid levels. We tested the hypothesis that a combination of such SNPs contributes to the risk of cardiovascular disease. Methods: We studied SNPs at nine loci in 5414 subjects from the cardiovascular cohort of the Malmo Diet and Cancer Study. We first validated the association between SNPs and either LDL or HDL cholesterol and subsequently created a genotype score on the basis of the number of unfavorable alleles. We used Cox proportional-hazards models to determine the time to the first cardiovascular event in relation to the genotype score. Results: All nine SNPs showed replication of an association with levels of either LDL or HDL cholesterol. With increasing genotype scores, the level of LDL cholesterol increased from 152 mg to 171 mg per deciliter (3.9 to 4.4 mmol per liter), whereas HDL cholesterol decreased from 60 mg to 51 mg per deciliter (1.6 to 1.3 mmol per liter). During follow-up (median, 10.6 years), 238 subjects had a first cardiovascular event. The genotype score was associated with incident cardiovascular disease in models adjusted for covariates including baseline lipid levels (P<0.001). The use of the genotype score did not improve the clinical risk prediction, as assessed by the C statistic. However, there was a significant improvement in risk classification with the use of models that included the genotype score, as compared with those that did not include the genotype score. Conclusions: A genotype score of nine validated SNPs that are associated with modulation in levels of LDL or HDL cholesterol was an independent risk factor for incident cardiovascular disease. The score did not improve risk discrimination but did modestly improve clinical risk reclassification for individual subjects beyond standard clinical factors.
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6.
  • Mölstad, S., et al. (författare)
  • Sustained reduction of antibiotic use and low bacterial resistance : 10-year follow-up of the Swedish Strama programme
  • 2008
  • Ingår i: Lancet. Infectious diseases (Print). - : Institutionen för klinisk och experimentell medicin. - 1473-3099 .- 1474-4457. ; 8:2, s. 125-132
  • Forskningsöversikt (refereegranskat)abstract
    • Increasing use of antibiotics and the spread of resistant pneumococcal clones in the early 1990s alarmed the medical profession and medical authorities in Sweden. Strama (Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance) was therefore started in 1994 to provide surveillance of antibiotic use and resistance, and to implement the rational use of antibiotics and development of new knowledge. Between 1995 and 2004, antibiotic use for outpatients decreased from 15.7 to 12.6 defined daily doses per 1000 inhabitants per day and from 536 to 410 prescriptions per 1000 inhabitants per year. The reduction was most prominent in children aged 5-14 years (52%) and for macrolides (65%). During this period, the number of hospital admissions for acute mastoiditis, rhinosinusitis, and quinsy (peritonsillar abscess) was stable or declining. Although the epidemic spread in southern Sweden of penicillin-resistant Streptococcus pneumoniae was curbed, the national frequency increased from 4% to 6%. Resistance remained low in most other bacterial species during this period. This multidisciplinary, coordinated programme has contributed to the reduction of antibiotic use without measurable negative consequences. However, antibiotic resistance in several bacterial species is slowly increasing, which has led to calls for continued sustained efforts to preserve the effectiveness of available antibiotics.
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7.
  • Amisten, Stefan, et al. (författare)
  • The P2Y(13) Met-158-Thr Polymorphism, Which Is in Linkage Disequilibrium with the P2Y(12) Locus, Is Not Associated with Acute Myocardial Infarction.
