| 1. |
- Hoieggen, A., et al.
(author)
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The impact of serum uric acid on cardiovascular outcomes in the LIFE study
- 2004
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In: Kidney Int. - 0085-2538. ; 65:3, s. 1041-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study demonstrated the superiority of a losartan-based regimen over atenolol-based regimen for reduction of cardiovascular (CV) morbidity and mortality. It has been suggested that the LIFE study results may be related to the effects of losartan on serum uric acid (SUA). SUA has been proposed as an independent risk factor for CV morbidity and death. METHODS: Cox regression analysis was used to assess relationship of SUA and treatment regimens with the LIFE primary composite outcome (CV death, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke). RESULTS: Baseline SUA was significantly associated with increased CV events [hazard ratio (HR) 1.024 (95% CI 1.017-1.032) per 10 micromol/L, P < 0.0001] in the entire study population. The association was significant in women [HR = 1.025 (1.013-1.037), P < 0.0001], but not in men [HR = 1.009 (0.998-1.019), P= 0.108]. After adjustment for Framingham risk score (FRS), SUA was no longer significant in the entire study population [HR = 1.006 (0.998-1.014), P= 0.122] or in men [HR = 1.006 (0.995-1.017), P= 0.291], but was significant in women [HR = 1.013 (1-1.025), P= 0.0457]. The baseline-to-end-of-study increase in SUA (standard deviation, SD) was greater (P < 0.0001) in atenolol-treated subjects (44.4 +/- 72.5 micromol/L) than in losartan-treated subjects (17.0 +/- 69.8 micromol/L). SUA as a time-varying covariate was strongly associated with events (P < 0.0001) in the entire population. The contribution of SUA to the treatment effect of losartan on the primary composite end point was 29% (14%-107%), P= 0.004. The association between time-varying SUA and increased CV risk tended to be stronger in women (P < 0.0001) than in men (P= 0.0658), although the gender-outcome interaction was not significant (P= 0.079). CONCLUSION: The increase in SUA over 4.8 years in the LIFE study was attenuated by losartan compared with atenolol treatment, appearing to explain 29% of the treatment effect on the primary composite end point. The association between SUA and events was stronger in women than in men with or without adjustment of FRS.
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| 2. |
- Ibsen, H., et al.
(author)
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Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE Study
- 2004
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In: Kidney Int Suppl. - 0098-6577. ; :92
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Journal article (peer-reviewed)abstract
- Studies have shown that albuminuria is associated with increased risk for cardiovascular events. We tested the relationship between albuminuria (UACR) and cardiovascular risk in 8206 hypertensive patients with left ventricular hypertrophy included in the LIFE Study. Follow-up was 39,122 patient years. The risk for the primary composite cardiovascular end point increases continuously from the lowest to the highest decile of baseline UACR. No specific threshold could be identified. In conclusion, albuminuria predicts the outcome in the LIFE Study. The risk for cardiovascular morbidity and mortality among hypertensive patients with left ventricular hypertrophy increases at much lower UACR than has been reported in diabetic patients.
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| 3. |
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| 4. |
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| 5. |
- Lewis, Cathryn M, et al.
(author)
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Genome scan meta-analysis of schizophrenia and bipolar disorder, part II : Schizophrenia
- 2003
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In: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 73:1, s. 34-48
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Journal article (peer-reviewed)abstract
- Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
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| 6. |
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| 7. |
- Okin, P. M., et al.
