| 1. |
- Berg, Tove, et al.
(författare)
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Gene expression analysis of membrane transporters and drug-metabolizing enzymes in the lung of healthy and COPD subjects.
- 2014
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Ingår i: Pharmacology research & perspectives. - : Wiley. - 2052-1707. ; 2:4, s. e00054-
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Tidskriftsartikel (refereegranskat)abstract
- This study describes for the first time the expression levels of genes encoding membrane transporters and drug-metabolizing enzymes in the lungs of ex-smoking patients with chronic obstructive pulmonary disease (COPD). Membrane transporters and drug-metabolizing enzymes are key determinants of drug uptake, metabolism, and elimination for systemically administered as well as inhaled drugs, with consequent influence on clinical efficacy and patient safety. In this study, while no difference in gene expression was found between healthy and COPD subjects, we identified a significant regional difference in mRNA expression of both membrane transporters and drug-metabolizing enzymes between central and peripheral tissue in both healthy and COPD subjects. The majority of the differentially expressed genes were higher expressed in the central airways such as the transporters SLC2A1 (GLUT1), SLC28A3 (CNT3), and SLC22A4 (OCTN1) and the drug-metabolizing enzymes GSTZ1, GSTO2, and CYP2F1. Together, this increased knowledge of local pharmacokinetics in diseased and normal lung may improve modeling of clinical outcomes of new chemical entities intended for inhalation therapy delivered to COPD patients. In addition, based on the similarities between COPD and healthy subjects regarding gene expression of membrane transporters and drug-metabolizing enzymes, our results suggest that clinical pharmacological studies in healthy volunteers could be a valid model of COPD patients regarding drug disposition of inhaled drugs in terms of drug metabolism and drug transporters.
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| 2. |
- Bohman, Hannes, 1965-, et al.
(författare)
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Thicker carotid intima layer, thinner media layer and higher intima/media ratio in women with recurrent depressive disorders : a pilot study using non-invasive high frequency ultrasound
- 2010
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Ingår i: World Journal of Biological Psychiatry. - : Informa Healthcare. - 1562-2975 .- 1814-1412. ; 11:1, s. 71-75
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Tidskriftsartikel (refereegranskat)abstract
- Background. Growing evidence indicates that depression is an important risk factor for coronary heart disease. Thus, the aim of the present study has been to investigate if young women with adolescent onset and recurrent depressive disorders have signs of carotid intima and media changes already at the age of 30. Methods. Fifteen subjects with adolescent onset recurrent depressive disorders, mean age 31.5 years, were compared to 20 healthy women with a mean age of 39.6 years. The thickness of carotid artery intima and media was assessed, using non-invasive high-frequency ultrasound (25MHz). Results. The subjects with recurrent depressive disorders had significantly thicker carotid intima, significantly thinner carotid media and significantly higher intima/media ratio despite the fact that they were about 10 years younger than the healthy women. Hypertension, obesity or smoking could not explain the results. Conclusion. Already at the age of 30, subjects with recurrent depressive disorders with adolescent onset do have early signs of carotid intima and media changes, indicating a less healthy artery wall, despite otherwise no clinical signs of cardiovascular disease.
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| 3. |
- Elgqvist, Jörgen, 1963, et al.
(författare)
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Intraperitoneal Alpha-Radioimmunotherapy of Advanced Ovarian Cancer in Nude Mice using Different High Specific Activities
- 2010
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Ingår i: World Journal of Oncology. - : Elmer Press, Inc.. - 1920-4531. ; 1:3, s. 101-110
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to investigate the therapeutic efficacy of advanced ovarian cancer in mice, using α-radioimmunotherapy with different high specific activities. The study was performed using the monoclonal antibody (mAb) MX35 F(ab´)2 labeled with the α-particle emitter 211At.Methods: Animals were intraperitoneally inoculated with ≥1 × 107 cells of the ovarian cancer cell line NIH:OVCAR-3. Four weeks later 9 groups of animals were given 25, 50, or 400 kBq 211At-MX35 F(ab´)2 with specific activities equal to 1/80, 1/500, or 1/1200 (211At atom/number of mAbs) for every activity level respectively (n = 10 in each group). As controls, animals were given PBS or unlabeled MX35 F(ab´)2 in PBS (n = 10 in each group). Eight weeks after treatment the animals were sacrificed and the presence of macroscopic tumors was determined by meticulous ocular examination of the abdominal cavity. Cumulated activity and absorbed dose calculations on tumor cells and tumors were performed using in house developed program. Specimens for scanning electron-microscopy analysis were collected from the peritoneum at the time of dissection.Results: Summing over the different activity levels (25, 50, and 400 kBq 211At-MX35 F(ab´)2) the number of animals with macroscopic tumors was 13, 17, and 22 (n = 30 for each group) for the specific activities equal to 1/80, 1/500, or 1/1200, respectively. Logistic-regression analysis showed a significant trend that higher specific activity means less probability for macroscopic tumors (P = 0.02).Conclusions: Increasing the specific activity indicates a way to enhance the therapeutic outcome of advanced ovarian cancer, regarding macroscopic tumors. Further studies of the role of the specific activity are therefore justified.