  • 2008
  • Ingår i: PLoS ONE. - : Public Library of Science. - 1932-6203. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: The aims of this study were to investigate (1) if P2Y(12) polymorphisms defining the P2Y(12) H2 allele are associated with any other SNPs that may explain the previously reported association with increased ADP induced platelet activation and association with peripheral arterial disease and coronary artery disease and (2) if such variants are associated with acute myocardial infarction (AMI) or classical risk factors for AMI. METHODS AND RESULTS: The P2Y(13) Met-158-Thr polymorphism was found to be in linkage disequilibrium (LD) with the P2Y(12) H2 haplotype (all examined SNPs: D' = 1.0, r(2) = 0.936-1.0), defining a novel P2Y(12) H2/P2Y(13) Thr-158 haplotype. Genotyping of an AMI case control population (n = 1244 cases, 2488 controls) revealed no association of the P2Y(13) Thr-158 allele with AMI (OR = 0.96, 95% C.I. 0.82-1.12, P = 0.63). Also, no differences between the genotype frequencies of P2Y(13) Met-158-Met and Met-158-Thr/Thr-158-Thr were seen in AMI case-control subpopulations (early onset AMI OR = 1.06, 95% C.I. 0.85-1.31, P = 0.62); family history of AMI (OR = 0.98, 95% C.I. 0.78-1.22, P = 0.83) nor in early onset AMIs with family history of AMI (OR = 1.0, 95% C.I. 0.74-1.36, P = 1.0). Genotyping of the P2Y(13) Met-158-Thr polymorphism in a population based sample (n = 6055) revealed no association with cardiovascular risk factors. In addition, the P2Y(13) Met-158-Thr polymorphism was genotyped in a diabetes case-control population, and associations were found neither with DM nor with any examined DM risk factors. CONCLUSION GENOTYPING: The P2Y(13) Met-158-Thr polymorphism is in tight LD with the P2Y(12) locus but is not associated with AMI or classical cardiovascular risk factors.
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8.
  • Andersson, K, et al. (författare)
  • Repeat prescriptions: refill adherence in relation to patient and prescriber characteristics, reimbursement level and type of medication
  • 2005
  • Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262. ; 15:6, s. 621-626
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Repeat prescribing used in long-term pharmacotherapy is often associated with inadequate patient medication, including non-adherence. In this paper we explore patients' drug refill adherence with repeat prescriptions and relate refill data to patient age and gender, type of prescriber, type of prescribed drug, and reimbursement level. Methods: During one week of 2002, copies of 3636 repeat prescriptions filled at 16 large Swedish pharmacies were collected. Satisfactory refill adherence was defined as dispensed refills covering 80-120% of the prescribed treatment time. Under- and oversupplying were defined as < 80% and > 120% coverage, respectively. Result: The average level of refill adherence was 57%, and the level of under- and oversupplying 21% and 22%, respectively. There was no gender difference. Patients who were exempt from payment had higher oversupplies than others (33% versus 19%), and patients of general practitioners had higher refill adherence than patients of hospital physicians. The highest refill adherence was observed for contraceptives (81%) and the lowest for anti-asthmatics, proton pump inhibitors and non-steroidal anti-inflammatory drugs (30-40%). Conclusions: Refill non-adherence includes both under- and oversupplying and may vary due to different attitudes between prescribers and between patients. Different therapeutic indications and reimbursement systems are other apparent causes. These observations should be considered in programs aiming to assist patients in following medication prescriptions.
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10.
  • Fritzell, Emma, 1979, et al. (författare)
  • Drying kinetics and equilibrium moisture content of MDF fibres
  • 2009
  • Ingår i: Drying Technology. - 1532-2300 .- 0737-3937. ; 27:9, s. 993-998
  • Tidskriftsartikel (refereegranskat)abstract
    • An experimental device was constructed to study the drying kinetics of wood fibers under controlled conditions. The device consisted of a drying chamber in which a net basket filled with the fiber material was connected to a load cell. The drying medium was then forced through the basket at controlled levels of humidity and temperature. Experiments were performed with spruce fibers and the drying medium at varying temperature (50-170° C) and relative humidity (1-86%). In general, the drying rate increased with increasing temperature and decreasing relative humidity. A constant drying rate period was observed in all cases. The critical moisture content was approximately 1.25. The characteristic drying curve has a slight downward concave shape. The equilibrium moisture contents obtained at ambient temperature agree well with data in the literature. © 2009 Taylor & Francis Group, LLC.
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