| 1. |
- Alamidi, Daniel, et al.
(författare)
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T1 Relaxation Time in Lungs of Asymptomatic Smokers.
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Interest in using T1 as a potential MRI biomarker of chronic obstructive pulmonary disease (COPD) has recently increased. Since tobacco smoking is the major risk factor for development of COPD, the aim for this study was to examine whether tobacco smoking, pack-years (PY), influenced T1 of the lung parenchyma in asymptomatic current smokers.
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| 2. |
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| 3. |
- 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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| 4. |
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| 5. |
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| 6. |
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| 7. |
- 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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| 8. |
- Broberg, Marita, 1973, et al.
(författare)
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Cell swelling precedes seizures induced by inhibition of astrocytic metabolism.
- 2008
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Ingår i: Epilepsy Res.. - : Elsevier BV. - 0920-1211. ; 80:2-3, s. 132-41
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Tidskriftsartikel (refereegranskat)abstract
- It is currently unknown what processes take place at the interface between non-ictal and ictal activity during seizure initiation. In this study, using paralysed awake rats, we focally inhibited astrocytic metabolism with fluorocitrate (FC), causing seizures. We measured changes in electroencephalogram (EEG) (0-300 Hz), and extracellular ion-concentrations during ictal onsets defining possible relationships with impedance-determined cell swelling. In animals showing ictal activity (69%) there were spike-wave discharges, spike-wave discharges followed by spreading depression and spreading depression without any discharges. In a high proportion of spike-wave discharges (>95%), just prior to the first spike-wave discharge, there was a decrease in the volume of the extracellular space. Following the initiation of cell swelling and prior to discharges, there were increases in high-frequency (150-300 Hz) EEG activity, increases in extracellular potassium- and decreases in extracellular calcium-concentrations. We suggest that EEG and ionic changes are not causative of cell swelling. Cell swelling due to metabolic failure in astrocytes at the injected site may release excitatory amino acids. At the same time, our results suggest ion homeostasis is not maintained and increased neuronal excitability and synchronisation occur. These could be the drivers changing normal brain activity into ictal activity.
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| 9. |
- Broberg, Marita, 1973, et al.
(författare)
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Spreading depression: Evidence of five electroencephalogram phases.
- 2014
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Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 92:10, s. 1384-1394
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Tidskriftsartikel (refereegranskat)abstract
- Spreading depression (SD), a self-propagating wave of astroglial and neuronal depolarization, is an accompaniment of several neurological disorders including epilepsy. Its well-described features are initial depolarization, followed by EEG flattening. In this in vivo study in awake animals, the relationship of SDs to epileptiform activity was re-examined. We assessed SDs generated by mechanical stimulation and by metabolic inhibition with fluorocitrate. In addition to identifying prolonged EEG depression, we identified two periods, one prior to and another during depression, characterized by increases in power of specific frequencies that were sometimes associated with epileptiform discharges. The first period was characterized by ripple activity close to the induction site (88% of SDs with intracortical electrodes). The second period was characterized by localized low-frequency spikes (100% with dural screw electrodes, 65% with intracortical electrodes). By using fluorocitrate to induce SDs, the initial period was also characterized by runs of spikes (52%). Finally, with SDs induced by both methods, there was a period at the end of depression when additional, unprovoked SDs occurred (20%). Five stages of SD were defined by these phenomena, in the order: excitation, depression, excitation, depression, SD, with metabolic inhibition enhancing the expression of epileptiform spiking.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Elgqvist, Jörgen, 1963, et al.
(författare)
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Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab')2.
