| 1. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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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. |
- Erlinge, D., et al.
(författare)
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Bivalirudin versus Heparin Monotherapy in Myocardial Infarction
- 2017
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:12, s. 1132-1142
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Tidskriftsartikel (refereegranskat)abstract
- Background The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. Methods In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. Results A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). Conclusions Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).
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| 4. |
- Lindvall, O, et al.
(författare)
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Cell therapy and transplantation in Parkinson's disease
- 2001
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : De Gruyter. - 1434-6621 .- 1437-4331. ; 39:4, s. 356-361
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Tidskriftsartikel (refereegranskat)abstract
- Transplanted human fetal dopamine neurons can reinnervate the striatum in patients with Parkinson's disease (PD). Recent findings using positron emission tomography indicate that the grafts are functionally integrated and restore dopamine release in the patient's striatum. The grafts can exhibit long-term survival without immunological rejection and despite an ongoing disease process and continuous antiparkinsonian drug treatment. In the most successful cases, patients have been able to withdraw L-dopa treatment after transplantation and resume an independent life. About two-thirds of grafted patients have shown clinically useful, partial recovery of motor function. The major obstacle for the further development of this cell replacement strategy is that large amounts of human fetal mesencephalic tissue are needed for therapeutic effects. Stem cells hold promise as a virtually unlimited source of self-renewing progenitors for transplantation. The possibility to generate dopamine neurons from such cells is now being explored using different approaches. However, so far the generated neurons have survived poorly after transplantation in animals.
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| 5. |
- Marklund, Peter, et al.
(författare)
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Extensive inflammatory cell infiltration in human skeletal muscle in response to an ultra-endurance exercise bout in experienced athletes.
- 2013
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 114:1, s. 66-72
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Tidskriftsartikel (refereegranskat)abstract
- The impact of a 24h ultra-endurance exercise bout on systemic and local muscle inflammatory reactions was investigated in nine experienced athletes. Blood and muscle biopsies were collected before (PRE), immediately after the exercise (POST) and after 28h of recovery (POST28). Circulating blood levels of leukocytes, CK, CRP and selected inflammatory cytokines were assessed together with the evaluation of the occurrence of inflammatory cells (CD3(+), CD8(+), CD68(+)) and the expression of major histocompatibility complex class-I (MHC class-I) in skeletal muscle. An extensive inflammatory cell infiltration occurred in all athletes and the number of CD3(+), CD8(+) and CD 68(+) cells were 2-3 fold higher at POST28 compared to PRE (P<0.05). The inflammatory cell infiltration was associated with a significant increase in the expression of MHC class-I in muscle fibers. There was a significant increase in blood leukocyte count, IL-6, IL-8, CRP and CK at POST. At POST28 total leukocytes, IL-6 and CK had declined, whereas IL-8 and CRP continued to increase. Increases in IL-1β and TNF-α were not significant. There were no significant associations between the magnitude of the systemic and local muscle inflammatory reactions. Signs of muscle degenerative and regenerative events were observed in all athletes with various degrees of severity and were not affected by the ultra-endurance exercise bout. In conclusion, a low-intensity but very prolonged single endurance exercise bout can generate a strong inflammatory cell infiltration in skeletal muscle of well-trained experienced ultra-endurance athletes, and the amplitude of the local reaction is not proportional to the systemic inflammatory response.
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| 6. |
- Aineskog, Helena, et al.
(författare)
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Serum S100B correlates with health-related quality of life and functional outcome in patients at 1 year after aneurysmal subarachnoid haemorrhage
- 2022
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Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 164:8, s. 2209-2218
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early, objective prognostication after aneurysmal subarachnoid haemorrhage (aSAH) is difficult. A biochemical marker would be desirable. Correlation has been found between levels of the protein S100 beta (S100B) and outcome after aSAH. Timing and clinical usefulness are under investigation.METHODS: Eighty-nine patients admitted within 48 h of aSAH were included. Modified ranking scale (mRS), EuroQoL health-related quality of life measure (EQ-5Dindex) and EuroQoL visual analogue scale (EQ-VAS) values were evaluated after 1 year. S100B was measured in blood samples collected at admission and up to day 10.RESULTS: S100B correlated significantly with EQ-5Dindex and mRS, but not EQ-VAS at 1 year after aSAH. A receiver operating characteristic analysis for peak S100B values (area under the curve 0.898, 95% confidence interval 0.828-0.968, p < 0.0001), with a cutoff of 0.4 μg/l, yielded 95.3% specificity and 68% sensitivity for predicting unfavourable outcome. Dichotomized S100B (> 0.4 μg/l vs ≤ 0.4 μg/l), age and Hunt and Hess grading scale score (HH) were associated with unfavourable mRS outcome in univariate logistic regression analysis. Dichotomized S100B was the only variable independently correlated with unfavourable mRS outcome in a multivariate logistic regression analysis.CONCLUSIONS: For the first time, S100B was shown to correlate with mRS and health-related quality of life at 1 year after aSAH. Peak S100B can be used as a prognostic factor for unfavourable outcome measured as dichotomized mRS after aSAH. A peak value cutoff of 0.4 μg/l is suggested. Ethical approval no: 2013/366-31, 4th of February 2014.
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| 7. |
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| 8. |
- Appelros, Peter, et al.
(författare)
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Comorbidity in Stroke-Survivors : Prevalence and Associations with Functional Outcomes and Health
- 2021
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier. - 1052-3057 .- 1532-8511. ; 30:10
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The purpose of this study was to evaluate the prevalence and impact of stroke-related comorbidity in a community-based sample of stroke survivors. We sought to find out which types of comorbidity that were most important with respect to the patients' functional outcomes and general health.MATERIALS AND METHODS: All stroke survivors (n = 330) living in a medium-sized Swedish municipality were included. Patient records were reviewed to determine the presence of comorbidities. A selection of patient reported outcomes were used to assess subjective symptoms, functional outcomes, and general health. Logistic regression models were used to investigate the association between comorbidities, residual symptoms, and subjective symptoms on the one hand, and functional outcomes and general health on the other hand.RESULTS: Hypertension (80%) was the most common cardiovascular risk factor. Ischemic heart disease was found in 18% and congestive heart failure in 10%. Of non-cardiovascular disorders, orthopaedic diseases were commonest (30%). Psychiatric disorders and cognitive impairment were present in 11% and 12% respectively. Hemiparesis is associated with both functional outcomes and general health. Additionally, orthopedic disorders, vertigo, cognitive impairment, nicotine use, chronic pulmonary disorders, and age, are associated with different functional outcomes. Psychiatric, orthopedic and neurological disorders are related to general health. The patient-reported outcome measure "feeling of tiredness" is important for many of the outcomes, while "feeling depressed" and "having pain" are associated with general health.CONCLUSIONS: Many medical conditions, several of which have received little attention so far, are associated with functional outcome and general health in stroke survivors. If the intention is to describe comorbidity relevant to function and general health in stroke patients, disorders that hitherto have received little attention, must be considered.
