| 1. |
- Sandstrom, Maria, et al.
(författare)
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A Retrospective Evaluation of Bevacizumab Treatment in Patients with Progressive Malignant Glioma in Northern Sweden
- 2017
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 37:4, s. 1869-1874
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Overall survival for glioblastoma patients is short. Standard treatment is surgery followed by radiochemotherapy and adjuvant temozolomide. The aim of this study was to evaluate the outcome for all patients with progressive disease treated with bevacizumab-based treatment combinations in the northern region of Sweden. Patients and Methods: This was a single-center retrospective analysis after bevacizumab-based second-line treatment for malignant glioma. All patients treated with bevacizumab, between 2007 and 2011 in our Center were retrospectively evaluated. Results: Progression-free survival after the start of bevacizumab-based treatment was 20 weeks and overall survival was 31 weeks. Treatment was well tolerated, but 9% of patients (n=6) suffered from serious adverse events. In 68% of patients, a >= 25% decrease in contrast enhancement was seen at best response. Conclusion: Results from this retrospective study are comparable with earlier phase-II. studies and motivate randomized trials of bevacizumab-based treatment in the second-line setting.
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| 2. |
- de Flon, Pierre, et al.
(författare)
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Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab
- 2016
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Ingår i: Neurology. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 87:2, s. 141-147
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the effects of switching treatment from ongoing first-line injectable therapies to rituximab on inflammatory activity measured by MRI and levels of CSF neurofilament light chain (CSF-NFL) in a cohort of patients with clinically stable relapsing-remitting multiple sclerosis (RRMS).Method: Seventy-five patients with clinically stable RRMS treated with the first-line injectables interferon-β (IFN-β) and glatiramer acetate (GA) at 3 Swedish centers were switched to rituximab in this open-label phase II multicenter study. After a run-in period of 3 months, 2 IV doses of 1,000 mg rituximab were given 2 weeks apart followed by repeated clinical assessment, MRI, and CSF-NFL for 24 months.Results: The mean cumulated number of gadolinium-enhancing lesions per patient at months 3 and 6 after treatment shift to rituximab was reduced compared to the run-in period (0.028 vs 0.36, p = 0.029). During the first year after treatment shift, the mean number of new or enlarged T2 lesions per patient was reduced (0.01 vs 0.28, p = 0.004) and mean CSF-NFL levels were reduced by 21% (p = 0.01).Conclusions: For patients with RRMS, a treatment switch from IFN or GA to rituximab is associated with reduced inflammatory activity measured by MRI and CSF-NFL.Classification of evidence: This study provides Class IV evidence that rituximab has an equal or superior effect in reducing inflammatory activity in RRMS measured by MRI and CSF-NFL compared to first-line injectables during the first year after treatment shift.
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| 3. |
- Rönnqvist, Louise, et al.
(författare)
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Effects of twin-births on IQ, handedness, and brain volumes in 8-years-old preterm born twins and matched singletons: a pilot study
- 2016
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Ingår i: Developmental Medicine & Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 58:S6, s. 57-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children born preterm have a high prevalence of long-term cognitive and behavioral disturbances. Still, studies of how preterm-twin-births may effect brain maturation and thus, contribute to long-term effects on brain-behavioral development and functions are rare.Aim: To investigate whether brain volumes differ between twin (TPB) and singleton preterm born (SPB) and full-term born children (FTB) and associate to long-term cognitive and behavioral outcomes as well as to gestational age (GA), birth weight (BW) and head circumference (BHC) at birth.Method: A sample of 22 twin born preterm (Mean GA=32.1, BW=1781), 23 matched singletons preterm (Mean GA=31.8, BW=1751), and 22 full-term singletons were included. All children were investigated by means of their cognition functions (WISC-IV), handedness performance index and brain volumes (3 Tesla MRI) at early school ages (M=7.8y) in 40 children (9 TPB, 10 SPB, 21 FTB).Results: The FTB-children performed better than both TPB and SPB on cognitive performance, and showed higher IQ. Brain volumes, especially Gray matter were stronger associated with IQ in the twins. Furthermore it was found that the SPB singletons had smaller Total Brain volume and less Grey Matter than FTB. The twins showed a higher prevalence of non-right handedness associated to GA, than both SPB and FTB. Independently of birth status, GA, BW and BHC were found to correlate positively with IQ, Total Brain volume, and Gray-and White matter volumes.Conclusion: Discordant handedness in TPB children and associations to lower GA indicate effect of twin-births on early functional laterality. The overall associations found between low GA/BW and smaller BHC at birth in preterm born and associations with lower IQ and smaller brain volumes at 8-y indicate that a very preterm birth are a higher predictor for long-term effects on brain development and cognitive performance than twin-birth per se.