- 2006
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 66:4, s. 1228-37
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To elucidate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice. This study: (i) estimated the minimum required activity (MRA), giving a reasonable high therapeutic efficacy; and (ii) calculated the specific energy to tumor cell nuclei and the metastatic cure probability (MCP) using various assumptions regarding monoclonal-antibody (mAb) distribution in measured tumors. The study was performed using the alpha-particle emitter Astatine-211 (211At) labeled to the mAb MX35 F(ab')2. METHODS AND MATERIALS: Animals were inoculated intraperitoneally with approximately 1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq 211At-MX35 F(ab')2 (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq 211At-Rituximab F(ab')2 (n = 18). Eight weeks after treatment the animals were sacrificed and presence of macro- and microscopic tumors and ascites was determined. An MCP model was developed and compared with the experimentally determined tumor-free fraction (TFF). RESULTS: When treatment was given 4 weeks after cell inoculation, the TFFs were 25%, 22%, 50%, and 61% after treatment with 25, 50, 100, or 200 kBq (211)At-MX35 F(ab')2, respectively, the specific energy to irradiated cell nuclei varying between approximately 2 and approximately 400 Gy. CONCLUSION: As a significant increase in the therapeutic efficacy was observed between the activity levels of 50 and 100 kBq (TFF increase from 22% to 50%), the conclusion was that the MRA is approximately 100 kBq (211)At-MX35 F(ab')2. MCP was most consistent with the TFF when assuming a diffusion depth of 30 mum of the mAbs in the tumors.
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| 14. |
- Elgqvist, Jörgen, 1963, et al.
(författare)
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Alpha-radioimmunotherapy of intraperitoneally growing OVCAR-3 tumors of variable dimensions: Outcome related to measured tumor size and mean absorbed dose.
- 2006
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 47:8, s. 1342-50
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this work was to (a) investigate the efficacy of radioimmunotherapy using 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2 (nonspecific antibody) against differently advanced ovarian cancer in mice; (b) image the tumor growth on the peritoneum; and (c) calculate the specific energy and mean absorbed dose to tumors and critical organs. METHODS: Two experiments with 5-wk-old nude mice (n = 100 + 93), intraperitoneally inoculated with approximately 1 x 10(7) NIH:OVCAR-3 cells, were done. At either 1, 3, 4, 5, or 7 wk after inoculation animals were intraperitoneally treated with approximately 400 kBq 211At-MX35 F(ab')2 (n = 50 + 45), approximately 400 kBq 211At-Rituximab F(ab')2 (n = 25 + 24), or unlabeled Rituximab F(ab')2 (n = 25 + 24). At the time of treatment 29 animals were sacrificed and biopsies were taken for determination of tumor sizes using scanning electron microscopy (SEM). Eight weeks after each treatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. The specific energy and mean absorbed dose to tumors were calculated. The activity concentration was measured in critical organs and abdominal fluid. RESULTS: When given treatment 1, 3, 4, 5, or 7 wk after cell inoculation the tumor-free fraction (TFF) was 95%, 68%, 58%, 47%, 26%, and 100%, 80%, 20%, 20%, and 0% when treated with 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2, respectively. The SEM images revealed maximum tumor radius of approximately 30 mum 1 wk after cell inoculation, increasing to approximately 340 mum at 7 wk. Specific energy to cell nuclei varied between 0 and approximately 540 Gy, depending on assumptions regarding activity distribution and tumor size. The mean absorbed dose to thyroid, kidneys, and bone marrow was approximately 35, approximately 4, and approximately 0.3 Gy, respectively. CONCLUSION: Treatment with 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2 resulted in a TFF of 95%-100% when the tumor radius was < or =30 microm. The TFF was decreased (TFF < or = 20%) for 211At-Rituximab F(ab')2 when the tumor radius exceeded the range of the alpha-particles. The specific antibody gave for these tumor sizes a significantly better TFF, explained by a high mean absorbed dose (>22 Gy) from the activity bound to the tumor surface and probably some contribution from penetrating activity.
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| 15. |
- Elgqvist, Jörgen, 1963, et al.