(author)
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Regression of electrocardiographic left ventricular hypertrophy during antihypertensive treatment and the prediction of major cardiovascular events
- 2004
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In: Jama. - 1538-3598. ; 292:19, s. 2343-9
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Journal article (peer-reviewed)abstract
- CONTEXT: Electrocardiographic left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular (CV) morbidity and mortality. However, the predictive value of changes in the magnitude of electrocardiographic LVH criteria during antihypertensive therapy remains unclear. OBJECTIVE: To test the hypothesis that lesser severity of electrocardiographic LVH during antihypertensive treatment is associated with decreased CV morbidity and mortality, independent of blood pressure levels and reduction and treatment modality. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, parallel-group study conducted in 1995-2001 among 9193 men and women with hypertension aged 55 through 80 years (mean, 67 years), with electrocardiographic LVH by Cornell voltage-duration product or Sokolow-Lyon voltage criteria and enrolled in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study. INTERVENTIONS: Losartan- or atenolol-based treatment regimens, with follow-up assessments for at least 4 (mean, 4.8 [SD, 0.9]) years. MAIN OUTCOME MEASURE: Composite end point of CV death, myocardial infarction (MI), or stroke in relation to severity of electrocardiographic LVH determined at baseline and on subsequent electrocardiograms obtained at 1 or more annual revisits. RESULTS: Cardiovascular death, nonfatal MI, or stroke occurred in 1096 patients (11.9%). In Cox regression models controlling for treatment type, baseline Framingham risk score, baseline and in-treatment blood pressure, and severity of baseline electrocardiographic LVH by Cornell product and Sokolow-Lyon voltage, less-severe in-treatment LVH by Cornell product and Sokolow-Lyon voltage were associated with 14% and 17% lower rates, respectively, of the composite CV end point (adjusted hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.82-0.90; P<.001 for every 1050-mm x ms [1-SD] decrease in Cornell product; and HR, 0.83; 95% CI, 0.78-0.88; P<.001 for every 10.5-mm [1-SD] decrease in Sokolow-Lyon voltage). In parallel analyses, lower Cornell product and Sokolow-Lyon voltage were each independently associated with lower risks of CV mortality (HR, 0.78; 95% CI, 0.73-0.83; P<.001; and HR, 0.80; 95% CI, 0.73-0.87; P<.001, respectively), MI (HR, 0.90; 95% CI, 0.82-0.98; P=.01; and HR, 0.90; 95% CI, 0.81-1.00; P = .04), and stroke (HR, 0.90; 95% CI, 0.84-0.96; P=.002; and HR, 0.81; 95% CI, 0.75-0.89; P<.001). CONCLUSIONS: Less-severe electrocardiographic LVH by Cornell product and Sokolow-Lyon voltage criteria during antihypertensive therapy is associated with lower likelihoods of CV morbidity and mortality, independent of blood pressure lowering and treatment modality in persons with essential hypertension. Antihypertensive therapy targeted at regression or prevention of electrocardiographic LVH may improve prognosis.
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| 8. |
- Brannvall, K, et al.
(author)
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Cystatin-B is expressed by neural stem cells and by differentiated neurons and astrocytes
- 2003
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In: Biochemical and Biophysical Research Communications - BBRC. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0006-291X .- 1090-2104. ; 308:2, s. 369-374
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Journal article (peer-reviewed)abstract
- Mutation in the gene encoding cystatin-B (CSTB) has been shown to cause progressive myoclonus epilepsy. Mice with a gene deletion of CSTB exhibit increased apoptosis of specific neurons but the physiological role of CSTB in brain cells is not fully understood. In the present study, we have examined the expression of CSTB in neural stem cells (NSC) and in differentiating mature brain cells. The results show that CSTB is present in embryonic and adult NSC and in the neuroepithelium. CSTB was expressed by both neurons and glial cells differentiated from NSC and in hippocampal cultures. CSTB localized mainly to the nucleus in NSC and in neurons, whilst in astrocytes CSTB was also in the cytoplasm. Double labeling showed that CSTB was present in the lysosomes in glial cells. The results demonstrate a nuclear expression of CSTB in NSC and in neurons, suggesting novel function for this molecule. (C) 2003 Elsevier Inc. All rights reserved.
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| 9. |
- Cavelier, L, et al.
