| 1. |
- Ng, M Y M, et al.
(author)
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Meta-analysis of 32 genome-wide linkage studies of schizophrenia
- 2009
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 14:8, s. 774-785
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Journal article (peer-reviewed)abstract
- A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.
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| 2. |
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| 3. |
- Bakhtadze, Ekaterine, et al.
(author)
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Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15-34 years) but not in middle-aged (40-59 years) diabetic patients
- 2008
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:12, s. 2224-2232
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Journal article (peer-reviewed)abstract
- Type 1 diabetes in children is characterised by autoimmune destruction of pancreatic beta cells and the presence of certain risk genotypes. In adults the same situation is often referred to as latent autoimmune diabetes in adults (LADA). We tested whether genetic markers associated with type 1 or type 2 diabetes could help to discriminate between autoimmune and non-autoimmune diabetes in young (15-34 years) and middle-aged (40-59 years) diabetic patients. In 1,642 young and 1,619 middle-aged patients we determined: (1) HLA-DQB1 genotypes; (2) PTPN22 and INS variable-number tandem repeat (VNTR) polymorphisms; (3) two single nucleotide polymorphisms (rs7903146 and rs10885406) in the TCF7L2 gene; (4) glutamic acid decarboxylase (GAD) and IA-2-protein tyrosine phosphatase-like protein (IA-2) antibodies; and (5) fasting plasma C-peptide. Frequency of risk genotypes HLA-DQB1 (60% vs 25%, p =9.4x10(-34); 45% vs 18%, p= 1.4x10(-16)), PTPN22 CT/TT (34% vs 26%, p=0.0023; 31% vs 23%, p=0.034), INS VNTR class I/I (69% vs 53%, p=1.3x10(-8); 69% vs 51%, p=8.5x10(-5)) and INS VNTR class IIIA/IIIA (75% vs 63%, p=4.3x10(-6); 73% vs 60%, p=0.008) was increased in young and middle-aged GAD antibodies (GADA)-positive compared with GADA-negative patients. The type 2 diabetes-associated genotypes of TCF7L2 CT/TT of rs7903146 were significantly more common in young GADA-negative than in GADA-positive patients (53% vs 43%; p=0.0004). No such difference was seen in middle-aged patients, in whom the frequency of the CT/TT genotypes of TCF7L2 was similarly increased in GADA-negative and GADA-positive groups (55% vs 56%). Common variants in the TCF7L2 gene help to differentiate young but not middle-aged GADA-positive and GADA-negative diabetic patients, suggesting that young GADA-negative patients have type 2 diabetes and that middle-aged GADA-positive patients are different from their young GADA-positive counterparts and share genetic features with type 2 diabetes.
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| 4. |
- Beeckman, Dimitri, et al.
(author)
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EPUAP classification system for pressure ulcers : european reliability study
- 2007
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In: Journal of Advanced Nursing. - 0309-2402 .- 1365-2648. - 0309-2402 ; 60:6, s. 682-691
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Journal article (peer-reviewed)abstract
- Aim. This paper is a report of a study of the inter-observer reliability of the European Pressure Ulcer Advisory Panel pressure ulcer classification system and of the differential diagnosis between moisture lesions and pressure ulcers. Background. Pressure ulcer classification is a valuable tool to provide a common description of ulcer severity for the purposes of clinical practice, audit and research. Despite everyday use of the European Pressure Ulcer Advisory Panel system, its reliability has been evaluated in only a limited number of studies. Methods. A survey was carried out between September 2005 and February 2006 with a convenience sample of 1452 nurses from five European countries. Respondents classified 20 validated photographs as normal skin, blanchable erythema, pressure ulcers (four grades), moisture lesion or combined lesion. The nurses were familiar with the use of the European Pressure Ulcer Advisory Panel classification scale. Results. Pressure ulcers were often classified erroneously (kappa = 0.33) and only a minority of nurses reached a substantial level of agreement. Grade 3 lesions were regularly classified as grade 2. Non-blanchable erythema was frequently assessed incorrectly as blanchable erythema. Furthermore, the differential diagnosis between moisture lesions and pressure ulcers appeared to be complicated. Conclusion. Inter-observer reliability of the European Pressure Ulcer Advisory Panel classification system was low. Evaluation thus needs to focus on both the clarity and complexity of the system. Definitions and unambiguous descriptions of pressure ulcer grades and the distinction between moisture lesions will probably enhance clarity. To simplify the current classification system, a reduction in the number of grades is suggested.
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| 5. |
- Beeckman, D., et al.
