| 1. |
- Paul-Visse, Gesine, et al.
(författare)
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Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson's disease patients
- 2015
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 125:3, s. 1339-1346
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 mu g rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD.
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| 2. |
- Baldvinsdóttir, Bryndís, et al.
(författare)
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Adverse events during endovascular treatment of ruptured aneurysms : A prospective nationwide study on subarachnoid hemorrhage in Sweden
- 2023
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Ingår i: BRAIN AND SPINE. - : Elsevier. - 2772-5294. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A range of adverse events (AEs) may occur in patients with subarachnoid hemorrhage (SAH). Endovascular treatment is commonly used to prevent aneurysm re-rupture.Research question: The aim of this study was to identify AEs related to endovascular treatment, analyze risk factors for AEs and how AEs affect patient outcome.Material and methods: Patients with aneurysmal SAH admitted to all neurosurgical centers in Sweden during a 3.5-year period (2014-2018) were prospectively registered. AEs related to endovascular aneurysm treatment were thromboembolic events, aneurysm re-rupture, vessel dissection and puncture site hematoma. Potential risk factors for the AEs were analyzed using multivariate logistic regression. Functional outcome was assessed at one year using the extended Glasgow outcome scale.Results: In total, 1037 patients were treated for ruptured aneurysms. Of which, 715 patients were treated with endovascular occlusion. There were 115 AEs reported in 113 patients (16%). Thromboembolic events were noted in 78 patients (11%). Aneurysm re-rupture occurred in 28 (4%), vessel dissection in 4 (0.6%) and puncture site hematoma in 5 (0.7%). Blister type aneurysm, aneurysm smaller than 5 mm and endovascular techniques other than coiling were risk factors for treatment-related AEs. At follow-up, 230 (32%) of the patients had unfavorable outcome. Patients suffering intraprocedural aneurysm re-rupture were more likely to have unfavorable outcome (OR 6.9, 95% CI 2.3-20.9).Discussion and conclusion: Adverse events related to endovascular occlusion of a ruptured aneurysm were seen in 16% of patients. Aneurysm re-rupture during endovascular treatment was associated with increased risk of unfavorable functional outcome.
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| 3. |
- Díez-del-Molino, David, et al.
(författare)
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Population genomics reveals lack of greater white-fronted introgression into the Swedish lesser white-fronted goose
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Interspecific introgression is considered a potential threat to endangered taxa. One example where this has had a major impact on conservation policy is the lesser white-fronted goose (LWfG). After a dramatic decline in Sweden, captive breeding birds were released between 1981–1999 with the aim to reinforce the population. However, the detection of greater white-fronted goose (GWfG) mitochondrial DNA in the LWfG breeding stock led to the release program being dismantled, even though the presence of GWfG introgression in the actual wild Swedish LWfG population was never documented. To examine this, we sequenced the complete genomes of 21 LWfG birds from the Swedish, Russian and Norwegian populations, and compared these with genomes from other goose species, including the GWfG. We found no evidence of interspecific introgression into the wild Swedish LWfG population in either nuclear genomic or mitochondrial data. Moreover, Swedish LWfG birds are genetically distinct from the Russian and Norwegian populations and display comparatively low genomic diversity and high levels of inbreeding. Our findings highlight the utility of genomic approaches in providing scientific evidence that can help improve conservation management as well as policies for breeding and reinforcement programmes.
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| 4. |
- Holst, Anna, et al.