(author)
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MtDNA mutations in maternally inherited diabetes : presence of the 3397 ND1 mutation previously associated with Alzheimer's and Parkinson's disease
- 2001
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In: Hereditas. - : Springer Science and Business Media LLC. - 0018-0661 .- 1601-5223. ; 135:1, s. 65-70
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Journal article (peer-reviewed)abstract
- Mutations in the mitochondrial tRNA(leu) (UUR) gene have been associated with diabetes mellitus and deafness. We screened for the presence of mtDNA mutations in the tRNA(leu) (UUR) gene and adjacent ND1 sequences in 12 diabetes mellitus pedigrees with a possible maternal inheritance of the disease. One patient carried a G to A substitution at nt 3243 (tRNA(leu) (UUR) gene) in heteroplasmic state. In a second pedigree a patient had an A to G substitution at nt 3397 in the ND1 gene. All maternal relatives of the proband had the 3397 substitution in homoplasmic state. This substitution was not present in 246 nonsymptomatic Caucasian controls. The 3397 substitution changes a highly conserved methionine to a valine at aa 31 and has previously been found in Alzheimer's (AD) and Parkinson's (PD) disease patients. Substitutions in the mitochondrial ND1 gene at aa 30 and 31 have associated with a number of different diseases (e.g. AD/PD, MELAS, cardiomyopathy and diabetes mellitus, LHON, Wolfram-syndrome and maternal inherited diabetes) suggesting that changes at these two codons may be associated with very diverse pathogenic processes. In a further attempt to search for mtDNA mutations outside the tRNAleu gene associated with diabetes, the whole mtDNA genome sequence was determined for two patients with maternally inherited diabetes and deafness. Except for substitutions previously reported as polymorphisms, none of the two patients showed any non-synonymous substitutions either in homoplasmic or heteroplasmic state. These results imply that the maternal inherited diabetes and deafness in these patients must result from alterations of nuclear genes and/or environmental factors.
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| 10. |
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| 11. |
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| 12. |
- Hartini, TNS, et al.
(author)
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Food pattern during economic crisis among pregnant women in Purworejo District, Central Java, Indonesia.
- 2003
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In: Food and Nutrition Bulletin. - 0379-5721 .- 1564-8265. ; 24:3, s. 256-267
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Journal article (peer-reviewed)abstract
- A cross-sectional study was conducted between 1996 and 1998. Six 24-hour recalls were performed during the second trimester of pregnancy among 450 women in Purworejo District, Central Java, Indonesia. The objectives of the study were to assess the food intake and food pattern among pregnant women before and during the economic crisis. Before the crisis, rich women had the highest intakes of animal foods, fats and oils, and sugar. Food intake among the urban poor and the rural landless poor subgroups was influenced by the emerging economic crisis. Although the price of rice increased, the intake of rice also increased among all subgroups. Rural poor women with access to rice fields increased their intake of rice and decreased their intake of nonrice staple foods (p < .05). There were significant decreases in the consumption of chicken by rich women and rural poor women with access to rice fields (p < .05). Rice was a strongly inferior good and remained an important supplier of energy, protein, and carbohydrate. Nuts and pulses were important suppliers of calcium and iron, and vegetables were an important supplier of vitamin A. Rich women increased their intake of nuts and pulses, vegetables, fats and oils, and sugar when their intake of rice increased (p < .05). The food patterns were based on rice, nuts and pulses, and vegetables, i.e., plant food. All but the rich women decreased their intake of nutritious foods such as meat, chicken, and fruits. The intake of nuts and pulses and of vegetables increased, whereas the intake of cooking oil and sugar remained constant.
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| 13. |
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| 14. |
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| 15. |
- Kern, M A, et al.
