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- Burman, Pia, et al.
(författare)
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Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality
- 2013
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:4, s. 1466-1475
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Tidskriftsartikel (refereegranskat)abstract
- Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for Objective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism Design and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with Main Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for Results: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence Conclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response
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| 2. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 5. |
- Borga, Magnus, et al.
(författare)
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Improvement in Magnetic Resonance Imaging Relating to Correction of Chemical Shift Artifact and Intensity Inhomogeneity
- 2011
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Patent (populärvet., debatt m.m.)abstract
- Present invention discloses systems and methods for improvement of magnetic resonance images. Correction of a chemical shift artefact in an image acquired from a magnetic resonance imaging system is obtained by a system and a method involving iterative - compensation for the misregistration effect in an image domain. Correction of an intensity inhomogeneity in such images is obtained by a system and a method involving locating voxels corresponding to pure adipose tissue and estimating correction field from these points.
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| 6. |
- Calner, Mikael, et al.
(författare)
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d(13)C chemostratigraphy in the Lower-Middle Ordovician succession of Oland (Sweden) and the global significance of the MDICE
- 2014
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Ingår i: GFF. - : Informa UK Limited. - 2000-0863 .- 1103-5897. ; 136:1, s. 48-54
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Tidskriftsartikel (refereegranskat)abstract
- Based on the Tingskullen drillcore, we present the first continuous carbon isotope stratigraphy from the Lower-Middle Ordovician orthoceratite limestone of oland, Sweden. The extremely condensed Tremadocian and Floian stages include large gaps as well as the Ceratopyge Regressive Event and the widespread Evae transgression accompanied by prominent shifts in the C-13 record. The Dapingian and Darriwilian stages are characterised by low sedimentation rates and a relatively complete sedimentary record. A total of 99 whole-rock samples were analysed for carbon isotope geochemistry from the Ordovician part of the succession (46m thick). The most striking anomaly detected is the middle Darriwilian isotope carbon excursion (MDICE) that appears unusually well developed and complete for the region, and thus forms an important proxy for intercontinental correlation of the succession.
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| 8. |
- Dahlqvist Leinhard, Olof, 1978-, et al.
(författare)
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Quantifying differences in hepatic uptake of the liver specific contrast agents Gd-EOB-DTPA and Gd-BOPTA : a pilot study
- 2012
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Ingår i: European Radiology. - : Springer Berlin/Heidelberg. - 0938-7994 .- 1432-1084. ; 22:3, s. 642-653
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To develop and evaluate a procedure for quantifying the hepatocyte-specific uptake of Gd-BOPTA and Gd-EOB-DTPA using dynamic contrast-enhanced (DCE) MRI. Methods Ten healthy volunteers were prospectively recruited and 21 patients with suspected hepatobiliary disease were retrospectively evaluated. All subjects were examined with DCE-MRI using 0.025 mmol/kg of Gd-EOB-DTPA. The healthy volunteers underwent an additional examination using 0.05 mmol/kg of Gd-BOPTA. The signal intensities (SI) of liver and spleen parenchyma were obtained from unenhanced and enhanced acquisitions. Using pharmacokinetic models of the liver and spleen, and an SI rescaling procedure, a hepatic uptake rate, K Hep, estimate was derived. The K Hep values for Gd-EOB-DTPA were then studied in relation to those for Gd-BOPTA and to a clinical classification of the patient’s hepatobiliary dysfunction. Results K Hep estimated using Gd-EOB-DTPA showed a significant Pearson correlation with K Hep estimated using Gd-BOPTA (r = 0.64; P < 0.05) in healthy subjects. Patients with impaired hepatobiliary function had significantly lower K Hep than patients with normal hepatobiliary function (K Hep = 0.09 ± 0.05 min-1 versus K Hep = 0.24 ± 0.10 min−1; P < 0.01). Conclusions A new procedure for quantifying the hepatocyte-specific uptake of T 1-enhancing contrast agent was demonstrated and used to show that impaired hepatobiliary function severely influences the hepatic uptake of Gd-EOB-DTPA. Key Points • The liver uptake of contrast agents may be measured with standard clinical MRI. • Calculation of liver contrast agent uptake is improved by considering splenic uptake. • Liver function affects the uptake of the liver-specific contrast agent Gd-EOB-DTPA. • Hepatic uptake of two contrast agents (Gd-EOB-DTPA, Gd-BOPTA) is correlated in healthy individuals. • This method can be useful for determining liver function, e.g. before hepatic surgery
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| 9. |
- Dahlqvist Leinhard, Olof
(författare)
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Quantitative Magnetic Resonance in Diffuse Neurological and Liver Disease
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Magnetic resonance (MR) imaging is one of the most important diagnostic tools in modern medicine. Compared to other imaging modalities, it provides superior soft tissue contrast of all parts of the body and it is considered to be safe for patients. Today almost all MR is performed in a nonquantitative manner, only comparing neighboring tissue in the search for pathology. It is possible to quantify MR-signals and relate them to their physical entities, but time consuming and complicated calibration procedures have prevented this being used in a practical manner for clinical routines. The aim of this work is to develop and improve quantification methods in MRspectroscopy (MRS) and MR-imaging (MRI). The techniques are intended to be applied to diffuse diseases, where conventional imaging methods are unable to perform accurate staging or to reveal metabolic changes associated with disease development.Methods: Proton (1H) MRS was used to characterize the white matter in the brain of multiple sclerosis (MS) patients. Phosphorus (31P) MRS was used to evaluate the energy metabolism in patients with diffuse liver disease. A new quantitative MRI (qMRI) method was invented for accurate, rapid and simultaneous quantification of B1, T1, T2, and proton density. A method for automatic assessment of visceral adipose tissue volume based on an in- and out-ofphase imaging protocol was developed. Finally, a method for quantification of the hepatobiliary uptake of liver specific T1 enhancing contrast agents was demonstrated on healthy subjects.Results: The 1H MRS investigations of white matter in MS-patients revealed a significant correlation between tissue concentrations of Glutamate and Creatine on the one hand and the disease progression rate on the other, as measured using the MSSS. High accuracy, both in vitro and in vivo, of the measured MR-parameters from the qMRI method was observed. 31P MRS showed lower concentrations of phosphodiesters, and a higher metabolic charge in patients with cirrhosis, compared to patients with mild fibrosis and to controls. The adipose tissue quantification method agreed with estimates obtained using manual segmentation, and enabled measurements which were insensitive to partial volume effects. The hepatobiliary uptake of Gd-EOB-DTPA and Gd-BOPTA was significantly correlated in healthy subjects.Conclusion: In this work, new methods for accurate quantification of MR parameters in diffuse diseases in the liver and the brain were demonstrated. Several applications were shown where quantitative MR improves the interpretation of observed signal changes in MRI and MRS in relation to underlying differences in physiology and pathophysiology.
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