(författare)
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Cost-effectiveness analysis of internet-mediated cognitive behavioural therapy for depression in the primary care setting : results based on a controlled trial
- 2018
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective To perform a cost-effectiveness analysis of a randomised controlled trial of internet-mediated cognitive behavioural therapy (ICBT) compared with treatment as usual (Tall) for patients with mild to moderate depression in the Swedish primary care setting. In particular, the objective was to assess from a healthcare and societal perspective the incremental cost-effectiveness ratio (ICER) of ICBT versus TaU at 12 months follow-up. Design A cost-effectiveness analysis alongside a pragmatic effectiveness trial. Setting Sixteen primary care centres (PCCs) in south-west Sweden. Participants Ninety patients diagnosed with mild to moderate depression at the PCCs. Main outcome measure ICERs calculated as (Cost(ICBT)-Cost(TaU))/(Health outcome(ICBT)-Health outcome(TaU))=Delta Cost/Delta Health outcomes, the health outcomes being changes in the Beck Depression Inventory-II (BDI-II) score and quality-adjusted life-years (QALYs). Results The total cost per patient for ICBT was 4044 Swedish kronor (SEK) ((sic)426) (healthcare perspective) and SEK47679 ((sic)5028) (societal perspective). The total cost per patient for TaU was SEK4434 ((sic)468) and SEK50 343 ((sic)5308). In both groups, the largest cost was associated with productivity loss. The differences in cost per patient were not statistically significant. The mean reduction in BDI-ll score was 13.4 and 13.8 units in the ICBT and Tall groups, respectively. The mean QALYs per patient was 0.74 and 0.79 in the ICBT and TaU groups, respectively. The differences in BDI-11 score reduction and mean QALYs were not statistically significant. The uncertainty of the study estimates when assessed by bootstrapping indicated that no firm conclusion could be drawn as to whether ICBT treatment compared with Tall was the most cost-effective use of resources. Conclusions ICBT was regarded to be as cost-effective as TaU as costs, health outcomes and cost-effectiveness were similar for ICBT and TaU, both from a healthcare and societal perspective.
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| 5. |
- Hornborg, Sara, et al.
(författare)
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By-Catch Impacts in Fisheries: Utilizing the IUCN Red List Categories for Enhanced Product Level Assessment in Seafood LCAs
- 2013
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Ingår i: Environmental Management. - : Springer Science and Business Media LLC. - 0364-152X .- 1432-1009. ; 52:5, s. 1239-1248
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Tidskriftsartikel (refereegranskat)abstract
- Overexploitation of fish stocks causes concern not only to fisheries managers and conservation biologists, but also engages seafood consumers; more integrated product perspectives would be useful. This could be provided by life cycle assessment (LCA); however, further complements of present LCA methodology are needed to assess seafood production, one being by-catch impacts. We studied the scientific rationale behind using the IUCN Red List of Threatened Species (TM) for assessment of impacts relating to fish species' vulnerability. For this purpose, the current Red List status of marine fish in Sweden was compared to the advice given in fisheries as well as key life history traits known to indicate sensitivity to high fishing pressure. Further, we quantified the amount of threatened fish (vulnerable, endangered, or critically endangered) that was discarded in demersal trawl fisheries on the Swedish west coast. The results showed that not only did the national Red List of marine fish have a high consistency with advice given in fisheries and indices of vulnerability, the different fishing practices studied were also found to have vastly different amounts of threatened fish discarded per kilo landing. The suggested approach is therefore promising as a carrier of aggregated information on the extent to which seafood production interferes with conservation priorities, in particular for species lacking adequate stock assessment. To enable extensive product comparisons, it is important to increase coverage of fish species by the global IUCN Red List, and to reconsider the appropriate assessment unit (species or stocks) in order to avoid false alarms.
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| 6. |
- Mattsson, Per, et al.
(författare)
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Nimodipine-induced improved survival rate of facial motor neurons following intracranial transection of the facial nerve in the adult rat
- 1999
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Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 90:4, s. 760-765
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Tidskriftsartikel (refereegranskat)abstract
- OBJECT: Neuronal survival is an important factor in the achievement of functional restitution after peripheral nerve injuries. Intracranial tumors or trauma may cause patients to exhibit a temporary or permanent facial nerve palsy. Nimodipine, which acts as an antagonist to L-type voltage-gated calcium channels, has been shown to be neuroprotective in various lesion models of the central and peripheral nervous systems. The aim of the present study was to evaluate the effect of nimodipine on motor neuron survival in the facial motor nucleus following intracranial transection of the adult rat facial nerve. METHODS: The facial nerve was cut intracranially in the posterior cranial fossa. Nimodipine was administered orally preoperatively for 3 days and postoperatively for up to 1 month, after which the number of neuronal profiles was quantified. The glial reaction was studied in the facial nucleus for up to 1 month by using immunocytochemical analysis. There was a significantly larger proportion of surviving motor neurons 1 month postinjury in animals treated with nimodipine (61+/-6.7%) in comparison with untreated animals (26.8+/-11.3%). Immunocytochemical analysis showed an increase in the amount of OX42 (microglia), ED1 (macrophages), and anti-glial fibrillary acidic protein (astrocytes) ipsilateral to the nerve injury; however, there was no difference between the two experimental groups of animals 2 to 28 days after surgery. CONCLUSIONS: The authors propose a neuroprotective role for nimodipine, which may be useful as a "cranial nerve protective agent" following insults such as head injury or skull base surgery.