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| 4. |
- Vågberg, Mattias, et al.
(författare)
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Brain parenchymal fraction in an age-stratified healthy population : determined by MRI using manual segmentation and three automated segmentation methods
- 2016
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Ingår i: Journal of neuroradiology. - : Masson Editeur. - 0150-9861 .- 1773-0406. ; 43:6, s. 384-391
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Brain atrophy is a prominent feature in many neurodegenerative diseases, such as multiple sclerosis, but age-related decrease of brain volume occurs regardless of pathological neurodegeneration. Changes in brain volume can be described by use of the brain parenchymal fraction (BPF), most often defined as the ratio of total brain parenchyma to total intracranial space. The BPF is of interest both in research and in clinical practice. To be able to properly interpret this variable, the normal range of BPF must be known. The objective of this study is to present normal values for BPF, stratified by age, and compare manual BPF measurement to three automated methods. MATERIALS AND METHODS: The BPFs of 106 healthy individuals aged 21 to 85 years were determined by the automated segmentation methods SyMap, VBM8 and SPM12. In a subgroup of 54 randomly selected individuals, the BPF was also determined by manual segmentation. RESULTS: The median (IQR) BPFs of the whole study population were 0.857 (0.064), 0.819 (0.028) and 0.784 (0.073) determined by SyMap, VBM8 and SPM12, respectively. The BPF decreased with increasing age. The correlation coefficients between manual segmentation and SyMap, VBM8 and SPM12 were 0.93 (P<0.001), 0.77 (P<0.001) and 0.56 (P<0.001), respectively. CONCLUSIONS: There was a clear relationship between increasing age and decreasing BPF. Knowledge of the range of normal BPF in relation to age group will help in the interpretation of BPF data. The automated segmentation methods displayed varying degrees of similarity to the manual reference, with SyMap being the most similar.
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| 5. |
- Svenningsson, Anders, et al.
(författare)
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Rapid depletion of B lymphocytes by ultra-low-dose rituximab delivered intrathecally
- 2015
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 2332-7812. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We are conducting an open-label phase 1b study on the efficacy of intrathecal (IT) administration of rituximab, provided via an Ommaya reservoir, for the treatment of progressive multiple sclerosis (PMS). The objective of this initial study was to monitor B lymphocytes in peripheral blood (PB) and CSF from the first 10 patients 1 year posttreatment.Methods: Dose titration was performed with daily escalation from 1 mg to 25 mg IT rituximab (n=3). Lymphocyte subpopulations were monitored daily during dose escalation in PB by flow cytometry and subsequently every 3 months for 1 year, after a total dose of 3 x 25 mg. PB B-lymphocyte subpopulations for the remaining patients (n = 7) were monitored at regular intervals. CSF lymphocyte subpopulations for all patients were monitored by flow cytometry every 2-3 months.Results: The PB B-lymphocyte count dropped rapidly after the first 2 injections (total dose of 3.5 mg IT rituximab) to undetectable levels. Three 25-mg doses given once per week depleted peripheral B lymphocytes entirely for the following 3-6 month period.Conclusions: Monoclonal antibodies seem to rapidly redistribute to the peripheral compartment following IT injection. Ultra-low doses of rituximab given IT are sufficient to cause complete depletion of peripheral B lymphocytes, indicating that low-dose IT treatment has the potential to be effective in both the CNS and systemic compartments.Classification of evidence: This study provides Class IV evidence that for patients with PMS, rituximab provided via an Ommaya reservoir depletes peripheral blood B lymphocytes.