(author)
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EPUAP classification system for pressure ulcers : European reliability study
- 2007
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In: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 60:6, s. 682-691
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Journal article (peer-reviewed)abstract
- AIM: This paper is a report of a study of the inter-observer reliability of the European Pressure Ulcer Advisory Panel pressure ulcer classification system and of the differential diagnosis between moisture lesions and pressure ulcers. BACKGROUND: Pressure ulcer classification is a valuable tool to provide a common description of ulcer severity for the purposes of clinical practice, audit and research. Despite everyday use of the European Pressure Ulcer Advisory Panel system, its reliability has been evaluated in only a limited number of studies. METHODS: A survey was carried out between September 2005 and February 2006 with a convenience sample of 1452 nurses from five European countries. Respondents classified 20 validated photographs as normal skin, blanchable erythema, pressure ulcers (four grades), moisture lesion or combined lesion. The nurses were familiar with the use of the European Pressure Ulcer Advisory Panel classification scale. RESULTS: Pressure ulcers were often classified erroneously (kappa = 0.33) and only a minority of nurses reached a substantial level of agreement. Grade 3 lesions were regularly classified as grade 2. Non-blanchable erythema was frequently assessed incorrectly as blanchable erythema. Furthermore, the differential diagnosis between moisture lesions and pressure ulcers appeared to be complicated. CONCLUSION: Inter-observer reliability of the European Pressure Ulcer Advisory Panel classification system was low. Evaluation thus needs to focus on both the clarity and complexity of the system. Definitions and unambiguous descriptions of pressure ulcer grades and the distinction between moisture lesions will probably enhance clarity. To simplify the current classification system, a reduction in the number of grades is suggested.
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| 6. |
- Brannvall, K, et al.
(author)
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19-Nortestosterone influences neural stem cell proliferation and neurogenesis in the rat brain
- 2005
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In: European Journal of Neuroscience. - Uppsala Univ, Ctr Biomed, Dept Neurosci, Neurobiol Unit, S-75123 Uppsala, Sweden. Karolinska Inst, Sect Expt Geriat, KFC Novum, S-14186 Huddinge, Sweden. Minerva Med Res Inst, FIN-00290 Helsinki, Finland. : WILEY. - 0953-816X .- 1460-9568. ; 21:4, s. 871-878
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Journal article (peer-reviewed)abstract
- Abuse of androgenic anabolic steroids can affect brain function leading to behavioural changes. In this study, the effects of the testosterone analogue, 19-nortestosterone, on rat neural stem cells was examined. The androgen receptor is expressed by cultured embryonic and adult neural stem cells, and is also present in the ventricular epithelium during development and in the adult brain in, among others, dentate gyrus. In neural stem cells stimulated with epidermal growth factor, nandrolone reduced cell proliferation, especially in adult ones. The decrease was abolished by flutamide, a receptor antagonist. Nandrolone also decreased the BrdU labelling of neural stem cells in the dentate gyrus, demonstrating an effect of the hormone on cell proliferation in vivo. The effect of nandrolone was observed with both female and male rats but it was more pronounced in pregnant rats, indicating an involvement of oestrogen in nandrolone action. Nandrolone also decreased the number of newly born neuronal cells in the dentate gyrus of male rats. The results show that nandrolone has important effects on the proliferation and differentiation of neural stem cells expressing the cognate androgen receptor. The data show that the use of nandrolone may severely affect the formation of neural stem cells and could therefore have long-term negative consequences in the brain.
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| 8. |
- de Simone, G., et al.
(author)
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Body build and risk of cardiovascular events in hypertension and left ventricular hypertrophy: the LIFE (Losartan Intervention For Endpoint reduction in hypertension) study
- 2005
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In: Circulation. - 1524-4539. ; 111:15, s. 1924-31
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Journal article (peer-reviewed)abstract
- BACKGROUND: Obesity may independently increase the risk of adverse events in hypertension with target-organ damage. We investigated whether body build was independently associated with higher cardiovascular risk and whether treatment with losartan relative to atenolol influenced the impact of body build on the primary composite end point of cardiovascular death, stroke, and myocardial infarction and on cardiovascular death in patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. METHODS AND RESULTS: The population of 9079 patients was divided as follows: thin (body mass index [BMI] <20 kg/m2, 2%), normal weight (BMI 20 to 24.9, 24%), overweight (BMI 25 to 29.9, 45%), and obese (class I: BMI 30 to 34.9, 21%; class II: BMI 35 to 39.9, 6%; class III: BMI > or =40, 2%). Incident diabetes increased progressively with BMI and was somewhat higher in the atenolol arm. Differences in gender and race were detected among the body build groups. Rates (Cox proportional hazard analysis) of the primary composite end point did not differ among body build groups after adjustment for age, gender, race, smoking habit, prevalent cardiovascular disease, and left ventricular hypertrophy. Cardiovascular death was more frequent among thin (P<0.05) and pooled class II-III obesity (both P<0.04) than normal-weight groups. Risk was not attenuated significantly by losartan treatment, nor did it interfere with the greater benefit of losartan- as opposed to atenolol-based treatment. CONCLUSIONS: In the LIFE study, stratification for classes of body build identified increased risk of cardiovascular mortality in both thin and moderately-to-severely obese individuals. This risk was not attenuated significantly by losartan treatment, nor did it interfere with the greater benefit of losartan-based treatment as opposed to atenolol-based treatment.
