| 1. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 2. |
- Zannad, F., et al.
(författare)
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Clinical outcome endpoints in heart failure trials: a European Society of Cardiology Heart Failure Association consensus document
- 2013
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 15:10, s. 1082-1094
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Tidskriftsartikel (refereegranskat)abstract
- Endpoint selection is a critically important step in clinical trial design. It poses major challenges for investigators, regulators, and study sponsors, and it also has important clinical and practical implications for physicians and patients. Clinical outcomes of interest in heart failure trials include all-cause mortality, cause-specific mortality, relevant non-fatal morbidity (e.g. all-cause and cause-specific hospitalization), composites capturing both morbidity and mortality, safety, symptoms, functional capacity, and patient-reported outcomes. Each of these endpoints has strengths and weaknesses that create controversies regarding which is most appropriate in terms of clinical importance, sensitivity, reliability, and consistency. Not surprisingly, a lack of consensus exists within the scientific community regarding the optimal endpoint(s) for both acute and chronic heart failure trials. In an effort to address these issues, the Heart Failure Association of the European Society of Cardiology (HFA-ESC) convened a group of expert heart failure clinical investigators, biostatisticians, regulators, and pharmaceutical industry scientists (Nice, France, 12-13 February 2012) to evaluate the challenges of defining heart failure endpoints in clinical trials and to develop a consensus framework. This report summarizes the group's recommendations for achieving common views on heart failure endpoints in clinical trials.
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| 3. |
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| 4. |
- Unger, M. M., et al.
(författare)
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Unimpaired postprandial pancreatic polypeptide secretion in Parkinson's disease and REM sleep behavior disorder
- 2013
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:4, s. 529-533
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic polypeptide is released immediately after food ingestion. The release is operated by vagal-abdominal projections and has therefore been suggested as a test for vagal nerve integrity. Pathoanatomical and clinical studies indicate vagal dysfunction in early Parkinson's disease (PD). Methods: We assessed the postprandial secretion of pancreatic polypeptide and motilin in healthy controls (n = 18) and patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD, n = 10), a potential premotor stage of PD, as well as in drug-naive (n = 19) and treated (n = 19) PD patients. Results: The postprandial pancreatic polypeptide secretion showed a physiological pattern in all groups and even an enhanced response in drug-naive PD and iRBD. Motilin concentrations correlated with pancreatic polypeptide concentrations. Conclusions: Postprandial pancreatic polypeptide secretion is not a suitable test for vagal nerve integrity in PD. The unimpaired pancreatic polypeptide response in iRBD and PD might be explained by partially intact vagal-abdominal projections or compensatory mechanisms substituting a defective neuronal brain–gut axis.
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| 5. |
- Johansson, Viktoria, et al.
(författare)
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Microscopic Particles in Two Fractions of Fresh Cerebrospinal Fluid in Twins with Schizophrenia or Bipolar Disorder and in Healthy Controls
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Using scanning electron microscopy, microscopic structures have been identified in fresh cerebrospinal fluid (CSF) in patients with schizophrenia and bipolar disorder, but only rarely in control subjects. However, it has not been determined whether these microscopic particles represent state or trait markers, i.e. if their presence is related to clinical manifestations of the disease or if they also can be found in as yet asymptomatic individuals with a genetic liability. This question can be addressed by studying twins discordant or concordant for schizophrenia or bipolar disorder. Methodology/Principal Findings: We investigated microscopic structures in CSF in 102 individuals: 21 monozygotic and 16 dizygotic twins affected or not affected with schizophrenia, schizoaffective disorder or bipolar disorder and in 65 healthy singleton controls. A first and a second fraction of CSF was freshly applied on filters and examined by scanning electron microscopy technique. Spherical particles with lipid appearance averaging between 0.1 to 8.0 mu m in diameter were detected in the center of the filter as well as located in the margins of larger aggregates binding in a viscous state. Structures were found in 12 of 17 probands, 5 of 12 healthy co-twins and 3 of 73 healthy controls. Thus, a positive microscopic finding significantly increased the likelihood of belonging to the proband group (OR = 48, 95% CL: 8.2-550, p<0.0001) and the co-twin-group (OR = 16, 95% CL: 2.0-218, p = 0.006). Age, sex, history of alcohol abuse or anxiety syndrome, somatic disorder and markers of acute inflammatory activity did not account for group differences; nor did exposure to psychotropic medication. Conclusion: Presence of microscopic particles in CSF may possibly reflect trait dependent genetic or environmental vulnerability in patients with schizophrenia, schizoaffective disorder or bipolar disorder.