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| 9. |
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| 10. |
- Appelros, Peter, et al.
(författare)
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Comorbidity in stroke survivors in a medium-sized Swedish municipality
- 2023
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Ingår i: Brain Injury. - : Informa Healthcare. - 0269-9052 .- 1362-301X. ; 37:Suppl. 1, s. 135-136
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: The purpose of this study was to evaluate the prevalence and impact of stroke-related comorbidity in a community-based sample of stroke survivors. With respect to the patients’ functional outcomes and general health, we wanted to find out which types of comorbidity were most important.Materials and Methods: All stroke survivors (n = 330) living in a medium-sized Swedish municipality were included. To determine the presence of comorbidities patient records were reviewed. A selection of patient reported outcomes were used to assess subjective symptoms, functional outcomes, and general health. All patients were asked to answer a questionnaire, the Swedish Stroke Register (Riksstroke). Three questions from the questionnaire were used as additional measures of comorbidity. “Do you feel tired?,” “Do you have pain?” and “Do you feel depressed?” As outcome measures the patient reported measures from the Riksstroke questionnaire were used: * Do you still have problems after your stroke? * Have you been able to return to the life and activities you had before the stroke? * How is your mobility now? * Do you get help from someone when visiting the toilet? * Do you get help with dressing and undressing? * How do you assess your general health? Logistic regression models were used to investigate the association between comorbidities, residual symptoms, and subjective symptoms on the one hand, and functional outcomes and general health on the other hand.Results: Hypertension (80%) was the most common cardiovascular risk factor. Ischemic heart disease was found in 18% and congestive heart failure in 10%. Of non-cardiovascular disorders, orthopedic diseases were commonest (30%). Psychiatric disorders and cognitive impairment were present in 11% and 12% respectively. Logistic regression analyses found that hemiparesis was associated with both poorer functional outcomes and lower general health. Additionally, orthopedic disorders, vertigo, cognitive impairment, nicotine use, chronic pulmonary disorders, and older age, were also associated with poorer functional outcomes. Psychiatric, orthopedic and neurological disorders were associated with poorer general health. The patient-reported outcome measure “feeling of tiredness” was a predictor of both outcomes, while “feeling depressed” and “having pain” were associated with poorer general health.Conclusions: Many medical conditions, several of which have received little attention so far, are associated with poorer functional outcome and lower general health among stroke survivors. Future research into comorbidities relevant to function and general health in stroke patients could further focus on these disorders that hitherto have received little attention.
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| 11. |
- Appelros, Peter, et al.
(författare)
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Stroke prevalence in a medium-sized Swedish municipality
- 2021
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Ingår i: Acta Neurologica Scandinavica. - : Munksgaard Forlag. - 0001-6314 .- 1600-0404. ; 143:2, s. 210-216
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Many patients who have had stroke survive with functional disability for years. Stroke prevalence is a fundamental measure of the impact of stroke in society. Stroke prevalence has never been evaluated in Sweden.MATERIALS & METHODS: 2019 with respect to stroke survivors (ICD-10 I60-I69) living in Kumla (population 21,738), a municipality well representative of Sweden.RESULTS: 330 individuals with stroke were found, of which 42% were women. The mean age was 74.1 years in men and 75.1 years in women. 11.5% of the patients had more than one stroke. The mean duration since the first stroke was 8.3 years. The crude prevalence per 100,000 was 1754 in men, 1281 in women and 1518 in both sexes. Adjusted to the European population, the ratio was 1570 per 100,000, and to the World population 936 per 100,000.CONCLUSIONS: In spite of a declining stroke incidence in Sweden, the stroke prevalence in Kumla, Sweden, is relatively high. Comparisons with other studies indicate that a decline in prevalence may have occurred since the early 2000s. Modern registers can support data collection, but the index stroke may have occurred almost forty years back in time.
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| 12. |
- Arvidsson Lindvall, Mialinn, 1977-, et al.
(författare)
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Experiences of living with balance limitations after first-ever stroke
- 2023
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Konferensbidrag (refereegranskat)abstract
- Background: Stroke is the leading cause of serious, long-term disability among adults. Balance control after stroke may be affected due to motor impairment such as muscle weakness, spasticity and impaired sensory function and also cognitive deficits may affect balance control. The balance limitations affect walking and independence in activities of daily living. Having good balance has been described as an important factor in outdoor walking and for participation in exercises. Studies in which persons with stroke describe their experience of balance in everyday life are scarce.Purpose: The aim of the present presentation is to describe experiences of living with balance limitations in everyday life after first-ever stroke.Methods: Twenty persons initially agreed to participate; however, one person later declined further participation, thus giving a sample size of 19 participants (10 females and 9 men), aged between 42-92 years. The inclusion criteria were: having had a first-ever stroke and having self-reported impaired balance, unaffected speech, independence in toileting and dressing, and walking ability indoors and outdoors with or without a walking aid. A qualitative data collection through individual interviews was conducted. Data was analysed by means of an inductive content analysis covering both the manifest and the latent content of the transcribed interviews.Results: The participants' experiences of balance and its influence in everyday life, are presented in two themes. The first theme “Feeling dizzy and unstable is a continuous challenge”, revolves around participants' descriptions of balance as a constant feeling of dizziness and unsteadiness. The second theme “Feeling trust and confidence despite dizziness and unsteadiness” is about perceived abilities and feelings of confidence about still being able to do things oneself, despite the dizziness and unsteadiness.Conclusion(s): All participants experienced the balance limitations as a continuous challenge in everyday life, yet they also felt trust and confidence and experienced that they still managed their everyday life. In future research it would be of interest to establish which strategies can make persons with stroke feel in balance in relation to fear of falling.Implications:In physical therapy practice, the experiences of balance limitations after stroke from the person with stroke add valuable information to various assessments. By asking the person about their abilities and challenges in daily living, rehabilitation interventions can be more individualized and based on the person's actual condition and their wishes and needs.
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| 13. |
- Arvidsson Lindvall, Mialinn, 1977-, et al.
(författare)
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"I can manage the challenge" : a qualitative study describing experiences of living with balance limitations after first-ever stroke
- 2021
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Ingår i: International Journal of Qualitative Studies on Health and Well-being. - : Co-Action Publishing. - 1748-2623 .- 1748-2631. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe experiences of living with balance limitations after first-ever stroke.Materials and methods: This study has a qualitative design, comprising interviews with 19 persons with first-ever stroke, ten women and nine men. Their mean age was 77 years and the mean time since stroke was 15 months. Stroke survivors who were able to walk outdoors with or without a walking aid and who were independent in toileting and dressing were invited to participate. Semi-structured individual interviews were performed. An inductive qualitative content analysis of the manifest and latent content was conducted.Results: The results are presented in two themes illustrating the latent content of the data, "Feeling dizzy and unstable is a continuous challenge" and "Feeling confidence despite dizziness and unsteadiness", and seven categories illustrating the manifest content: Limitations in daily life; Being emotionally affected; The need for physical support; Everything takes time; I can still manage; Feelings of acceptance; and Finding individual solutions.Conclusions: All participants experienced the balance limitations as a continuous challenge in their everyday life, yet they also felt confidence. They had to some degree adapted their activities and were able to manage their daily life.