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| 6. |
- Rönnqvist, Louise, et al.
(författare)
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Long term effects of preterm births : associations between upper-limb kinematics, brain volumes and cognitive functions
- 2014
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Konferensbidrag (refereegranskat)abstract
- INTRODUCTION and AIM: Studies of long-term outcomes linked to a preterm birth have generally found increasing amount of neurodevelopmental and cognitive disabilities and delays. Still, few have addressed the upper-limb performance by means of kinematic outcomes in associations with cognitive functions and brain volumes. Thus, the main aim of this study was to investigate such possible relationships within school age preterm born children and in relation to their gestational age (GA) at birth.PATIENTS/MATERIALS and METHODS: The present study is part of a longitudinal, ongoing multidisciplinary project with the goal to discover possible long-term effects of a preterm birth. In this sub-study 7-9-years-old children born preterm (PT) without early sign of neuropathology (N= 24, Mean GW=32, range 22-35) in comparison to age matched term born children (N=31) was included. Kinematics was measured by ProReflex, 3D-registration during task specific, bi- and uni-manual upper-limb movement performance. Additionally, functional brain volumes were investigated by 3-Tesla (T) magnetic resonance imaging (MRI) and cognitive functions by the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV).RESULTS: Our preliminary results show significant poorer upper-limb kinematics with more segmented and longer movement paths in the PT-born children in comparison to the term born, this was particular evident for thus children born very- and extremely PT (<32 GA). In agreement with this finding, a decreased total brain volume and regional gray matter reduction were significantly correlated with more segmented arm and head movement trajectories, and with poorer general IQ outcomes, as well as with lower gestational ages.DISCUSSION and CONCLUSIONS: The findings from the present study show that a preterm birth, and especially a very- and extremely preterm birth, may cause long-term effects on the development of neurophysiology mechanism involved in the goal-directed upper-limb movements. Additionally, it shows that the development of the neuro-motor mechanisms also are associated with both cognitive functions and the general brain development. Thus, indicating that a very preterm birth seemingly still give neuro-developmental related problems when at school age.
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| 7. |
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| 8. |
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| 9. |
- Tollin, Clas, 1945-
(författare)
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Rågångar, gränshallar och ägoområden : rekonstruktion av fastighetsstruktur och bebyggelseutveckling i mellersta Småland under äldre medeltid
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation treats settlement development in central Province Småland during the period AD 1050-1350. The choice of study area was dictatedby a wish to find an alternative regional geographical perspective to aboveall eastern Central Sweden.Thetransition from prehistoric to medieval agriculture is mirrored in theproperty domains of the settlement areas. Large property domains apparentlyrepresent an older form of production with thralls, serfs and other subjects as labour force, while smallproperty domains signify household-based family farms.Through information in charters about stewards (brytar), freed thralls, high purchase sums etc. it can beshown that there was a considerable number of large estates withsubservient crofts in Småland as late as the end of the thirteenth century. There is also an obviouslink between the medieval large estates and the central domains of thecommons of the seventeenth and eighteenth centuries (skogelag).It is shown that younger property domains throughout were smaller thanolder ones. Large ownership territories were an expression of large-scalefarming based on more or less enslaved labour while the smaller units represented single-household farms. Avillagization of large estates occurred during the second half of thefourteenth and the fifteenth centuries.The explanation for the settlement development and the agrarianexpansion during the Early Middle Ages should be sought in a complex of legal and institutional innovations. One such occurrence was the establishmentof a systematized tenant institution and of basic taxes tied to the land. Apparently the family farm was superior tothe large estates both for the landowners and for the tillers, a fact thatexplains the high acceptance of the agro-technical innovations which helpedincrease both agricultural production and productivity.
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