(författare)
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Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with 211At-MX35 F(ab')2: therapeutic efficacy and myelotoxicity
- 2006
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Ingår i: Nucl Med Biol. - : Elsevier BV. - 0969-8051. ; 33:8, s. 1065-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate the therapeutic efficacy and myelotoxicity during fractionated radioimmunotherapy of ovarian cancer in mice. The study was performed using the monoclonal antibody MX35 F(ab')(2) labeled with the alpha-particle emitter (211)At. METHODS: Animals were intraperitoneally inoculated with approximately 1x10(7) cells of the cell line NIH:OVCAR-3. Four weeks later, the mice were given the first treatment. Six groups of animals were intraperitoneally injected with approximately 800, 3x approximately 267, approximately 400, 3x approximately 133, approximately 50 or 3x approximately 17 kBq (211)At-MX35 F(ab')(2) (n=18 in each group). The second and third injections for Groups 2, 4 and 6 were given 4 and 8 days after the first injection, respectively. As controls, animals were treated with unlabeled MX35 F(ab')(2) (n=12). Eight weeks after the last injection, the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. Blood counts were determined for each mouse in Groups 1 and 2 before the first injection and 3, 7, 11, 15 and 23 days after the first injection. The calculation of the mean absorbed dose to the bone marrow was based on the ratio between the (211)At-activity concentration in bone and blood [i.e., the bone-to-blood ratio (BBLR)] as well as that between the (211)At-activity concentration in bone marrow and blood [i.e., the bone-marrow-to-blood ratio (BMBLR)] and the cumulated activity and absorbed fraction of the alpha-particles emitted by (211)At in the bone marrow. RESULTS: The tumor-free fractions of animals were 56% and 41% when treated with approximately 800 kBq and 3x approximately 267 kBq (211)At-MX35 F(ab')(2), respectively; 39% and 28% when treated with approximately 400 kBq and 3x approximately 133 kBq (211)At-MX35 F(ab')(2), respectively; and 17% and 22% when treated with approximately 50 kBq or 3x approximately 17 kBq (211)At-MX35 F(ab')(2), respectively. The nadir of the white blood cell (WBC) counts was decreased (from 46% to 19%, compared with the baseline WBC counts) and delayed (from Day 4 to Day 11 after the first injection) during the fractionated treatment compared with the single-dose treatment. The percentage of injected activity per gram (%IA/g) for blood, bone and bone marrow all peaked 6 h after injection at 13.80+/-1.34%IA/g, 4.00+/-0.69%IA/g and 8.28+/-1.38%IA/g, respectively. The BBLR and BMBLR were 0.20+/-0.04 and 0.58+/-0.01, respectively. The mean absorbed dose to bone marrow was approximately 0.4 Gy after intraperitoneally injecting approximately 800 kBq (211)At-MX35 F(ab')(2). CONCLUSION: No advantage was observed in the therapeutic efficacy of using a fractionated regimen compared with a single administration, with the same total amount of administered activity. Alleviation of the myelotoxicity was observed during the fractionated regimen in terms of decreased suppression and delayed nadir of the WBC counts. No thrombocytopenia was observed during either regimen.
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| 16. |
- 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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| 17. |
- Engström, Katarina, 1956, et al.
(författare)
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The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells.
- 2006
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Ingår i: The American journal of pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 168:5, s. 1642-53
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid/round cell liposarcoma (MLS/RCLS) is the most common subtype of liposarcoma. Most MLS/RCLS carry a t(12;16) translocation, resulting in a FUS-DDIT3 fusion gene. We investigated the role of the FUS-DDIT3 fusion in the development of MLS/RCLS in FUS-DDIT3- and DDIT3-transfected human HT1080 sarcoma cells. Cells expressing FUS-DDIT3 and DDIT3 grew as liposarcomas in severe combined immunodeficient mice and exhibited a capillary network morphology that was similar to networks of MLS/RCLS. Microarray-based comparison of HT1080, the transfected cells, and an MLS/RCLS-derived cell line showed that the FUS-DDIT3- and DDIT3-transfected variants shifted toward an MLS/RCLS-like expression pattern. DDIT3-transfected cells responded in vitro to adipogenic factors by accumulation of fat and transformation to a lipoblast-like morphology. In conclusion, because the fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype when expressed in a primitive sarcoma cell line, MLS/RCLS may develop from cell types other than preadipocytes. This may explain the preferential occurrence of MLS/RCLS in nonadipose tissues. In addition, development of lipoblasts and the typical MLS/RCLS capillary network could be an effect of the DDIT3 transcription factor partner of the fusion oncogene.