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| 14. |
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| 15. |
- Arvidsson Lindvall, Mialinn, 1977-, et al.
(författare)
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LIVING WITH BALANCE LIMITATIONS AFTER FIRST-EVER STROKE
- 2020
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Ingår i: International Journal of Stroke. - : Wiley-Blackwell Publishing Asia. - 1747-4930 .- 1747-4949. ; 15:Suppl. 1, s. 257-257
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Stroke is the leading cause of serious, long-term disability among adults. Balance can be limited after stroke and the limitations affect walking and independence in activities of daily living. Having good balance has been described as an important factor in outdoor walking and for participation in exercises. Studies in which persons with stroke describe their experience of balance in everyday life are scarce.Aim: To describe experiences of living with balance limitations after first-ever stroke.Methods: A qualitative design, comprising interviews with 19 persons with first-ever stroke, ten women and nine men, aged between 42–92 years. Inclusion criteria were: having had a first-ever stroke and self-reported impaired balance, unaffected speech, independence in toileting and dressing, and walking ability indoors and outdoors with or without a walking aid. Data was analysed by means of an inductive content analysis covering both the manifest and the latent content of the transcribed interviews.Results: The results are presented in two themes illustrating the latent content of the data. “Feeling dizzy and unstable is a continuous challenge” revolves around participants’ descriptions of balance as a constant feeling of dizziness and unsteadiness. “Feeling trust and confidence despite dizziness and unsteadiness” is about perceived abilities and feelings of confidence about still being able to do things oneself, despite the dizziness and unsteadiness.Conclusion: All participants experienced the balance limitations as a continuous challenge in everyday life, yet they also felt trust and confidence and experienced that they still managed their everyday life.
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| 16. |
- Arvidsson Lindvall, Mialinn, 1977-
(författare)
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Physiotherapeutic perspectives on balance control after stroke : exercises, experiences and measures
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to investigate physiotherapeutic perspectives on balance after stroke, in terms of exercises, experiences and measurements. Study I was a pilot randomized controlled trial with 46 persons who had had a stroke, 24 of whom were included in the intervention group and 22 who were included in the control group. The intervention consisted of 8 weeks of body awareness therapy (BAT). There were no significant differences over time between the groups in the outcome measures of balance, walking, self-reported balance confidence and quality of life. Study II had a qualitative design using content analysis. Participants in the intervention group from Study I and the four physiotherapists who had been in charge of the BAT were interviewed. One overall theme emerged: "Simple yet challenging", which was based on six categories. Study III investigated the validity and test-retest reliability of the Six-Spot Step test (SSST), an instrument used to assess the ability to take load on each leg. A cross-sectional design with 81 persons who had had stroke was performed. The convergent validity was strong to moderate, and the test-retest reliability was good. In Study IV a mixed method design including both qualitative and quantitative data collection was used. The participants’ experiences of balance and its influence in everyday life were presented in two themes: "Feeling dizzy and unstable is a continuous challenge" and "Feeling trust and confidence despite dizziness and unsteadiness". Taken together, the different data sets provided complementary and confirmatory information about balance. All participants experienced the balance limitations as a continuous challenge in everyday life, yet they also felt trust and confidence.In summary, BAT can be a complement in physiotherapeutic stroke rehabilitation and the SSST can be used as a measuring instrument of walking balance in persons with stroke. Living with balance limitations was experienced as a challenge but the participants were still able to manage their everyday life and activities.
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| 17. |
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| 18. |
- Arvidsson Lindvall, Mialinn, 1977-, et al.
(författare)
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Validity and test–retest reliability of the six-spot step test in persons after stroke
- 2020
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Ingår i: Physiotherapy Theory and Practice. - : Taylor & Francis. - 0959-3985 .- 1532-5040. ; 36:1, s. 211-218
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: After stroke, asymmetric weight distribution is common with decreased balance control in standing and walking. The six-spot step test (SSST) includes a 5-m walk during which one leg shoves wooden blocks out of circles marked on the floor, thus assessing the ability to take load on each leg. The aim of the present study was to investigate the convergent and discriminant validity and test–retest reliability of the SSST in persons with stroke. Methods: Eighty-one participants were included. A cross-sectional study was performed, in which the SSST was conducted twice, 3–7 days apart. Validity was investigated using measures of dynamic balance and walking. Reliability was assessed using intraclass correlation coefficient, standard error of the measurement (SEM), and smallest real difference (SRD). Results: The convergent validity was strong to moderate, and the test–retest reliability was good. The SEM% was 14.7%, and the SRD% was 40.8% based on the mean of four walks shoving twice with the paretic and twice with the non-paretic leg. Conclusion: Values on random measurement error were high affecting the use of the SSST for follow-up evaluations but the SSST can be a complementary measure of gait and balance.
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| 19. |
- Baldvinsdóttir, Bryndís, et al.
(författare)
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Adverse events associated with microsurgial treatment for ruptured intracerebral aneurysms: a prospective nationwide study on subarachnoid haemorrhage in Sweden
- 2023
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 94:7, s. 575-580
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAdverse events (AEs) or complications may arise secondary to the treatment of aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to identify AEs associated with microsurgical occlusion of ruptured aneurysms, as well as to analyse their risk factors and impact on functional outcome. MethodsPatients with aneurysmal SAH admitted to the neurosurgical centres in Sweden were prospectively registered during a 3.5-year period (2014-2018). AEs were categorised as intraoperative or postoperative. A range of variables from patient history and SAH characteristics were explored as potential risk factors for an AE. Functional outcome was assessed approximately 1 year after the bleeding using the extended Glasgow Outcome Scale. ResultsIn total, 1037 patients were treated for ruptured aneurysms, of which, 322 patients were treated with microsurgery. There were 105 surgical AEs in 97 patients (30%); 94 were intraoperative AEs in 79 patients (25%). Aneurysm rerupture occurred in 43 patients (13%), temporary occlusion of the parent artery >5 min in 26 patients (8%) and adjacent vessel injury in 25 patients (8%). High Fisher grade and brain oedema on CT were related to increased risk of AEs. At follow-up, 38% of patients had unfavourable outcome. Patients suffering AEs were more likely to have unfavourable outcome (OR 2.3, 95% CI 1.10 to 4.69). ConclusionIntraoperative AEs occurred in 25% of patients treated with microsurgery for ruptured intracerebral aneurysm in this nationwide survey. Although most operated patients had favourable outcome, AEs were associated with increased risk of unfavourable outcome.
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| 20. |
- Bartek, Jiri, Jr., et al.