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| 7. |
- Mattsson, Per, et al.
(författare)
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Nimodipine promotes regeneration and functional recovery after intracranial facial nerve crush
- 2001
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 347:1, s. 106-117
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Tidskriftsartikel (refereegranskat)abstract
- The calcium flow inhibitor, nimodipine, has been shown to promote motor neuron survival in the facial nucleus after intracranial facial nerve transection. However, it has not been known whether the neuroprotective effects primarily involve survival of nerve cell bodies or outgrowth and/or myelination of nerve fibers. Here, we studied the effects of nimodipine in a different injury model in which the facial nerve was unilaterally crushed intracranially. This lesion caused complete anterograde degeneration and partial retrograde degeneration that were studied with a combination of several stereological methods. Nimodipine did not attenuate the modest lesion-induced neuronal loss (13%) but accelerated the time course of functional recovery and axonal regrowth, inducing increased numbers and sizes of myelinated axons in the facial nerve. It is interesting to note that nimodipine also enlarged the axons and the myelin sheaths in the nonlesioned facial nerve, which points to the possibility of using this substance for new clinical applications to promote axonal growth and remyelination.
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| 8. |
- Mattsson, Per, et al.
(författare)
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The novel pyrrolopyrimidine PNU-101033-E improves facial motor neuron survival following intracranial axotomy of the facial nerve in the adult rat
- 1999
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 16:9, s. 793-803
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal survival is important to functional restitution following axotomy. Proximal lesions of the facial nerve, due to head trauma or tumor growth, for example, may cause long-standing or even permanent facial nerve palsy. Betamethasone has been used by several neurosurgical clinics for the treatment of postoperative facial nerve palsy; however, this practice is based only on clinical experience. The aim of the present study was to explore the putative effect on facial motor neuron survival of a novel lazaroid (pyrrolopyrimidine, PNU-101033-E) and furthermore to compare the effects with those of betamethasone, following intracranial transection of the facial nerve in adult rats. Both agents are known to inhibit lipid peroxidation by free radical scavenging. The lesion model used has recently been reported to induce massive neuronal cell death with a relative survival of 26.8 +/- 11.3% 1 month after lesion. Oral administration of lazaroids or daily injections of betamethasone followed surgery for 1 month, after which quantification of motor neuronal profiles was performed in the facial nucleus. Lazaroid-treated animals showed a significantly enhanced neuronal survival (68.0 +/- 9.8%), whereas no significant difference was found in betamethasone-treated animals (33.1 +/- 11.7%). The microglial and astrocytic responses in the facial nucleus were intense on the operated sides in betamethasone-treated as well as lazaroid-treated animals, and no differences in comparison with untreated animals were found. In conclusion, we found that the novel pyrrolopyrimidine PNU-101033-E, but not betamethasone, significantly enhanced nerve cell survival. This agent may therefore serve as a useful neuroprotective agent following intracranial trauma to the facial nerve and should be further evaluated for clinical use.
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| 9. |
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| 10. |
- Nordblom, Jonathan, et al.
(författare)
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FGF1 containing biodegradable device with peripheral nerve grafts induces corticospinal tract regeneration and motor evoked potentials after spinal cord resection
- 2012
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 30:2, s. 91-102
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Repairing the spinal cord with peripheral nerve grafts (PNG) and adjuvant acidic fibroblast growth factor (FGF1) has previously resulted in partial functional recovery. To aid microsurgical placement of PNGs, a graft holder device was previously developed by our group. In hope for a translational development we now investigate a new biodegradable graft holder device containing PNGs with or without FGF1.Methods: Rats were subjected to a T11 spinal cord resection with subsequent repair using twelve white-to-grey matter oriented PNGs prepositioned in a biodegradable device with or without slow release of FGF1. Animals were evaluated with BBB-score, electrophysiology and immunohistochemistry including anterograde BDA tracing.Results: Motor evoked potentials (MEP) in the lower limb reappeared at 20 weeks after grafting. MEP responses were further improved in the group treated with adjuvant FGF1. Reappearance of MEPs was paralleled by NF-positive fibers and anterogradely traced corticospinal fibers distal to the injury. BBB-scores improved in repaired animals.Conclusions: The results continue to support that the combination of PNGs and FGF1 may be a regeneration strategy to reinnervate the caudal spinal cord. The new device induced robust MEPs augmented by FGF1, and may be considered for translational research.
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