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| 18. |
- 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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| 19. |
- Haag, Petra, et al.
(författare)
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Caspase-2 is a mediator of apoptotic signaling in response to gemtuzumab ozogamicin in acute myeloid leukemia
- 2022
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Ingår i: Cell Death Discovery. - : Springer Nature. - 2058-7716. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The antibody conjugate gemtuzumab ozogamicin (GO; Mylotarg((R))) provides targeted therapy of acute myeloid leukemia (AML), with recent approvals for patients with CD33-positive disease at diagnosis or relapse, as monotherapy or combined with chemotherapeutics. While its clinical efficacy is well documented, the molecular routes by which GO induces AML cell death warrant further analyses. We have earlier reported that this process is initiated via mitochondria-mediated caspase activation. Here we provide additional data, focusing on the involvement of caspase-2 in this mechanism. We show that this enzyme plays an important role in triggering apoptotic death of human AML cells after exposure to GO or its active moiety calicheamicin. Accordingly, the caspase-2 inhibitor z-VDVAD-fmk reduced GO-induced caspase-3 activation. This finding was validated with shRNA and siRNA targeting caspase-2, resulting in reduced caspase-3 activation and cleavage of poly [ADP-ribose] polymerase 1 (PARP-1). We previously demonstrated that GO-induced apoptosis included a conformational change of Bax into a pro-apoptotic state. Present data reveal that GO-treatment also induced Bid cleavage, which was partially reduced by caspase-2 specific inhibition while the effect on GO-induced Bax conformational change remained unaltered. In mononuclear cells isolated from AML patients that responded to GO treatment in vitro, processing of caspase-2 was evident, whereas in cells from an AML patient refractory to treatment no such processing was seen. When assessing diagnostic samples from 22 AML patients, who all entered complete remission (CR) following anthracycline-based induction therapy, and comparing patients with long versus those with short CR duration no significant differences in baseline caspase-2 or caspase-3 full-length protein expression levels were found. In summary, we demonstrate that GO triggers caspase-2 cleavage in human AML cells and that the subsequent apoptosis of these cells in part relies on caspase-2. These findings may have future clinical implications.
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| 20. |
- 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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| 21. |
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| 22. |
- Hedelin, Maria, 1964, et al.
(författare)
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Dietary phytoestrogens are not associated with risk of overall breast cancer but diets rich in coumestrol are inversely associated with risk of estrogen receptor and progesterone receptor negative breast tumors in Swedish women.
- 2008
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Ingår i: The Journal of nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 138:5, s. 938-945
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Tidskriftsartikel (refereegranskat)abstract
- Results from epidemiological and experimental studies indicate that phytoestrogens may protect against breast cancer. Because one of the biological effects of phytoestrogens is probably estrogenic, it's possible that the preventive effect on breast cancer differs by estrogen receptor (ER) or progesterone receptor (PR) status of the tumor. We evaluated the associations between dietary phytoestrogen (isoflavonoids, lignans, and coumestrol) intake and risk of breast cancer and whether the ER/PR statuses of the tumor influence this relationship. In 1991-2 a prospective population-based cohort study among Swedish pre- and postmenopausal women was performed, making questionnaire data available for 45,448 women. A total of 1014 invasive breast cancers were diagnosed until December 2004. Cox proportional hazards models were performed to estimate multivariate risk ratios, 95% CI for associations with risk of breast cancer. Intakes of lignan, isoflavonoid, or coumestrol were not associated with breast cancer risk overall or before or after 50 y of age. The effects of lignans or isoflavonoids were independent of receptor status. However, intake of coumestrol was associated with decreased risk of receptor negative tumors (ER-PR-) but not positive tumors. The risk of ER-PR- tumors was significantly lower (50%) in women with intermediate coumestrol intake compared with those who did not consume any. In conclusion, we found no association between intake of isoflavonoids or lignans and breast cancer risk. Our results of a decreased risk of ER-PR- tumors in women with intermediate intake of coumestrol could be due to chance because of the low intake. The results should be confirmed in other studies.