(författare)
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Scandinavian Multicenter Acute Subdural Hematoma (SMASH) Study : Study Protocol for a Multinational Population-Based Consecutive Cohort
- 2019
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Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 0148-396X .- 1524-4040. ; 84:3, s. 799-803
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDTraumatic acute subdural hematomas (ASDHs) are associated with high rate of morbidity and mortality, especially in elderly individuals. However, recent reports indicate that the morbidity and mortality rates might have improved.OBJECTIVETo evaluate postoperative (30-d) mortality in younger vs elderly (70 yr) patients with ASDH. Comparing younger and elderly patients, the secondary objectives are morbidity patterns of care and 6 mo outcome according to Glasgow outcome scale (GOS). Finally, in patients with traumatic ASDH, we aim to provide prognostic variables.METHODS This is a large-scale population-based Scandinavian study including all neurosurgical departments in Denmark and Sweden. All adult (18 yr) patients surgically treated between 2010 and 2014 for a traumatic ASDH in Denmark and Sweden will be included. Identification at clinicaltrials.gov is NCT03284190.EXPECTED OUTCOMESWe expect to provide data on potential differences between younger vs elderly patients in terms of mortality and morbidity. We hypothesize that elderly patients selected for surgery have a similar pattern of care as compared with younger patients. We will provide functional outcome in terms of GOS at 6 mo in younger vs elderly patients undergoing ASDH evacuation. Finally, clinical useful prognostic factors for favorable (GOS 4-5) vs unfavorable (GOS 1-3) will be identified.DISCUSSION An improved understanding of the clinical outcome, treatment and resource allocation, clinical course, and the prognostic factors of traumatic ASDH will allow neurosurgeons to make better treatment decisions.
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| 21. |
- Bjoreland, Anders, et al.
(författare)
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Liquid ionization chamber calibrated gel dosimetry in conformal stereotactic radiotherapy of brain lesions
- 2008
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 47:6, s. 1099-1109
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Tidskriftsartikel (refereegranskat)abstract
- Hypofractionated conformal stereotactic radiotherapy (HCSRT) is an established method of treating brain lesions such as arteriovenous malformations (AVMs) and brain metastases. The aim of this study was to investigate the reliability of treatment plans in the terms of dose distribution and absorbed dose for HCSRT. Methods and materials. Treatment plans for three different clinical intracerebral targets, AVMs, were transferred to a CT study of a spherical water filled phantom simulating the human head and recalculated for the phantom geometry using a standard treatment planning system utilizing a pencil beam algorithm for dose calculation. The calculated absorbed dose, relative three dimensional (3D) dose distribution and dose conformity were investigated using gel dosimetry normalized to liquid ionization chamber (LIC) measurements. Results. The measured absorbed dose to the dose reference point was found to be within 2% of the calculated dose for all three targets. The measured dose distribution was found to be within 3% and 2 mm of the calculated dose for more than 93% of all points in the target volume for all three targets. Conclusions. The results show that the investigated standard treatment planning system can correctly predict the absorbed dose and dose distribution in different types of intracerebral targets and that the treatment can be delivered according to the plan.
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| 22. |
- Blomstedt, Patric, et al.
(författare)
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Reoperation after failed deep brain stimulation for essential tremor
- 2012
-
Ingår i: World Neurosurgery. - : Elsevier. - 1878-8750. ; 78:5, s. 554.e1-554.e5
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the effects of reoperation with deep brain stimulation (DBS) in the caudal zona incerta (cZi) in patients with failed DBS in the ventral intermediate (Vim) nucleus of the thalamus for essential tremor. METHODS: The results of reoperation with cZi DBS in five patients with failed Vim DBS were retrospectively analyzed. RESULTS: Two patients had early failure of Vim DBS, and three after several years of good effect. The mean deviation from the atlas Vim target point was 1.4 mm. Before the reoperation Vim DBS improved hand function and tremor in the treated hand at 25 %, whereas cZi DBS achieved an improvement of 57%. Although cZi was more efficient than Vim DBS, also in the patients with late failure of Vim DBS, they still exhibited a considerable residual tremor on cZi DBS. CONCLUSIONS: The effect on tremor was, in this small sample population, improved by implanting an electrode in the cZi. The effect was modest in those patients suffering a deterioration years after the initial operation.
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| 23. |
- Bobinski, Lukas, et al.
(författare)
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Complications following cranioplasty using autologous bone or polymethylmethacrylate-Retrospective experience from a single center
- 2013
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Ingår i: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print). - : Elsevier BV. - 0303-8467 .- 1872-6968. ; 115:9, s. 1788-1791
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Tidskriftsartikel (refereegranskat)abstract
- Objective: A decompressive hemicraniectomy is a potentially life-saving intervention following head trauma. Once performed patients are obliged to undergo a second procedure with cranioplasty. Two of the most commonly used materials are autologous bone and polymethylmethacrylate (PMMA). We have now evaluated complications following a cranioplasty using these materials. Materials and methods: During a 7-year period (2002-2008) 49 patients were operated with a decompressive craniectomy following head trauma. Patients received a cranioplasty consisting of autologous bone (30 patients, 61.2%) or PMMA (19 patients, 38.8%) and were followed at least 24 months. Patient data were collected retrospectively. Results: Twenty patients (20/49, 40.8%) experienced a complication that prompted a re-operation. There was a significantly higher rate of complications leading to a re-operation (53.3% vs. 21.1%, p = 0.03) and a shorter survival time of the cranioplasty (mean 48.1 +/- 7.8 vs. 79.5 +/- 9.0 months, p = 0.035) in patients with autologous bone compared to PMMA. Bone resorption and the presence of postoperative hematomas were significantly more common in patients with autologous bone. The material used for cranioplasty was the only variable that significantly correlated to the rate of complications. Conclusions: In our series we had a high percentage of patients needing re-operation due to complications following a cranioplasty. Though generally considered a straightforward procedure, complications and associated morbidity in patients undergoing cranioplasty should not be underestimated.
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| 24. |
- Bobinski, Lukas, 1977-
(författare)
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On evolution of intracranial changes after severe traumatic brain injury and its impact on clinical outcome
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Severe traumatic brain injury (sTBI) is a cause of death and disability worldwide and requires treatment at specialized neuro-intensive care units (NICU) with a multimodal monitoring approach. The CT scan imaging supports the monitoring and diagnostics. The level of S100B and neuron specific enolase (NSE) reflects the severity of the injury. The therapy resistant intracranial hypertension requires decompressive craniectomy (DC). After DC, the cranium must be reconstructed to recreate the normal intracranial physiology as well as to address cosmetic issues. The evolution of the pathological intracranial changes was analyzed in accordance with the three CT classifications: Marshall, Rotterdam and Morris-Marshall. The Rotterdam scale was best in describing the dynamics of the pathological evolution. Both the Rotterdam score and Morris- Marshall classification showed strong correlation with the clinical outcome, a finding that suggests that they could be used for prognostication. We demonstrated a clear correlation between the CT classifications and concentrations of S100B and NSE. The results revealed a concomitant correlation between NSE and S100B and clinical outcome. We found that the interaction between the ICP, Rotterdam CT classification, and concentrations of biochemical biomarkers are all associated with DC. We found a high percentage of complications following cranioplasty. Our results call into question whether custom-made allograft should be considered the best material for cranioplasty. It is concluded that both the Rotterdam and Morris-Marshall classification contribute to clinical evaluation of intracranial dynamics after sTBI, and might be used in combination with biochemical biomarkers for better assessment. The decision to perform DC should include a re-assesment of ICP evolution, CT scan images and concentration of the biochemical biomarkers. Furthermore, when determining whether DC treatment should be used, surgeon should also consider the risks of the following cranioplasty.
