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- Shaw, L. M., et al.
(author)
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Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer's disease
- 2018
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 14:11, s. 1505-1521
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Journal article (peer-reviewed)abstract
- INTRODUCTION: The Alzheimer's Association convened a multidisciplinary workgroup to develop appropriate use criteria to guide the safe and optimal use of the lumbar puncture procedure and cerebrospinal fluid (CSF) testing for Alzheimer's disease pathology detection in the diagnostic process. METHODS: The workgroup, experienced in the ethical use of lumbar puncture and CSF analysis, developed key research questions to guide the systematic review of the evidence and developed clinical indications commonly encountered in clinical practice based on key patient groups in whom the use of lumbar puncture and CSF may be considered as part of the diagnostic process. Based on their expertise and interpretation of the evidence from systematic review, members rated each indication as appropriate or inappropriate. RESULTS: The workgroup finalized 14 indications, rating 6 appropriate and 8 inappropriate. DISCUSSION: In anticipation of the emergence of more reliable CSF analysis platforms, the manuscript offers important guidance to health-care practitioners and suggestions for implementation and future research. Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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- Fredholm, BB, et al.
(author)
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Consequences of eliminating adenosine A(1) receptors in mice
- 2003
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In: Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 1). - : Wiley. - 1098-2299 .- 0272-4391. ; 58, s. 350-
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Conference paper (peer-reviewed)abstract
- The second coding exon of the adenosine A, receptor gene was eliminated by homologous recombination. The phenotype of mice (mixed C57B6/129OlaHsd background) was studied, using siblings from matings of heterozygous mice. Among the offspring the ratio between+/+, +/-and -/-animals was 1:2:1. Over the first half-year-at least-growth and viability were the same in all genotypes. Binding of A(1) ligands was eliminated in-/-mice and halved in+/-mice. Blood pressure was increased in-/-mice and this was paralleled by an increase in plasma renin. Heart rate was unaffected, as was contractility. Furthermore, the response of the perfused heart to ischemia was similar in+/+and -/-hearts. However, remote preconditioning was eliminated in-/-mouse hearts. Tubuloglomerular feedback in the kidney was also lost in-/-mice. The analgesic response to a non-selective adenosing receptor agonist was lost in-/-mice, which also showed hyperalgesia in the tail-flick test. There was a slight hypoactivity in-/-mice, but responses to caffeine were essentially normal. The inhibition of excitatory neurotransmission in hippocampus by adenosine was lost in-/-mice and reduced in+/-mice. Responses to ATP were affected similarly. Hypoxic depression of synaptic transmission was essentially eliminated in hippocampus and hypoxic decrease in spinal respiratory neuron firing was markedly reduced. These results show that adenosine A, receptors play a physiologically important role in the kidney, spinal cord, and hippocampus and that they are critically important in the adaptive responses to hypoxia. (C) 2003 Wiley-Liss, Inc.
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- Hjaeresen, S., et al.
(author)
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MIF in the cerebrospinal fluid is decreased during relapsing-remitting while increased in secondary progressive multiple sclerosis
- 2022
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In: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X. ; 439
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Journal article (peer-reviewed)abstract
- Background: Macrophage migration inhibitory factor (MIF) is involved in the function of both the innate and adaptive immune systems and in neuroprotection and has recently been implicated in multiple sclerosis (MS). Objectives: Determination of MIF levels in the cerebrospinal fluid (CSF) of patients with distinct subtypes of MS and the cellular localization of MIF in human brain tissue. Methods: The levels of MIF were investigated in CSF from patients with clinically isolated syndrome (CIS) (n = 26), relapsing-remitting MS (RRMS) (n = 22), secondary progressive MS (SPMS) (n = 19), and healthy controls (HCs) (n = 24), using ELISA. The effect of disease-modifying therapies in the RRMS and SPMS cohorts were examined. Cellular distribution of MIF in the human brain was studied using immunochemistry and the newly available OligoInternode database. Results: MIF was significantly decreased in treatmentnaive CIS and RRMS patients compared to HCs but was elevated in SPMS. Interestingly, MIF levels were sex-dependent and significantly higher in women with CIS and RRMS. MIF expression in the human brain was localized to neurons, astrocytes, pericytes, and oligo5 oligodendrocytes but not in microglia. Conclusion: The finding that MIF was decreased in newly diagnosed CIS and RRMS patients but was high in patients with SPMS may suggest that MIF levels in CSF are regulated by local MIF receptor expression that affects the overall MIF signaling in the brain and may represent a protective mechanism that eventually fails.
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- Hjaeresen, S., et al.
(author)
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The levels of the serine protease HTRA1 in cerebrospinal fluid correlate with progression and disability in multiple sclerosis
- 2021
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In: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 268, s. 3316-3324
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Journal article (peer-reviewed)abstract
- Background High Temperature Requirement Serine Protease A1 (HTRA1) degrades extracellular matrix molecules (ECMs) and growth factors. It interacts with several proteins implicated in multiple sclerosis (MS), but has not previously been linked to the disease. Objective Investigate the levels of HTRA1 in cerebrospinal fluid (CSF) in different subtypes of MS and brain tissue. Methods Using ELISA, HTRA1 levels were compared in CSF from untreated patients with relapsing-remitting MS (RRMS, n = 23), secondary progressive MS (SPMS, n = 26) and healthy controls (HCs, n = 26). The effect of disease modifying therapies (DMTs) were examined in both patient groups. Cellular distribution in human brain was studied using immunochemistry and the oligointernode database, based on a single-nuclei RNA expression map. Results HTRA1 increased in RRMS and SPMS compared to HCs. DMT decreased HTRA1 levels in both types of MS. Using ROC analysis, HTRA1 cut-offs could discriminate HCs from RRMS patients with 100% specificity and 82.6% sensitivity. In the brain, HTRA1 was expressed in glia and neurons. Conclusion HTRA1 is a promising CSF biomarker for MS correlating with disease- and disability progression. Most cell species of the normal and diseased CNS express HTRA1 and the expression pattern could reflect pathological processes involved in MS pathogenesis.
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- Chandler, Jennifer A., et al.
(author)
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International Legal Approaches to Neurosurgery for Psychiatric Disorders
- 2021
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In: Frontiers in Human Neuroscience. - : Frontiers Media S.A.. - 1662-5161. ; 14
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Research review (peer-reviewed)abstract
- Neurosurgery for psychiatric disorders (NPD), also sometimes referred to as psychosurgery, is rapidly evolving, with new techniques and indications being investigated actively. Many within the field have suggested that some form of guidelines or regulations are needed to help ensure that a promising field develops safely. Multiple countries have enacted specific laws regulating NPD. This article reviews NPD-specific laws drawn from North and South America, Asia and Europe, in order to identify the typical form and contents of these laws and to set the groundwork for the design of an optimal regulation for the field. Key challenges for this design that are revealed by the review are how to define the scope of the law (what should be regulated), what types of regulations are required (eligibility criteria, approval procedures, data collection, and oversight mechanisms), and how to approach international harmonization given the potential migration of researchers and patients.
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