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| 23. |
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| 24. |
- 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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| 25. |
- Johansson, Ewa, 1964, et al.
(författare)
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Genotyping of Pseudomonas aeruginosa isolates from lung transplant recipients and aquatic environment-detected in-hospital transmission
- 2014
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Ingår i: Apmis. - : Wiley. - 0903-4641. ; 122:2, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Lung infection with Pseudomonas aeruginosa is common in lung transplant recipients and may lead to severe complications. Bacteriological surveillance aims to detect transmission of microbes between hospital environment and patients. We sought to determine whether genotyping of P. aeruginosa isolates could improve identifications of pathways of infection. From 2004 to 2009, we performed genotyping with multiple-locus variable number of tandem repeats analysis (MLVA) and pulsed-field gel electrophoresis (PFGE) of P. aeruginosa isolates cultured from lung transplant recipients at Sahlgrenska University Hospital, Gothenburg. During a small outbreak in 2008, cultivation and genotyping of isolates from sink and drains samples from the hospital ward were performed. Pseudomona aeruginosa from 11/18 patients were genotyped to unique strains. The remaining seven patients were carriers of a P. aeruginosa strain of cluster A genotype. Pseudomona aeruginosa was isolated in 4/8 water samples, typed by MLVA also as cluster A genotype and confirmed by PFGE to be similar or identical to the isolates from four transplanted patients. In conclusion, genotyping of isolates revealed a clonal relationship between patient and water isolates, indicating in-hospital transmission of P. aeruginosa. We suggest genotyping with MLVA for rapid routine surveillance, with the PFGE method used for extended, confirmatory analyses.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Johansson, Jan, et al.
(författare)
-
Qualified Vocational Education beyond 2000 - a report from a pilot project in Sweden
- 2000
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Ingår i: European Vocational Training Journal. - 0378-5068. ; :21, s. 7-15
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Tidskriftsartikel (refereegranskat)abstract
- A new form of qualified vocational education (QVE) was introduced as a pilot project in Sweden. QVE is a ew form of post-secondary education, long equested by industry. In QVE, onethird of instructional time is advanced pplication of theoretical knowledge at a workplace. This article reports on the evaluation of the pilot project and suggests that QVE has been successful. It goes on to discuss four options for continuing QVE in Sweden - but the choice belongs to the political process.
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| 33. |
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| 34. |
- Jönsson, Bodil, 1959, et al.
(författare)
-
Molecular epidemiology of Mycobacterium abscessus, with focus on cystic fibrosis.
- 2007
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Ingår i: Journal of clinical microbiology. - 0095-1137. ; 45:5, s. 1497-504
-
Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium abscessus has been isolated increasingly often from the respiratory tracts of cystic fibrosis (CF) patients. It is not known whether these organisms are transmitted from person to person or acquired from environmental sources. Here, colony morphology and pulsed-field gel electrophoresis (PFGE) pattern were examined for 71 isolates of M. abscessus derived from 14 CF patients, three non-CF patients with chronic respiratory M. abscessus infection or colonization, one patient with mastoiditis, and four patients with infected wounds, as well as for six isolates identified as environmental contaminants in various clinical specimens. Contaminants and wound isolates mainly exhibited smooth colony morphology, while a rough colony phenotype was significantly associated with chronic airway colonization (P=0.014). Rough strains may exhibit increased airway-colonizing capacity, the cause of which remains to be determined. Examination by PFGE of consecutive isolates from the same patient showed that they all represented a single strain, even in cases where both smooth and rough isolates were present. When PFGE patterns were compared, it was shown that 24 patients had unique strains, while four patients harbored strains indistinguishable by PFGE. Two of these were siblings with CF. The other two patients, one of whom had CF, had not had contact with each other or with the siblings. Our results show that most patients colonized by M. abscessus in the airways have unique strains, indicating that these strains derive from the environment and that patient-to-patient transmission rarely occurs.
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| 35. |
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| 36. |
- Kondori, Nahid, 1967, et al.
(författare)
-
Development of IgG antibodies to Exophiala dermatitidis is associated with inflammatory responses in patients with cystic fibrosis.