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| 6. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Blood-cerebrospinal fluid barrier dysfunction in patients with bipolar disorder in relation to antipsychotic treatment
- 2014
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 217:3, s. 143-146
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Tidskriftsartikel (refereegranskat)abstract
- Blood-cerebrospinal barrier (BCB) dysfunction has previously been shown in subjects with schizophrenia and depressed patients with attempted suicide. Bipolar disorder (BPD) shares clinical features with both these disorders, but it is unknown if the integrity of the BCB is altered also in BPD. To assess if BCB function in BPD we surveyed 134 mood-stabilized BPD patients and 86 healthy controls. Serum and cerebrospinal fluid (CSF) samples were collected and analyzed for albumin concentration by immunonephelometry. CSF/serum albumin ratio, an established measure of BCB function, was significantly elevated in BPD patients as compared to controls. After stratifying patients according to diagnostic subtype, BPD I patients had the highest CSF/serum albumin ratios. Moreover, BPD patients on antipsychotic treatment had higher CSF/serum albumin ratio than BPD patients on other treatments. When excluding BPD patients on antipsychotic treatment the difference in CSF/serum albumin ratio between the BPD and control groups disappeared. In conclusion, antipsychotic treatment in BPD is associated with elevated CSF/serum albumin ratio, tentatively as a sign of impaired BCB function. Whether this elevation is caused by antipsychotic treatment or is associated with a certain subtype of BPD, requiring antipsychotic treatment, remains to be determined. (C) 2014 Elsevier Ireland 'Ltd. All rights reserved.
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| 7. |
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| 8. |
- Liberg, B., et al.
(författare)
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Vertex-based morphometry in euthymic bipolar disorder implicates striatal regions involved in psychomotor function
- 2014
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Ingår i: Psychiatry Research-Neuroimaging. - : Elsevier BV. - 0925-4927 .- 1872-7123. ; 221:3, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that psychomotor disturbances in patients with bipolar disorder are associated with morphometric changes in functionally specific regions of the basal ganglia and thalamus. We used structural magnetic resonance imaging and vertex-based morphometry to investigate whether psychomotor performance is associated with changes in volume and shape in euthymic subjects with bipolar disorder (n=27) compared with matched healthy controls (n=27). We saw no significant differences between age- and sex-matched groups in motor performance. We found a statistically significant group difference in the shape of the right putamen in the absence of psychomotor disturbances. There was an association between shape and motor performance in controls that was lacking in patients. We conclude that euthymic subjects with bipolar disorder without psychomotor disturbances show shape changes in regions of the right putamen that contribute to executive functions and motor function. It may be that other brain regions sustain the psychomotor functions that produce nearly identical motor performance in both groups. (C) 2014 Elsevier Ireland Ltd. All rights reserved
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| 9. |
- Språngberg, A, et al.
(författare)
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SBU. Godartad prostataförstoring med avflödeshinder. En systematisk litteraturöversikt : Godartad prostataförstoring med avflödeshinder
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Slutsatser Godartad prostataförstoring (benign prostatahyperplasi, BPH) är ett vanligt tillstånd som med stigande ålder drabbar i princip alla män. En del av dessa män får urineringsproblem och cirka 4 500 opereras varje år för en förstorad prostata. Många med lindrigare besvär behandlas med läkemedel eller behöver ingen behandling alls. Avflödeshinder kan obehandlat ge allvarlig urinretention som skadar njurarna, och en urinstämma kan vara livshotande. För att avgränsa den grupp av män där problemen med urineringen beror på en förstorad prostata används ett tiotal olika diagnostiska metoder. När det gäller behandling finns det flera olika kirurgiska metoder, varav några är väl etablerade och andra av mer experimentell karaktär. Under 1990-talet har också flera läkemedel introducerats. SBU har därför bedömt att det funnits ett behov av att göra en systematisk genomgång av den vetenskapliga grunden för dessa olika metoder. Nedan följer de viktigaste slutsatserna av arbetet.
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| 10. |
- Axelsson, John, et al.
(författare)
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Effects of Sustained Sleep Restriction on Mitogen-Stimulated Cytokines, Chemokines and T Helper 1/T Helper 2 Balance in Humans
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. Methods: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00 - 07.00 h) followed by 5 days with restricted sleep (03.00 - 07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-alpha), interleukin (IL) -1 beta, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed. Results: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-alpha and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day. Conclusions: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences. BAS AK, 1991, IMMUNOLOGICAL REVIEWS, V123, P5
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