(author)
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Amyotrophic lateral sclerosis : Evidence for intact hepatocyte growth factor/MET signalling axis
- 2001
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In: Cytokine. - : W B SAUNDERS CO. - 1043-4666 .- 1096-0023. ; 15:6, s. 315-319
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Journal article (peer-reviewed)abstract
- Hepatocyte growth factor (HGF) is a secreted cytokine which is expressed in the central nervous system (CNS) together with its specific receptor MET. Since HGF exerts strong neurotrophic activity including motoneurons, we have further analysed whether the HGF/MET axis is defective in patients with amyotrophic lateral sclerosis (ALS). Intrathecal HGF-secretion was measured in cerebrospinal fluid (CSF) from patients with amyotrophic lateral sclerosis and in controls without neurological diseases using a specific sandwich immunoassay (ELISA). MET-expression was analysed by immunohistology in spinal cord cross-sections of ALS patients and unaffected controls. The HGF concentrations in CSF were moderately but significantly increased in ALS patients compared to healthy controls (580 pg/ml vs 348 pg/ml). MET-protein was detectable in spinal cord motoneurons of patients with ALS as well as unaffected controls. The data demonstrate that ALS does not show a lack of the trophic signalling axis, HGF/MET, suggesting that the signalling system itself is not affected. The moderate increase in HGF-secretion may represent a compensatory effect.
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| 16. |
- Montnemery, Peter, et al.
(author)
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Accuracy of a first diagnosis of asthma in primary health care.
- 2002
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In: Family Practice. - 1460-2229. ; 19:4, s. 365-368
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Journal article (peer-reviewed)abstract
- BACKGROUND: In a postal questionnaire study, the prevalence of asthma in southern Sweden has been found to be 5.5%. However, the register prevalence of asthma obtained from the medical records in the same municipality and age groups was found to be only 2.1%. OBJECTIVES: The aims of the study were to investigate whether the low register prevalence of asthma was caused by an underdiagnosis of asthma in primary health care and to validate a first diagnosis of asthma set by GPs in primary health care. METHODS: During a period of 3 months in 1997, all patients seeking care in the primary health care units of the municipality of Lund (population 171 877) with upper or lower airway infections, prolonged cough, allergic rhinitis, fatigue or a first positive diagnosis of asthma were recorded ( n = 3025). RESULTS: In the whole group of 3025 patients, 99 patients were found to have received a diagnosis of asthma for the first time during the study period. The diagnosis was verified in 52 of those 68 patients who attended a follow-up and examination by a respiratory physician. Among the remaining 2926 patients, 221 patients were selected randomly to constitute a control group. In this group, three patients were found to have asthma. Thus, the specificity of an asthma diagnosis set in primary health care was 0.99 [95% confidence interval (CI) 0.99-1.00] and the sensitivity was 0.59 (95% CI 0.31-0.81). CONCLUSIONS: The GPs in this study were good at excluding those who did not have asthma (specificity 99%) but less good in correctly diagnosing those who actually had current asthma (sensitivity 59%), which suggests an underdiagnosis of asthma.
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| 17. |
- Montnemery, Peter, et al.
(author)
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Familial related risk-factors in the development of chronic bronchitis/emphysema as compared to asthma assessed in a postal survey
- 2000
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In: European Journal of Epidemiology. - 1573-7284. ; 16:11, s. 1003-1007
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Journal article (peer-reviewed)abstract
- There is a lack of knowledge to which extent heredity or familial risk factors are involved in the development of chronic bronchitis/emphysema (CBE). Smoking is regarded as the most important risk factor, but only about 15% of smokers develop airway obstruction. We evaluated the importance of familial risk factors compared to smoking and ex-smoking using an epidemiological approach. In 1992, a postal questionnaire was distributed to a study sample. In all, 43 questions were asked, in a previously evaluated questionnaire, regarding respiratory symptoms, self-reported lung diseases, smoking habits and familial occurrence of chronic bronchitis and asthma. The questionnaire was sent to 12,073 adults living in the southernmost part of Sweden. The age range was 20-59 years with an equal gender distribution. The study sample was drawn from the population records. The questionnaire was answered by 8469 subjects (70.1%), of whom 392 subjects (4.6%) stated that they had or had had CBE and 469 subjects (5.5%) stated that they had or had had asthma. In a model with logistic regression using the five explanatory variables gender, age, familial occurrence for asthma, familial occurrence for CBE and current or ex-smoking the most important risk factors for CBE were familial occurrence for chronic bronchitis [Odds ratios (OR): 5.19, 95% confidence interval (CI): 4.09-6.60, p = 0.000] and current or ex-smoking (OR: 1.74, 95% CI: 1.41-2.14, p = 0.000). The most important risk factors for asthma were familial occurrence for asthma (OR: 3.71, 95% CI: 3.06-4.51, p = 0.000) and current or ex-smoking (OR: 1.33, 95% CI: 1.09-1.61, p = 0.004). We have found that familial occurrence for CBE in first degree relatives together with smoking is a stronger risk factor for the development of CBE than is smoking.