- 2014
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Ingår i: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. - : Elsevier BV. - 1873-5010. ; 13:4, s. 391-399
-
Tidskriftsartikel (refereegranskat)abstract
- The clinical importance of airway colonisation by the fungus Exophiala dermatitidis in patients with cystic fibrosis (CF) is unclear. We have previously shown that E. dermatitidis frequently colonises the airways of patients with CF. The aims of the present study were to determine whether patients who are colonised by E. dermatitidis have detectable fungal antigens in the circulation, develop anti-fungal antibodies, and show signs of inflammation and impaired respiratory function.
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| 37. |
- 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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| 38. |
- 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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| 39. |
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| 40. |
- Louka, A S, et al.
(författare)
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HLA in coeliac disease families: a novel test of risk modification by the 'other' haplotype when at least one DQA1*05-DQB1*02 haplotype is carried.
- 2002
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Ingår i: Tissue antigens. - 0001-2815 .- 1399-0039. ; 60:2, s. 147-54
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Tidskriftsartikel (refereegranskat)abstract
- Predisposition to coeliac disease (CD) involves HLA genes. We investigated whether any haplotypes modify risk when carried trans to a known high-risk haplotype, DQA1*05-DQB1*02. Earlier attempts to rank levels of risk contributed by the 'other' haplotype were burdened by use of case-control populations; haplotype frequencies were estimated and homozygosity was only presumed. In contrast, exact haplotypes can be determined and allele transmission can be traced in families. A similar study in narcolepsy reported strata of different degrees of predisposition, attributable to the 'other' haplotype. A gene dosage effect similar to that described for DQB1*02 in CD, has also been reported in narcolepsy. We genotyped 439 simplex/multiplex trios for DQA1 and DQB1. We designed a new statistic to test risk modulation by the trans haplotype, even if the affected offspring was homozygous. We tested for significant deviation in transmission of the 'other' haplotype, i.e., modification of DQA1*05-DQB1*02 risk. We also addressed the proposed difference in risk, between DQA1*05-DQB1*02 homozygotes and DQA1*05-DQB1*02/DQA1*0201-DQB1*02 heterozygotes, reported in Southern Europe. We confirmed a DQB1*02 gene dosage effect. However, no haplotypes were found to modify risk when carried trans to DQA1*05-DQB1*02, except DQA1*05-DQB1*02 and DQA1*0201-DQB1*02 which were already known. We did not find credible evidence for a difference in risk conferred by DQA1*05-DQB1*02 and DQA1*0201-DQB1*02, when carried with DQA1*05-DQB1*02. The new test, which directly inspects haplotype transmissions rather than estimated haplotype frequencies, was used to demonstrate that the 'other' haplotype (except DQA1*05-DQB1*02 and DQA1*0201-DQB1*02) does not modify risk conferred by DQA1*05-DQB1*02. The test is applicable to other diseases.
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| 41. |
- Næss, Sigrid, et al.
(författare)
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Refinement of the MHC risk map in a scandinavian primary sclerosing cholangitis population
- 2014
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
-
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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| 42. |
- 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
-
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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| 43. |
- Olsson, Marita
(författare)
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Building bridges between school and working life : a study of the approaches adopted by schools to create beneficial preconditions for young people’s entry into adult life and the working environment
- 2003
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Ingår i: European Vocational Training Journal. - 0378-5068. ; II:29, s. 71-80
-
Tidskriftsartikel (refereegranskat)abstract
- The labour market of today requires higher formal qualifications and broader knowledge, resulting in a greater risk of unemployment, especially among young people. For young people, unemployment can mean a threat to their personal values, such as the gaining of adult status. Schools are criticised for being detached from reality and for not being able to develop the knowledge and qualifications that working life demands. The purpose of this case study is to examine how schools with vocational training programmes organise their work in order, on the one hand, to impart the knowledge that modern working life demands and, on the other hand, to introduce young adolescents to adult life and the working environment.
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| 44. |
- Olsson, Marita, 1965, et al.