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| 4. |
- Glogner, S., et al.
(författare)
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The association between BMI and hospitalization for heart failure in 83 021 persons with Type 2 diabetes: a population-based study from the Swedish National Diabetes Registry
- 2014
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 31:5, s. 586-594
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Tidskriftsartikel (refereegranskat)abstract
- AIM'S: The aim was to To study the relationship between BMI and hospitalization for heart failure in people with Type 2 diabetes. METHODS: We identified 83 021 individuals with Type 2 diabetes from the Swedish National Diabetes Registry during 1998-2003, who were followed until hospitalization for heart failure, death or end of follow-up on 31 December 2009. Cox regression analyses were performed, adjusting for age, sex, HbA1c , blood pressure, diabetes duration, smoking, microalbuminuria, cardiac co-morbidities, glucose-lowering and anti-hypertensive medications. RESULTS: During a median follow-up of 7.2 years, 10 969 patients (13.2%) were hospitalized with heart failure. By categories of BMI, with BMI 20 to < 25 kg/m2 as the reference, hazard ratios for patients during follow-up were 1.07 (95% CI 0.91-1.26) for a mean BMI of < 20 kg/m2 , 1.04 (95% CI 0.98-1.11) for BMI 25 to < 27.5 kg/m2 , 1.22 (95% CI 1.15-1.30) for BMI 27.5 to < 30 kg/m2 , 1.54 (95% CI 1.45-1.63) for BMI 30 to < 35 kg/m2 , 2.16 (95% CI 2.00-2.33) for BMI 35 to < 40 kg/m2 and 3.22 (95% CI 2.88-3.60) for BMI 40 kg/m2 or higher. There was a significant interaction between BMI and sex (P = 0.0006), with numerically higher hazard ratios for hospitalization for heart failure within each BMI category for men than for women. CONCLUSIONS: Obesity is strongly related to hospitalization for heart failure in people with Type 2 diabetes, and the relationship is somewhat stronger for men than for women. Preventing weight gain and promoting weight loss may be crucial in reducing the incidence of future hospitalizations for heart failure in this population.
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| 5. |
- Hedelin, M., et al.
(författare)
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Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33 000 women from the general population
- 2010
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Ingår i: BMC Psychiatry. - 1471-244X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low intake of fish, polyunsaturated fatty acids (PUFA) and vitamin D deficiency has been suggested to play a role in the development of schizophrenia. Our aim was to evaluate the association between the intake of different fish species, PUFA and vitamin D and the prevalence of psychotic-like symptoms in a population-based study among Swedish women. Methods: Dietary intake was estimated using a food frequency questionnaire among 33 623 women aged 30-49 years at enrolment (1991/92). Information on psychotic- like symptoms was derived from a follow-up questionnaire in the years 2002/03. Participants were classified into three predefined levels: low, middle and high frequency of symptoms. The association between diet and psychotic- like symptoms was summarized in terms of relative risks (RR) and corresponding 95% confidence intervals and was evaluated by energy-adjusted multinomial logistic regression. Results: 18 411 women were classified as having a low level of psychotic- like symptoms, 14 395 as middle and 817 as having a high level. The risk of high level symptoms was 53% (95% CI, 30-69%) lower among women who ate fish 3-4 times per week compared to women who never ate fish. The risk was also lower for women with a high intake of omega-3 and omega-6 PUFA compared to women with a lower intake of these fatty acids. The effect was most pronounced for omega-6 PUFAs. The RR comparing the highest to the lowest quartile of omega-6 PUFAs intake was 0.78 (95% CI, 0.64-0.97). The associations were J-shaped with the strongest reduced risk for an intermediate intake of fish or PUFA. For fatty fish (herring/mackerel, salmon-type fish), the strongest inverse association was found for an intermediate intake (RR: 0.81, 95% CI, 0.66-0.98), whereas a high intake of fatty fish was associated with an increased risk of psychotic- like symptoms (RR: 1.90, 95% CI, 1.34-2.70). Women in the highest compared with the lowest quartile of vitamin D consumption experienced a 37% (95% CI, 22-50%) lower risk of psychotic- like symptoms. Conclusion: Our findings raise a possibility that adult women with a high intake of fish, omega-3 or omega-6 PUFA and vitamin D have a lower rate of psychotic- like symptoms.
