| 1. |
- Eriksdotter-Jönhagen, Maria, et al.
(author)
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Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease.
- 2012
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 33:1, s. 18-28
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Journal article (peer-reviewed)abstract
- Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer's disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability.
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| 2. |
- Ferreira, Daniel, et al.
(author)
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Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor
- 2015
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 43, s. 1059-1072
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Journal article (peer-reviewed)abstract
- © 2015-IOS Press and the authors. New therapies with disease-modifying effects are urgently needed for treating Alzheimer's disease (AD). Nerve growth factor (NGF) protein has demonstrated regenerative and neuroprotective effects on basal forebrain cholinergic neurons in animal studies. In addition, AD patients treated with NGF have previously shown improved cognition, EEG activity, nicotinic binding, and glucose metabolism. However, no study to date has analyzed brain atrophy in patients treated with NGF producing cells. In this study we present MRI results of the first clinical trial in patients with AD using encapsulated NGF biodelivery to the basal forebrain. Six AD patients received the treatment during twelve months. Patients were grouped as responders and non-responders according to their twelve-months change in MMSE. Normative values were created from 131 AD patients from ADNI, selecting 36 age-and MMSE-matched patients for interpreting the longitudinal changes in MMSE and brain atrophy. Results at baseline indicated that responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) Aβ1-42. However, they showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments. At follow-up, responders showed less brain shrinkage and better progression in the clinical variables and CSF biomarkers. Noteworthy, two responders showed less brain shrinkage than the normative ADNI group. These results together with previous evidence supports the idea that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD with both symptomatic and disease-modifying effects.
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| 3. |
- Karami, Azadeh, et al.
(author)
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Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease
- 2015
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:11, s. 1316-1328
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Journal article (peer-reviewed)abstract
- Introduction: The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF). The purpose of this study was to see if EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT, and acetylcholinesterase. Method: Encapsulated cell implants releasing NGF (EC-NGF) were surgically implanted bilaterally in the basal forebrain of six AD patients for 12 months and cholinergic markers in CSF were analyzed. Results: Activities of both enzymes were altered after 12 months. In particular, the activity of soluble ChAT showed high correlation with cognition, CSF tau and amyloid-beta, in vivo cerebral glucose utilization and nicotinic binding sites, and morphometric and volumetric magnetic resonance imaging measures. Discussion: A clear pattern of association is demonstrated showing a proof-of-principle effect on CSF cholinergic markers, suggestive of a beneficial EC-NGF implant therapy.
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| 6. |
- Dahl, S., et al.
(author)
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High prevalence of pituitary hormone deficiency in both unilateral and bilateral optic nerve hypoplasia
- 2019
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 108:9, s. 1677-1685
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Journal article (peer-reviewed)abstract
- Aim This study examined the prevalence of neurological impairment and pituitary hormone deficiency (PHD) in patients with unilateral and bilateral optic nerve hypoplasia (ONH). Methods A population-based cross-sectional cohort study of 65 patients (51% female) with ONH was conducted in Stockholm. Of these were 35 bilateral and 30 unilateral. The patients were below 20 years of age, living in Stockholm in December 2009 and found through database searching. The median age at the analysis of the results in January 2018 was 16.1 years (range 8.1-27.5 years). Neurological assessments and blood sampling were conducted, neuroradiology was reviewed and growth curves were analysed. Diagnoses of PHDs were based on clinical and biochemical evidence of hormone deficiency. Results Neurological impairments were identified in 47% of the patients and impairments in gross and fine motor function were more prevalent in bilateral ONH (p < 0.001). In addition, 9% had cerebral palsy and 14% had epilepsy. The prevalence of PHD was 29 and 19% had multiple PHD. Conclusion Children with ONH had a high risk of neurological impairment, especially in bilateral disease. Both unilateral and bilateral ONH signified an increased prevalence of PHD and all these children should be endocrinologically followed up until completed puberty.
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| 7. |
- Liberg, Benny, et al.
(author)
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Motor imagery in bipolar depression with slowed movement.