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| 25. |
- Brundin, Patrik, et al.
(författare)
-
Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease
- 2000
-
Ingår i: Brain. - 1460-2156. ; 123, s. 1380-1390
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Tidskriftsartikel (refereegranskat)abstract
- Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in 'off' phase was reduced by a mean of 40%. At 10-23 months after grafting, PET showed a mean 61% increase of 6-L-[(18)F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals.
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| 26. |
- Frisk, Peter, et al.
(författare)
-
Decrease of trace elements in erythrocytes and plasma after removal of dental amalgam and other metal alloys
- 2006
-
Ingår i: Biological Trace Element Research. - 0163-4984 .- 1559-0720. ; 113:3, s. 247-259
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to determine the concentration changes of 13 elements in erythrocytes and plasma after the removal of dental amalgam and other metal alloys. Blood samples from 250 patients were collected, separated into erythrocytes and plasma, and analyzed by inductively coupled plasma-mass spectrometry. The 250 patients were divided into 3 groups (Negative, Zero, and Positive) depending on their estimation of quality of life in an earlier study. Magnesium in plasma, selenium and mercury in plasma, and erythrocytes showed decreased concentrations after amalgam removal in all groups (p < 0.05). Titanium in plasma, copper in plasma, and erythrocytes and zinc in plasma exhibited decreased concentrations after amalgam removal in the Negative and Positive groups (p < 0.05). Silver in plasma and gold in erythrocytes decreased in the Zero and Positive groups after amalgam removal (p < 0.05). Copper in erythrocytes and silver and gold in plasma showed higher concentrations after amalgam removal in the Negative compared to the Positive group (p < 0.05), suggesting that patients in the Negative group excrete metals slowly. Moreover, the cobalt levels in plasma were lowest in the Negative group and only this group showed a significant increase in vitamin B12 levels in blood after amalgam removal.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Hagell, Peter, et al.
(författare)
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Dyskinesias following neural transplantation in Parkinson's disease.
- 2002
-
Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 5:7, s. 627-628
-
Tidskriftsartikel (refereegranskat)abstract
- Severe dyskinesias during the 'off' phases (periods of increased Parkinson's disease (PD) disability) have been observed following intrastriatal transplantation of human embryonic mesencephalic tissue. Here we retrospectively analyzed 14 patients who were followed for up to 11 years after grafting, and found that dyskinesias (abnormal involuntary movements and postures) increased during postoperative off phases, but were generally of mild to moderate severity. Dyskinesia severity was not related to the magnitude of graft-derived dopaminergic re-innervation, as judged by (18)F-labeled 6-L-fluorodopa (FD) positron emission tomography (PET), indicating that off-phase dyskinesias probably did not result from excessive growth of grafted dopaminergic neurons.
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| 31. |
- Hagell, Peter, et al.
(författare)
-
Health-related quality of life following bilateral intrastriatal transplantation in Parkinson's disease
- 2000
-
Ingår i: Movement Disorders. - 0885-3185. ; 15:2, s. 224-229
-
Tidskriftsartikel (refereegranskat)abstract
- Intrastriatal transplantation of embryonic dopaminergic tissue is a new, experimental approach for the treatment of Parkinson's disease (PD). Clinical trials have shown longterm graft survival and therapeutically valuable improvements with decreased L-dopa dose and time spent in the "off"-phase, and reduced rigidity and hypokinesia. We have measured health-related quality of life (HRQoL) using the Nottingham Health Profile (NHP) in five patients subjected to bilateral transplantation in the caudate and putamen to explore the influence of intrastriatal grafts on HRQoL and the value of such measures in trials of restorative therapies. The results demonstrate improved HRQoL following transplantation, with individual patients showing striking improvements within different dimensions of the NHP as well as the NHP distress index (NHPD). The most pronounced improvements after grafting were observed for physical mobility along with emotional reactions and energy. These results indicate that intrastriatal transplantation of embryonic dopaminergic tissue can give rise to improvements within most areas of HRQoL, and that HRQoL measurements provide important information additional to that obtained by traditional, symptom-oriented assessment protocols. However, the optimal approach to HRQoL measurement in PD remains to be determined.
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| 32. |
- Hagell, Peter, et al.
(författare)
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Health status measurement in Parkinson's disease : validity of the PDQ-39 and Nottingham Health Profile
- 2003
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Ingår i: Movement Disorders. - : John Wiley & Sons Inc.. - 0885-3185 .- 1531-8257. ; 18:7, s. 773-783
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the feasibility and psychometric properties of two commonly used health status questionnaires in Parkinson's disease (PD): the generic Nottingham Health Profile (NHP) and the disease-specific 39-item Parkinson's disease Questionnaire (PDQ-39), from a cross-sectional postal survey of PD patients (N = 81), using traditional and Rasch measurement methodologies. Overall response rate was 88%. Both questionnaires were found feasible, although the NHP performed less well. The PDQ-39 had fewer floor effects and was better able to separate respondents into distinct groups than the NHP, whereas the latter exhibited less ambiguous dimensionality and better targeting of respondents with non-extreme scores. Reliability and validity indices were similar, and potential differential item functioning by age and gender groups was found for both questionnaires. PDQ-39 response alternatives indicated ambiguity. With few exceptions, questionnaire scales were unable to meet recommended standards fully. While preliminary, this study illustrates the need for thorough evaluation of outcome measures and has implications beyond the questionnaires used here. Although promising, both questionnaires warrant further developmental work and stronger support of measurement validity before they could be considered fully suitable for valid use in PD, in particular in earlier stages of the disease.
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| 33. |
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| 34. |
- Hagell, Peter, et al.
(författare)
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Sequential bilateral transplantation in Parkinson's disease: effects of the second graft
- 1999
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156. ; 122:6, s. 1121-1132
-
Tidskriftsartikel (refereegranskat)abstract
- Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on-off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.
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| 35. |
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| 36. |
- Hjelmgren, Jonas, et al.
(författare)
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Estimating the value of novel interventions for Parkinson's disease: An early decision-making model with application to dopamine cell replacement.
- 2006
-
Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 12:7, s. 443-452
-
Tidskriftsartikel (refereegranskat)abstract
- A long-term cost-effectiveness model for early decision-making and estimation of outcomes of novel therapeutic procedures for Parkinson's disease (PD) was developed based on the Hoehn and Yahr (HY) stages of PD. Results provided support for model validity. Model application to a future dopamine cell replacement therapy indicated long-term cost offsets and gains in quality-adjusted life years (QALYs) in early onset PD (HY III-IV), as compared to standard drug therapy. The maximum price premium (i.e., profit or compensation for developmental costs) for the intervention to remain cost-effective was estimated to EURO12000-64000 according to cost-per-QALY thresholds of EURO38000-70000 and depending on whether all or only medical direct costs are considered. The study illustrates the value of early health economic modeling and the described model shows promise as a means to estimate outcomes and aid decision-making regarding novel interventions for PD. (c) 2006 Elsevier Ltd. All rights reserved.