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| 6. |
- Hov, J. R., et al.
(författare)
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Electrostatic Modifications of the Human Leukocyte Antigen-DR P9 Peptide-Binding Pocket and Susceptibility to Primary Sclerosing Cholangitis
- 2011
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 53:6, s. 1967-1976
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Tidskriftsartikel (refereegranskat)abstract
- The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 x 10(-32) and P = 1.8 x 10(-22) in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. Conclusion: The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DR beta chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (HEPATOLOGY 2011;53:1967-1976)
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| 7. |
- Lind, Marcus, 1976, et al.
(författare)
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Glycaemic control and incidence of heart failure in 20 985 patients with type 1 diabetes: an observational study
- 2011
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736 .- 1474-547X. ; 378:9786, s. 140-146
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Tidskriftsartikel (refereegranskat)abstract
- Background Poor glycaemic control is associated with microvascular and macrovascular complications in type 1 diabetes, but whether glycaemic control is associated with heart failure in such patients is not known. We aimed to assess this association in a large cohort of patients with type 1 diabetes identified from the Swedish national diabetes registry. Methods We identified all patients (aged >= 18 years) with type 1 diabetes and no known heart failure who were registered in the national diabetes registry between January, 1998, and December, 2003. These patients were followed up until hospital admission for heart failure, death, or end of follow-up on Dec 31, 2009. We calculated incidence categorised by glycated haemoglobin A(1c) (HbA(1c)) values, and we assessed the association between patients' characteristics, including HbA(1c), and heart failure. Findings In a cohort of 20 985 patients with mean age of 38.6 years (SD 13.3) at baseline, 635 patients (3%) were admitted to hospital with a primary or secondary diagnosis of heart failure during a median follow-up of 9.0 years (IQR 7.3-11.0), with an incidence of 3.38 events per 1000 patient-years (95% CI 3.12-3.65). Incidence increased monotonically with HbA(1c), with a range of 1.42-5.20 per 1000 patient-years between patients in the lowest (<6.5%) and highest (>= 10.5%) categories of HbA(1c). In a Cox regression analysis, with adjustment for age, sex, duration of diabetes, cardiovascular risk factors, and baseline or intervening acute myocardial infarction and other comorbidities, the hazard ratio for development of heart failure was 3.98 (95% CI 2.23-7.14) in patients with HbA(1c) of 10.5% or higher compared with a reference group of patients with HbA(1c) of less than 6.5%. Risk of heart failure increased with age and duration of diabetes. Other modifiable factors associated with increased risk of heart failure were smoking, high systolic blood pressure, and raised body-mass index. In a subgroup of 18 281 patients (87%) with data for blood lipids, higher HDL cholesterol was associated with lower risk of heart failure, but there was no association with LDL cholesterol. Interpretation The positive association between HbA(1c) and risk of heart failure in fairly young patients with type 1 diabetes indicates a potential for prevention of heart failure with improved glycaemic control.
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| 8. |
- Lind, Marcus, 1976, et al.