- 2013
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In: The Journal of nervous and mental disease. - 1539-736X. ; 201:10, s. 885-93
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Journal article (peer-reviewed)abstract
- We hypothesized that motor retardation in bipolar depression is mediated by disruption of the pre-executive stages of motor production. We used functional magnetic resonance imaging to investigate neural activity during motor imagery and motor execution to elucidate whether brain regions that mediate planning, preparation, and control of movement are activated differently in subjects with bipolar depression (n = 9) compared with healthy controls (n = 12). We found significant between-group differences. During motor imagery, the patients activated the posterior medial parietal cortex, the posterior cingulate cortex, the premotor cortex, the prefrontal cortex, and the frontal poles more than the controls did. Activation in the brain areas involved in motor selection, planning, and preparation was altered. In addition, limbic and prefrontal regions associated with self-reference and the default mode network were altered during motor imagery in bipolar depression with motor retardation.
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| 8. |
- Pettersson, Karin, 1972, et al.
(author)
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Metoder och verktyg för utvärdering av kursinslag i informationskompetens
- 2014
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Reports (other academic/artistic)abstract
- Syftet har varit att skapa en verktygslåda med förslag på metoder och verktyg att använda vid utvärdering av kursinslag inom området informationskompetens, av relevans för högskole- och gymnasiebibliotek. Projektet har haft tre faser. I den första gjordes en litteraturgenomgång av internationell forskningslitteratur kring utvärdering. Litteraturstudien mynnade ut i en sammanställning av metoder och verktyg för utvärdering av kursinslag i informationskompetens. I fas två testades ett urval av de sammanställda utvärderingsverktygen på biblioteken i Göteborg, Lund och Mölnlycke. Resultaten från testerna integrerades med sammanställningen från litteraturstudien till det som är projektets huvudresultat, verktygslådan. Projektets tredje fas är spridning av resultaten i form av verktygslådan.
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| 9. |
- Selin, Lotta, et al.
(author)
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High-dose versus low-dose of oxytocin for labour augmentation : a randomised controlled trial
- 2019
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In: Women and Birth. - : ELSEVIER. - 1871-5192 .- 1878-1799. ; 32:4, s. 356-363
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Journal article (peer-reviewed)abstract
- Problem: Delayed labour progress is common in nulliparous women, often leading to caesarean section despite augmentation of labour with synthetic oxytocin.Background: High-or low-dose oxytocin can be used for augmentation of delayed labour, but evidence for promoting high-dose is weak.Aim: To ascertain the effect on caesarean section rate of high-dose versus low-dose oxytocin for augmentation of delayed labour in nulliparous women.Methods: Multicentre parallel double-blind randomised controlled trial (ClinicalTrials.gov: NCT01587625) in six labour wards in Sweden. Healthy nulliparous women at term with singleton cephalic fetal presentation, spontaneous labour onset, confirmed delay in labour and ruptured membranes (n = 1351) were randomised to labour augmentation with either high-dose (6.6 mU/minute) or low-dose (3.3 mU/minute) oxytocin infusion.Findings: 1295 women were included in intention-to-treat analysis (high-dose n = 647; low-dose n = 648). Caesarean section rates did not differ between groups (12.4% and 12.3%, 95% Confidence Interval -3.7 to 3.8). Women with high-dose oxytocin had: shorter labours (-23.4 min); more uterine tachysystole (43.2% versus 33.5%); similar rates of instrumental vaginal births, with more due to fetal distress (43.8% versus 22.7%) and fewer due to failure to progress (39.6% versus 58.8%). There were no differences in neonatal outcomes.Discussion: Our study could not confirm results of two systematic reviews indicating, with weak evidence, that use of high-dose oxytocin was associated with lower frequency of caesarean section.Conclusion: We found no advantages for routine use of high-dose oxytocin in the management of delay in labour. Low-dose oxytocin regimen is recommended to avoid unnecessary events of tachysystole and fetal distress.
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| 10. |
- Shams, Mana, et al.
(author)
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Cerebrospinal Fluid Metals and the Association with Cerebral Small Vessel Disease.
- 2020
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In: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 78:3, s. 1229-1236
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Journal article (peer-reviewed)abstract
- Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma.Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels.This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-β (Aβ) 42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models.No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aβ42, T-tau, P-tau, and CSF/serum albumin ratios (p < 0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOEɛ4 carriers.CSF iron levels are elevated with cerebral microbleeds in APOEɛ4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients.
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