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| 18. |
- Montnemery, Peter, et al.
(author)
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Prevalence of obstructive lung diseases and respiratory symptoms in relation to living environment and socio-economic group
- 2001
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In: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 95:9, s. 744-752
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Journal article (peer-reviewed)abstract
- We wanted to test whether living environment, occupation and social position are risk factors for asthma and chronic bronchitis/emphysema (CBE). The prevalence of bronchial asthma, CBE, respiratory symptoms and smoking habits in a random sample of 12,071 adults aged 20-59 years was assessed in a postal survey with a slightly modified questionnaire previously used in central and northern Sweden (The OLIN studies). Occupation was coded according to a socio-economic classification system. Six different living environment areas were defined; city-countryside, seaside-not seaside and living close to heavy traffic-not living close to heavy traffic. Multiple logistic regression analysis (forward conditional) was applied to estimate the association between the proposed set of risk factors and self-reported obstructive lung diseases and lower respiratory symptoms controlling for age, gender and smoking. After two reminders, the response rate was 70.1% (n=8469); 33.8% of the responders were smokers. In all, 469 subjects (5.5%) stated that they had asthma and 4.6% reported CBE. Besides smoking, which was a risk for both asthma and CBE, there were different risk patterns for self-reported asthma and CBE. In the economically active population there was a tendency that CBE was more common among 'unskilled and semi-skilled workers'. This fact was further emphasized when the population was merged into the two groups 'low social position' and 'middle/high social position', with 'low social position' as a risk for CBE (OR=1.35, 95% CI=1.06-1.72). No social risk factors were identified for asthma. Living close to heavy traffic was a risk factor for asthma (OR=1.29, 95% CI=1.02-1.62) but not for CBE. Apart from this no living environmental risk factors for obstructive pulmonary diseases were identified. Asthma symptoms and long-standing cough were more common among those subjects living close to heavy traffic compared to those not living close to heavy traffic. To conclude, low social position was a risk factor for CBE and living close to heavy traffic was a risk factor for asthma.
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| 19. |
- Nihlén, Ulf, et al.
(author)
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Increased serum levels of carbohydrate-deficient transferrin in patients with chronic obstructive pulmonary disease
- 2001
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 61:5, s. 341-347
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The reason that only a minority of smokers develop chronic obstructive pulmonary disease (COPD) is still largely unknown. Glycosylation defects are involved in the pathological mechanisms in cystic fibrosis (CF), where chronic progressive obstructive lung disease dominates the clinical picture. Whether defects of protein glycosylation occur in COPD has not previously been examined. Increase in carbohydrate-deficient transferrin (CDT) in serum seems to function as an indicator of general defects of N-glycosylation. Recently, one study observed high serum CDT concentrations in CF patients. We examined whether subjects with COPD also have increased serum CDT levels. METHOD AND RESULTS: A total of 131 randomly selected individuals, 45-64 years of age, underwent a medical examination, spirometry and blood tests. Serum CDT was determined using high performance liquid chromatography. In subjects diagnosed as having COPD (n = 15), multiple logistic regression analyses demonstrated a significant relationship between the diagnosis of COPD and CDT, even after all efforts were made to take the influence of age and smoking into account (odds ratio 3.16, 95% CI 1.11-8.95). Also, in subjects with COPD there was an inverse partial correlation between forced expiratory volume in 1 s (FEV1) and serum CDT (r = -0.81, p = 0.001). CONCLUSION: These results suggest that protein glycosylation defects occur in COPD and, in addition, might be involved in the pathogenetic mechanisms of the disease. It seems that further investigation of the protein glycosylation in COPD is warranted.
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| 20. |
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