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| 9. |
- Devereux, R. B., et al.
(author)
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Blood pressure reduction and antihypertensive medication use in the losartan intervention for endpoint reduction in hypertension (LIFE) study in patients with hypertension and left ventricular hypertrophy
- 2007
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In: Curr Med Res Opin. - : Taylor & Francis. - 1473-4877 .- 0300-7995. ; 23:2, s. 259-70
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To compare blood pressure response and antihypertensive medication use visit-by-visit from baseline in patients receiving losartan-based or atenolol-based therapy in the LIFE study. RESEARCH DESIGN: LIFE was a randomized, double-blind trial comparing losartan-based and atenolol-based treatment regimens on the primary composite endpoint of death, myocardial infarction (MI), or stroke in 9193 patients aged 55-80 years with hypertension and left ventricular hypertrophy. Systolic and diastolic, pulse, and mean arterial pressures, blood pressure responder rates, distribution of open-label antihypertensive agents utilized, and the proportion of patients on randomized treatment were determined for each group at each clinic visit over a follow-up period of at least 4 years. RESULTS: Overall blood pressure reductions were comparable in the losartan-based and atenolol-based treatment groups. The mean reductions in sitting trough systolic and diastolic blood pressures from baseline to the end of follow-up (or last visit before a primary endpoint event) were 30.2/16.6 mmHg in the losartan group and 29.1/16.8 mmHg in the atenolol group. The time-averaged difference in overall mean arterial pressure was similar between groups. The proportion of patients on individual dose combinations varied visit by visit but was generally comparable between groups. During the entire study, 56% (2579/4605) of losartan-treated patients received at least one dose of the combination of losartan 100 mg plus hydrochlorothiazide 12.5 mg and 51% of atenolol-treated patients received 100 mg of atenolol plus hydrochlorothiazide 12.5 mg at some time during the study. CONCLUSIONS: Differences in blood pressure or distribution of add-on medications between treatment groups were not evident in the LIFE trial and, thus, cannot account for the observed outcome difference in the primary endpoint of risk reduction of the composite of cardiovascular death, stroke and MI favoring losartan.
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| 10. |
- Eijkelkamp, W. B., et al.
(author)
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Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: the RENAAL and LIFE studies
- 2007
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In: J Hypertens. - 0263-6352. ; 25:4, s. 871-6
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate whether a threshold exists for cardiovascular risk in type 2 diabetic patients with hypertension, the association between renal function and cardiovascular risk was examined across the entire physiological range of serum creatinine. DESIGN AND METHODS: The RENAAL and LIFE studies enrolled 1513 and 1195 patients with type 2 diabetes and hypertension, respectively. The relationship between baseline serum creatinine and the risk for a composite outcome of myocardial infarction, stroke or cardiovascular death was examined using Cox regression models. To adjust for heterogeneity between studies and treatment groups, these factors were included as strata when applicable. The analyses were conducted with adjustment for age, gender, smoking, alcohol use, blood pressure, heart rate, total and high-density lipoprotein (HDL) cholesterol, hemoglobin, albuminuria and prior cardiovascular disease. RESULTS: The hazard ratios across the baseline serum creatinine categories < 0.9 mg/dl, 0.9-1.2 mg/dl, 1.2-1.6 mg/dl, 1.6-2.8 mg/dl and >or= 2.8 mg/dl were 0.51 (95% confidence interval 0.34, 0.74), 0.74 (0.55, 1.00), 1.00 (reference), 1.24 (0.96, 1.59) and 1.67 (1.17, 2.91), respectively. Baseline serum creatinine (per mg/dl) strongly predicted the composite cardiovascular endpoint in LIFE [2.82(1.74,4.56), P < 0.001], RENAAL [1.41(1.12,1.79), P < 0.001], as well as the combined studies [1.51(1.21,1.87), P < 0.001]. CONCLUSION: A progressively higher risk for the composite cardiovascular endpoint was observed with incremental baseline serum creatinine in type 2 diabetic patients with hypertension, even within the normal range. Thus, there appears to be no serum creatinine threshold level for an increased cardiovascular risk. Baseline serum creatinine was a major independent risk factor for cardiovascular disease (www.ClinicalTrials.gov number NCT00308347).
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