(författare)
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The relationship between glycaemic control and heart failure in 83,021 patients with type 2 diabetes
- 2012
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 55:11, s. 2946-2953
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine the relationship between glycaemic control and hospitalisation for heart failure in patients with type 2 diabetes. Patients included in the Swedish National Diabetes Register (NDR) during 1998-2003 were followed until hospitalisation for heart failure, death or 31 December 2009. Unadjusted and adjusted incidence rates for heart failure were estimated by Poisson regression and relative risk was estimated by Cox regression. In 83,021 patients with type 2 diabetes, 10,969 (13.2%) were hospitalised with a primary or secondary diagnosis of heart failure during a mean follow-up of 7.2 years. The incidence increased by male sex (p < 0.001), older age (p < 0.001) and longer diabetes duration (p < 0.001). In Cox regression adjusting for risk factors of heart failure the HR per each percentage unit higher HbA(1c) (10 mmol/mol) for heart-failure hospitalisation was 1.12 (95% CI 1.10, 1.14). By category of HbA(1c) the HR for heart failure hospitalisation was: HbA(1c) 6.0 to < 7.0% (42 to < 53 mmol/mol), 0.91 (95% CI 0.84, 0.98); HbA(1c) 7.0 to < 8.0% (53 to < 64 mmol/mol), 0.99 (95% CI 0.91, 1.07); HbA(1c) 8.0 to < 9.0% (64 to < 75 mmol/mol), 1.10 (95% CI 1.01, 1.20); HbA(1c) 9.0 to < 10.0% (75 to < 86 mmol/mol), 1.27 (95% CI 1.15, 1.41); HbA(1c) a parts per thousand yen10.0 % (a parts per thousand yen86 mmol/mol), 1.71 (1.51, 1.93) (reference HbA(1c) < 6% [42 mmol/mol]). The HR for patients with HbA(1c) 7.0 to < 8.0% (53 to < 64 mmol/mol) compared with patients with HbA(1c) 6.0 to < 7.0% (42 to < 53 mmol/mol) was 1.09 (95% CI 1.03, 1.14). Poor glycaemic control (HbA(1c) > 7% [53 mmol/mol]) is associated with an increased risk of hospitalisation for heart failure in patients with type 2 diabetes.
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| 9. |
- Næss, Sigrid, et al.
(författare)
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Refinement of the MHC risk map in a scandinavian primary sclerosing cholangitis population
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within the major histocompatibility complex (MHC) represent the strongest genetic susceptibility factors for primary sclerosing cholangitis (PSC). Identifying the causal variants within this genetic complex represents a major challenge due to strong linkage disequilibrium and an overall high physical density of candidate variants. We aimed to refine the MHC association in a geographically restricted PSC patient panel.
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| 10. |
- Olaya-Contreras, Patricia, 1964, et al.
(författare)
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THE INFLUENCE OF DISTRESS ON DISABILITY, PHYSICAL ACTIVITY AND PAIN INTENSITY AFTER 7 DAYS OF ACUTE SEVERE LOW BACK PAIN
- 2011
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X. ; 65:8
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain (LBP) is described as highly recurrent and frequently persistent public health worldwide. The “stay active” concept has been regarded as the most appropriate treatment recommendation for patients with acute LBP. The objective of this study was to evaluate the influence of distress on disability, physical activity and pain intensity in subjects with severe acute LBP. Methods A Randomised Control Trial (RCT) was conducted, 99 employed subjects (mean age 45 years, 20–63), 61% white- and 39% blue-collar workers with acute LBP were examined within 48 h after the onset of pain. All patients were initially assessed using the Depression Anxiety and Positive Outlook Scale (DAPOS) and the Tampa Scale of Kinesiophobia (TSK) questionnaires. Thereafter, the patients documented the following in a diary over a 7-day period: pain intensity, disability rating index (DRI) and step count (pedometer). Linear Mixed Models (LMM) for repeated measures were employed for the statistical analyses. All results were adjusted for age, gender, treatment, number of days and for the interaction term (treatment *DAPOS-D). Results Prospectively, DRI and pain intensity responses were differentially mediated by the treatment, in interaction with the scores of DAPOS (p<0.05). Patients with high scores on DAPOS exhibited higher risk for worse pain-disability after follow-up. Additionally, patients with higher baseline scores on TSK (>38) had a lower step count over time (p<0.05). Conclusion Depressed mood and fear of movement affect the outcomes of disability, the level of physical activity and the pain intensity in patients with acute LBP.
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