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| 37. |
- Johansson, Conny, et al.
(författare)
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Serum Levels of Myo-inositol Predicts Clinical Outcome 1 Year After Aneurysmal Subarachnoid Hemorrhage
- 2022
-
Ingår i: Neurosurgery. - : Lippincott Williams & Wilkins. - 0148-396X .- 1524-4040. ; 91:5, s. 790-798
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early prognostication of long-term outcome in patients suffering from spontaneous subarachnoid hemorrhage (SAH) remains a challenge. No biomarkers are routinely used for prognostication. A previous study has indicated that the metabolite myo-inositol (MI) may be used to predict long-term outcome.OBJECTIVE: To investigate if MI measured in serum correlates with long-term clinical outcome in patients suffering from SAH.METHODS: We conducted an observational cohort study including 88 patients treated for SAH at Umeå University Hospital. Serum samples were collected in the hospital, and a gas chromatography/mass spectroscopy method was used to quantitatively measure MI. Patients were assessed after 1 year using the Glasgow Outcome Scale Extended and dichotomized to favorable or unfavorable outcome. Differences in MI levels between the 2 groups were analyzed.RESULTS: There was no difference in MI levels between the groups upon admission. Myo-inositol levels decreased over time in the entire study population. The decrease was significantly larger in the unfavorable outcome group. A receiver operating characteristics analysis yielded an area under the curve of 0.903 (CI 0.8-1.0, P < .001) for the MI value on day 7 to predict favorable outcome after 1 year.CONCLUSION: Myo-inositol measured in serum may aid prognostication of outcome in patients with SAH. The mechanism behind this remains unclear, although it can be theorized to reflect processes leading to delayed cerebral ischemia, which affects long-term outcome. This is the first study to quantitively measure MI in serum for prognostication of outcome in patients with SAH.
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| 38. |
- Johansson, Conny, et al.
(författare)
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Serum neurofilament light as a predictor of outcome in subarachnoid haemorrhage
- 2023
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Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 165:10, s. 2793-2800
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Prognostication of clinical outcome in patients suffering from aneurysmal subarachnoid haemorrhage (SAH) is a challenge. There are no biochemical markers in routine use that can aid in prognostication. Neurofilament light (NFL) measured in cerebrospinal fluid (CSF) has been associated with clinical outcome in previous studies.Objective: To investigate if serum levels of NFL correlate with CSF levels and long-term clinical outcome in patients suffering from SAH.Methods: We conducted an observational cohort study of 88 patients treated for SAH at Umeå University Hospital in 2014–2018. Serum and CSF samples were analysed using an enzyme-linked immunosorbent assay to quantify NFL levels. Outcome was assessed using Glasgow Outcome Scale Extended and dichotomised as favourable or unfavourable. Differences in NFL levels between outcome groups were analysed using repeated measurements ANOVA. Relationship between CSF and serum NFL levels was analysed using Pearson’s correlation. A multivariate binary logistic regression model and a receiver operation characteristic curve were used to assess the predictive value of serum NFL.Results: A significant correlation between serum and CSF-NFL levels could be seen (Pearson’s correlation coefficient = 0.7, p <.0001). Mean level of serum NFL was higher in the unfavourable outcome group than the favourable outcome group (p <.0001), in all epochs of SAH, and correlated with initial disease severity on the World Federation of Neurosurgical Societies scale. Serum NFL in the late phase displayed the best predictive potential in a receiver operation characteristic curve analysis (AUC=0.845, p <.0001).Conclusion: Levels of NFL in serum and CSF are correlated. Early serum NFL levels seem to reflect initial tissue damage and serum NFL levels in the late phase may reflect secondary events such as vasospasm or delayed cerebral ischemia. Serum NFL may be used as a prognostic marker of clinical outcome in SAH.
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| 39. |
- Kalén, Peter, et al.
(författare)
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Hippocampal Noradrenaline and Serotonin Release over 24 Hours as Measured by the Dialysis Technique in Freely Moving Rats : Correlation to Behavioural Activity State, Effect of Handling and Tail-Pinch
- 1989
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 1:3, s. 181-188
-
Tidskriftsartikel (refereegranskat)abstract
- Hippocampal extracellular levels of noradrenaline (NA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were monitored with the microdialysis technique in freely moving rats. In one experiment 30 min samples were collected during 24 h of continuous perfusion, and the monoamine output was compared to the behavioural activity state, as arbitrarily classified in three categories: sleep/rest, drowsiness and full alertness associated with complex behaviours. In the individual animal the hippocampal NA and 5-HT output showed pronounced fluctuations during the 24 h period, but the 30 min sampling times did not allow for a clear-cut correlation to behavioural activity state. However, the mean NA and 5-HT output for all animals during the dark period of the day was 43 and 38% higher, respectively, than during the light period, and the average NA and 5-HT levels in samples collected during periods of high behavioural activity was 34 and 45% higher, respectively, than during periods of rest or sleep. In contrast, there were no detectable changes in extracellular 5-HIAA. The selective serotonin uptake blocker indalpine, added to the perfusion fluid at 1 microM, increased the extracellular 5-HT levels 6-fold, with a similar correlation to behavioural activity state as without indalpine. In a second experiment the effect of handling and tail-pinch was studied in 15 min sample fractions. Gentle handling of the animals during the sampling period increased the hippocampal NA and 5-HT output by 32 and 72%, respectively, and a similar increase (63 and 48%) was obtained by application of tail-pinch. Maximum NA output was reached during the handling or tail-pinch period, whereas maximal 5-HT levels were detected in the subsequent 15 min sample fraction. No changes in extracellular 5-HIAA was observed. It is concluded (1) that intracerebral microdialysis provides a useful method for the study of extracellular NA and 5-HT in the hippocampal formation of conscious rats during active behaviour; (2) that there are substantial fluctuations in hippocampal NA and 5-HT output in freely moving rats which correlate with the light - dark cycle as well as with the activity state of the animals; (3) that the spontaneous variations in 5-HT output are maintained during reuptake blockade; and (4) that behavioural activation through gentle handling or tail-pinch elicits NA and 5-HT release. The present data support a role of the forebrain NA and 5-HT systems in behavioural state control and highlights the necessity of experimental designs in which the spontaneous fluctuations in transmitter release are controlled for in studies of, for example, drug effects on NA and 5-HT release in conscious animals.
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| 40. |
- Kalén, Peter, et al.