(författare)
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Contemporary Risk Estimates of Three HbA(1c) Variables for Myocardial Infarction in 101,799 Patients Following Diagnosis of Type 2 Diabetes
- 2015
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:8, s. 1481-1486
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE This study evaluated the risk of myocardial infarction (MI) by impaired glycemic control in a contemporary large cohort of patients with type 2 diabetes followed from diagnosis. Patients with type 2 diabetes diagnosed between 1995 and 2011 were retrieved from the Clinical Practice Research Datalink in the U.K., and followed from diagnosis until event of MI or end of study in 2013. Two subcohorts were defined: an early cohort with those diagnosed from 1997 to 2004 and a recent cohort with those diagnosed from 2004 to 2011. Association between each of three HbA(1c) metrics and MI was estimated using adjusted proportional hazards models. In the overall cohort (n = 101,799), the risk increase for MI per 1% (10 mmol/mol) increase in HbA(1c) was higher for updated latest and updated mean HbA(1c) of 1.11 (95% CI 1.09-1.13) and 1.15 (1.13-1.18) than for baseline HbA(1c) of 1.05 (1.03-1.06). In the early subcohort, the corresponding risk estimates were greater than those in the recent subcohort. When categorized, the updated latest variable showed an increased risk for HbA(1c) <6% (42 mmol/mol), relative category 6-7%, in the recent but not in the early subcohort, with hazard ratios of 1.23 (1.08-1.40) and 1.01 (0.84-1.22), respectively. The two time-updated HbA(1c) variables show a stronger relation with MI than baseline HbA(1c). The risk association between HbA(1c) and MI has decreased over time. In recently diagnosed patients with type 2 diabetes, an increased risk of MI exists at a current HbA(1c) of <6.0% (42 mmol/mol).
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| 45. |
- Olsson, Marita, 1965
(författare)
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EM Estimation in Phase Type Models
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of four articles whose theme in common is the class of phase type distributions. In the first article an EM algorithm is presented to estimate the parameters of a phase type distribution of fixed order. Also, it is shown that the algorithm can be used to approximate other continuous distributions by phase type distributions. In article number two, the EM algorithm is adjusted to handle fitting of phase type distributions to samples containing right censored and/or interval censored observations. The third article deals with approximations of standard errors of identifiable functions (e.g. the distribution function at a fixed point) of a fitted phase type distribution. Standard error approximations are calculated both by using asymptotic theory and by using the jackknife technique. The two methods are compared and evaluated by simulations in several examples. The last article presents a parametric model for estimation of the relapse time of a disease in certain clinical trials. The model is a special phase type model where the state space of the underlying Markov process is split into two parts; the first set of states represents the patient still being healthy, a transition to a second set of states takes place when the patient get a relapse, and a transition to an absorbing state represents the patient getting symptoms of the disease.
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| 46. |
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Olsson, Torsten, 1937, et al.
(författare)
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Cell Swelling, Seizures and Spreading Deprssion: An Impedance Study
- 2006
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522. ; 140:2
-
Tidskriftsartikel (refereegranskat)abstract
- The cellular processes that take place during the transition from pre-seizure state to seizure remain to be defined. In this study in awake, paralyzed rats, we used an electrical impedance measure of changes in extra-cellular intracranial volume to estimate changes in cell size in acute models of epilepsy. Animals were prepared with extradural electroencephalographic (EEG)/impedance electrodes and a venous catheter. On a subsequent day, animals were paralyzed, ventilated and treated with picrotoxin, kainic acid or fluorocitrate in doses that usually induce epileptiform discharges. We now report that increases in baseline impedance were induced by kainic acid and smaller increases by picrotoxin. We also demonstrated that epileptiform discharges were preceded by small, accelerated increases in impedance. Increases in baseline impedance were highly correlated with increases in power of non-ictal high frequency EEG activity. Seizures were accompanied by increases in impedance and all treatments induced transient, relatively large, increases in impedance often associated with unilateral reductions in low frequency EEG, likely periods of spreading depression. We conclude: cerebral cells swell in convulsant models of epilepsy, that there are pre-ictal accelerations in cell swelling, and that spreading depression-like events are frequently associated with seizures.
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