(författare)
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Host Brain Regulation of Fetal Locus Coeruleus Neurons Grafted to the Hippocampus in 6-Hydroxydopamine-Treated Rats. An Intracerebral Microdialysis Study
- 1991
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 3:9, s. 905-918
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Tidskriftsartikel (refereegranskat)abstract
- Release properties of intrahippocampal transplants of noradrenergic neurons were monitored by microdialysis in awake and halothane-anaesthetized rats. Fetal locus coeruleus neurons were implanted as a cell suspension into hippocampi deprived of their innate noradrenalin (NA) innervation by intraventricular 6-hydroxydopamine treatment. Dialysis probes of the loop type were implanted into the dorsal hippocampus 1 - 2 days before each experiment, i.e. 7 - 11 months after grafting. Age-matched intact and lesion-only animals served as controls. Microscopic analysis showed a graft-derived tyrosine hydroxylase immunoreactive, presumably noradrenergic, fibre network throughout the dorsal hippocampal formation, surrounding the probe site. The innervation density varied from sub- to supranormal. The grafts restored baseline NA release in the graft-reinnervated hippocampus to near-normal levels both in awake and halothane-anaesthetized animals. Potassium chloride (100 mM) in the perfusion fluid induced a dramatic increase in NA release that was similar in magnitude in the grafted and intact hippocampi. A NA uptake blocker (desipramine) added to the perfusion fluid at 5 microM induced a similar increase in NA output in the grafted and intact hippocampi, and the output was substantially reduced by tetrodotoxin, added at 1 microM in the presence of uptake blockade. Electrical stimulation of the lateral habenular nucleus (15 Hz, 0.5 mA) in halothane-anaesthetized rats induced a significant increase in NA output both in the intact and grafted hippocampi. This effect was abolished by transection of the fasciculus retroflexus, which carries the efferent projections of the habenular complex. Behavioural activation through handling induced a consistent increase in NA release only in the intact animals, but in a few grafted rats (which also responded to habenular stimulation) the NA output was clearly elevated by handling. Forced immobilization induced a significant increase in NA output both in the intact and grafted hippocampi, but in the grafted ones the response was somewhat smaller and more transient. In the same set of animals, swimming in warm water (25 - 30 degrees C) induced a sharp increase in NA output in the intact animals, whereas only one of the grafted rats responded by increased NA output. The results indicate that the locus coeruleus grafts, despite their ectopic location, can become functionally integrated with the host brain, and that the activity of the transplanted noradrenergic neurons can, under some circumstances, be modulated from the host brain in response to environmental challenges.
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| 41. |
- Kilbo Edlund, Karl, et al.
(författare)
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High-resolution dispersion modelling of PM2.5, PM10, NOx and NO2 exposure in metropolitan areas in Sweden 2000‒2018 – large health gains due to decreased population exposure
- 2024
-
Ingår i: Air Quality, Atmosphere and Health. - 1873-9318 .- 1873-9326.
-
Tidskriftsartikel (refereegranskat)abstract
- Ambient air pollution remains the major environmental cause of disease. Accurate assessment of population exposure and small-scale spatial exposure variations over long time periods is essential for epidemiological studies. We estimated annual exposure to fine and coarse particulate matter (PM2.5, PM10), and nitrogen oxides (NOx, NO2) with high spatial resolution to examine time trends 2000‒2018, compliance with the WHO Air Quality Guidelines, and assess the health impact. The modelling area covered six metropolitan areas in Sweden with a combined population of 5.5 million. Long-range transported air pollutants were modelled using a chemical transport model with bias correction, and locally emitted air pollutants using source-specific Gaussian-type dispersion models at resolutions up to 50 × 50m. The modelled concentrations were validated using quality-controlled monitoring data. Lastly, we estimated the reduction in mortality associated with the decrease in population exposure. The validity of modelled air pollutant concentrations was good (R2 for PM2.5 0.84, PM10 0.61, and NOx 0.87). Air pollution exposure decreased substantially, from a population weighted mean exposure to PM2.5 of 12.2µgm−3 in 2000 to 5.4µgm−3 in 2018. We estimated that the decreased exposure was associated with a reduction of 2719 (95% CI 2046–3055) premature deaths annually. However, in 2018, 65%, 8%, and 42% of residents in the modelled areas were still exposed to PM2.5, PM10, or NO2 levels, respectively, that exceeded the current WHO Air Quality Guidelines for annual average exposure. This emphasises the potential public health benefits of reductions in air pollution emissions.
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| 42. |
- Kokaia, Merab, et al.
(författare)
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Seizure suppression in kindling epilepsy by intracerebral implants of GABA- but not by noradrenaline-releasing polymer matrices
- 1994
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Ingår i: Experimental Brain Research. - 0014-4819. ; 100:3, s. 385-394
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Tidskriftsartikel (refereegranskat)abstract
- Gamma-aminobutyric acid (GABA)-releasing polymer matrices were implanted bilaterally, immediately dorsal to the substantia nigra, in rats previously kindled in the amygdala. Two days after implantation, rats with GABA-releasing matrices exhibited only focal limbic seizures in response to electrical stimulation, whereas animals with control matrices devoid of GABA had generalized convulsions. GABA release from the polymer matrices was high during the first days after implantation, as demonstrated both in vitro and, using microdialysis, in vivo. The anticonvulsant effect was no longer observed at 7 and 14 days at which time GABA release was found to be low. In a parallel experiment, polymer matrices containing noradrenaline (NA) were implanted bilaterally into the hippocampus of rats with extensive forebrain NA depletion induced by an intraventricular 6-hydroxydopamine injection. No effect on the development of hippocampal kindling was observed, despite extracellular NA levels exceeding those of rats with intrahippocampal locus coeruleus grafts that have previously been shown to retard kindling rate. The results indicate that GABA-releasing implants located in the substantia nigra region can suppress seizure generalization in epilepsy, even in the absence of synapse formation and integration with the host brain. In contrast, the failure of NA-releasing polymer matrices to retard the development of seizures in NA-depleted rats suggests that such an effect can only be exerted by grafts acting through a well-regulated, synaptic release of NA.
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| 43. |
- Lahtinen, Markus, et al.
(författare)
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Framväxten av ett nytt utbildningslandskap – några digitaliseringsexempel
- 2017
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Konferensbidrag (refereegranskat)abstract
- Utvecklingen av världen, ekonomier och städer hänger idag nära samman med den ökade digitaliseringen. Men den tekniska utvecklingen påverkar även förutsättningarna för utbildning och forskning. Idag växer det tack vare ny teknik fram nya distributionsformer och arenor för kunskapsinhämtning som ger upphov till ett förändrat utbildningslandskap på alla plan. Presentationen innehåller erfarenheter från Malmö högskolas arbete med uppdragsutbildning, utvecklandet av en global distanskurs (MOOC) på Ekonomihögskolan vid Lunds universitet samt tankarna som styrt utvecklingen av ett kommande utbildningsprogram på Uppsala universitet på temat digital affärsutveckling.
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| 44. |
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| 45. |
- Li, Jia-Yi, et al.
(författare)
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Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation.
- 2008
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 14, s. 501-503
-
Tidskriftsartikel (refereegranskat)abstract
- Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11-16 years) developed alpha-synuclein-positive Lewy bodies in grafted neurons. Our observation has key implications for understanding Parkinson's pathogenesis by providing the first evidence, to our knowledge, that the disease can propagate from host to graft cells. However, available data suggest that the majority of grafted cells are functionally unimpaired after a decade, and recipients can still experience long-term symptomatic relief.
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| 46. |
- Lindahl, Bernt, et al.
(författare)
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Health literacy is independently and inversely associated with carotid artery plaques and cardiovascular risk
- 2020
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Ingår i: European Journal of Preventive Cardiology. - : Sage Publications. - 2047-4873 .- 2047-4881. ; 27:2, s. 209-215
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Health literacy, the degree to which individuals understand and act upon health information, may have a pivotal role in the prevention of cardiovascular disease (CVD), with low health literacy potentially explaining poorer adherence to prevention guidelines. We investigated the associations between health literacy, ultrasound-detected carotid atherosclerosis and cardiovascular risk factors.Methods: Baseline data (cross-sectional analysis) from a randomized controlled trial, integrated within the Västerbotten Intervention Program, Northern Sweden, was used. We included 3459 individuals, aged 40 or 50 years with ≥1 conventional risk factor or aged 60 years old. The participants underwent clinical examination, blood sampling, carotid ultrasound assessment of intima-media wall thickness (CIMT) and plaque formation, and answered a questionnaire on health literacy – the Brief Health Literacy Screen. The European Systematic Coronary Risk Evaluation and Framingham Risk Score were calculated.Results: About 20% of the participants had low health literacy. Low health literacy was independently associated with the presence of ultrasound-detected carotid artery plaques after adjustment for age and education, odds ratio (95% confidence interval) 1.54 (1.28–1.85), demonstrating a similar level of risk as for smoking. Health literacy was associated with CIMT in men. Low health literacy was associated with higher CVD risk scores. Sensitivity analyses with low health literacy set to 9% or 30% of the study sample, respectively, yielded essentially the same results.Conclusions: Low health literacy was independently associated with carotid artery plaques and a high level of CVD risk scores. Presenting health information in a fashion that is understood by all patients may improve preventive efforts.
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| 47. |
- Lindgren, Cecilia, 1958-, et al.
(författare)
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ADMA Levels and Arginine/ADMA Ratios Reflect Severity of Disease and Extent of Inflammation After Subarachnoid Hemorrhage
- 2014
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Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 21:1, s. 91-101
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Tidskriftsartikel (refereegranskat)abstract
- Subarachnoid hemorrhage (SAH) is characterized by an inflammatory response that might induce endothelial dysfunction. The aim of this study was to evaluate if ADMA and arginine/ADMA ratios after SAH (indicators of endothelial dysfunction) are related to clinical parameters, inflammatory response, and outcome. Prospective observational study. ADMA, arginine, C-reactive protein (CRP), and cytokines were obtained 0-240 h (h) after SAH. Definition of severe clinical condition was Hunt&Hess (H&H) 3-5 and less severe clinical condition H&H 1-2. Impaired cerebral circulation was assessed by clinical examination, transcranial doppler, CT-scan, and angiography. Glasgow outcome scale (GOS) evaluated the outcome. Compared to admission, 0-48 h after SAH, the following was observed 49-240 h after SAH; (a) ADMA was significantly increased at 97-240 h (highest 217-240 h), (b) CRP was significantly increased at 49-240 h (highest 73-96 h), (c) interleukin-6 (IL-6) was significantly lower at 97-240 h (highest 49-96 h), p < 0.05. ADMA, CRP, and IL-6 were significantly lower and peak arginine/ADMA ratio was significantly higher in patients with H&H 1-2 compared to patients with H&H 3-5, p < 0.05. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with (55 %) or without (45 %) signs of impaired cerebral circulation. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with GOS 1-3 and patients with GOS 4-5. ADMA increased significantly after SAH, and the increase in ADMA started after the pro-inflammatory markers (CRP and IL-6) had peaked. This might indicate that endothelial dysfunction, with ADMA as a marker, is induced by a systemic inflammation.
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| 48. |
- Lindgren, Cecilia, et al.
(författare)
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Cortisol levels are influenced by sedation in the acute phase after subarachnoid haemorrhage
- 2013
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 57:4, s. 452-460
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a life-threatening condition that may be aggravated by acute pituitary damage and cortisol insufficiency. Robust diagnostic criteria for critical illness-related corticosteroid insufficiency (CIRCI) are lacking. The aim of this study was to assess the frequency of CIRCI in the acute phase (0-240 h) after SAH and to evaluate associations between cortisol levels and clinical parameters (sedation, circulatory failure, gender, age, severity of disease, treatment). CIRCI was defined as a single morning serum cortisol (mSC) < 200 nmol/L. The lower limit for calculated free cortisol (cFC) was set at < 22 nmol/L, and for saliva cortisol at < 7.7 nmol/L.METHODS: Fifty patients were included. Serum/saliva cortisol and corticosteroid-binding globulin were obtained every second morning. A logistic regression model was used for multivariate analysis comparing cortisol levels with clinical parameters.RESULTS: Of the patients, 21/50 (42%) had an mSC < 200 nmol/L and 30/50 (60%) had a cFC < 22 nmol/L. In patients with continuous intravenous sedation, the odds ratio for a mSC to be < 200 nmol/L was 18 times higher (95% confidence interval 4.2-85.0, P < 0.001), and the odds ratio for a cFC to be < 22 nmol/L was 2.4 times higher (95% confidence interval 1.2-4.7, P < 0.05) compared with patients with no continuous intravenous sedation.CONCLUSIONS: Continuous intravenous sedation was significantly associated with cortisol values under defined limits (mSC < 200, cFC < 22 nmol/L). The possibility that sedating drugs per se may influence cortisol levels should be taken into consideration before CIRCI is diagnosed.
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| 49. |
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| 50. |
- Lindvall, Olle, et al.
(författare)
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Cell replacement therapy in human neurodegenerative disorders
- 2002
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Ingår i: Clinical Neuroscience Research. - 1873-779X. ; 2:1-2, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- Clinical studies with intrastriatal transplants of embryonic mesencephalic tissue in patients with Parkinson's disease (PD) provide proof-of-principle for the cell replacement strategy in the diseased human brain. The grafted dopaminergic neurons can reinnervate the denervated striatum, restore regulated dopamine release and movement-related frontal cortical activation, and give rise to significant symptomatic relief. In the most successful cases, patients have been able to withdraw L-DOPA treatment after transplantation and resume an independent life. However, it is unlikely that transplantation of human primary embryonic tissue can be developed into therapies for large numbers of patients. Stem cells could be useful as an unlimited source of specific neuron types, e.g. dopamine neurons. So far, neurons with at least some dopaminergic characteristics have been generated from stem cells. However, their survival after grafting in animal models has been poor and it is also unclear if they function as normal dopamine neurons. It is important to emphasize that the biological problems which have to be solved in order to develop stem cell-based therapies for neurodegenerative disorders like PD are complex and should not be underestimated. Progress should therefore be made with great care.
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