| 41. |
- Asplund, Pär, et al.
(författare)
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One hundred eleven Percutaneous Balloon Compressions for Trigeminal Neuralgia in a Cohort of 66 Patients with Multiple Sclerosis
- 2019
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Ingår i: Operative Neurosurgery. - : Oxford University Press. - 2332-4252 .- 2332-4260. ; 17:5, s. 452-459
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Trigeminal neuralgia associated with multiple sclerosis (MS-TN) is comparatively rare and larger series of percutaneous balloon compression (PBC) in such cases are few in the literature.OBJECTIVE: To evaluate the results after PBC for MS-TN with regards to therapeutic effect, side effects, and complications.METHODS: One hundred eleven procedures with PBC performed in 66 cases of MS-TN were analyzed. Therapeutic effect was measured as postoperative time to pain recurrence without medication. All complications were compiled and the sensory function was evaluated in a subgroup of cases.RESULTS: The initial pain free rate was 67% and the median time to pain recurrence was 8 mo. Thirty-six patients were treated with PBC only, and among them, the results were worse if treated 3 to 4 times before, compared to first treatment (P = .009-.034). Patients who had several PBCs had worse results already after the first surgery (P < .001). A significant number of patients had impaired sensation to light touch directly after surgery, which was normalized at the late follow-up. Sensimetric testing showed raised thresholds for perception and pain directly after surgery (P = .004-.03), but these were also normalized at the late follow-up.CONCLUSION: PBC is a treatment that can be effective for many patients with MS-TN. Repeated previous surgeries is a risk factor for an unsatisfactory outcome. However, the patients with multiple surgeries had less satisfactory results already at the first procedure, indicating that a therapy resistant disease can be predicted after the first two PBCs. Postoperative sensory deficits were common but not lasting.
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| 42. |
- Atterhög, Mikael, 1962-
(författare)
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The effect of competition and ownership policies on the housing market
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation consists of five studies presented in seven essays. The overall objectives are to investigate the extent and consequences of competition on the rental housing market as well as the importance of national government policies for the substitute good, i.e. owner-occupied housing. However, each essay also has specific objectives. Due to the characteristics of the housing market, one should not expect competition to be very fierce. The market characteristics are, for instance, capital-intensive, complicated and time-consuming construction processes as well as a limited supply of land in many areas. In fact, firms have a lot to gain from colluding and to avoid e.g. price wars. It is therefore theoretically more likely that housing companies will engage in “functional” or “strategic” competition such as the quality of housing services. Essay I and IV analyze the unique municipal housing market in Sweden where apartment rents are determined by negotiations between the local municipal company and the local Union of Tenants. A regression analysis is applied on data from 30 municipalities. There was a strong correlation between apartment rents at local municipal markets and the level of “external” competition (measured by the price level on the market for single-family owner occupied housing), but not with “internal” competition (measured by the market share of the municipal housing company) or the capital expenditure of the municipal housing company (presumed to reflect historical construction and renovation costs for the apartments). The dissertation also investigates the consequences on rents (essay II) and on the quality of housing services (essay III) from a local Swedish municipal housing company selling a substantial part of its apartment stock (15-40 percent) and thereby theoretically creating more competition. These essays use a quasi-experimental methodology whereby the development of the housing market in a privatization town is compared with the development in a very similar comparison town. It is found that privatization has lead to lower rents in the short- and medium-term in six out of seven privatization towns. The development of the quality of housing services was more related to the performance of each individual company and not a specific category of companies. In essay V, these results are merged and developed further. Essay VI presents a wide range of policies available for governments wishing to increase access to home ownership for low-income households and thereby increasing the pressure on rental housing companies to reduce rents. A systematic overview of policies is provided based on the four distinct time periods of a typical ‘housing career’ of a household; i.e. down payment accumulation stage, transaction stage, ownership stage and selling stage. It is found that many policies are required to meet the specific and differing needs of households for governments wishing to encourage home ownership. Essay VII describes that home ownership rates have increased in almost all industrialized countries during the period from World War II until mid-1990s. The essay analyses the implications of government policies and some other factors (e.g. national wealth, income distribution) on home ownership rates in 13 industrialized countries during the period 19702000. A fixed-effect model is applied on a panel data set. The most important result is that a statistically significant and positive correlation between government support and home ownership rates was found although this is only a preliminary conclusion since data was scarce.
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| 43. |
- Belin, Andrea Carmine, et al.
(författare)
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Association study of two genetic variants in mitochondrial transcription factor A (TFAM) in Alzheimer's and Parkinson's disease.
- 2007
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Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 420:3, s. 257-62
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial (mt) dysfunction has been implicated in Alzheimer's (AD) and Parkinson's disease (PD). Mitochondrial transcription factor A (TFAM) is needed for mtDNA maintenance, regulating mtDNA copy number and is absolutely required for transcriptional initiation at mtDNA promoters. Two genetic variants in TFAM have been reported to be associated with AD in a Caucasian case-control material collected from Germany, Switzerland and Italy. One of these variants was reported to show a tendency for association with AD in a pooled Scottish and Swedish case-control material and the other variant was reported to be associated with AD in a recent meta-analysis. We investigated these two genetic variants, rs1937 and rs2306604, in an AD and a PD case-control material, both from Sweden and found significant genotypic as well as allelic association to marker rs2306604 in the AD case-control material (P=0.05 and P=0.03, respectively), where the A-allele appears to increase risk for developing AD. No association was observed for marker rs1937. We did not find any association in the PD case-control material for either of the two markers. The distribution of the two-locus haplotype frequencies (based on rs1937 and rs2306604) did not differ significantly between affected individuals and controls in the two sample sets. However, the global P-value for haplotypic association testing indicated borderline association in the AD sample set. Our data suggests that the rs2306604 A-allele could be a moderate risk factor for AD, which is supported by the recent meta-analysis.
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| 44. |
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| 45. |
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| 46. |
- Björklund, Kristina, et al.
(författare)
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Different metabolic predictors of white-coat and sustained hypertension over a 20-year follow-up period : a population-based study of elderly men
- 2002
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 106:1, s. 63-68
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Tidskriftsartikel (refereegranskat)abstract
- Background— The clinical significance of white-coat hypertension is still unclear. Moreover, no study has examined metabolic predictors of white-coat versus sustained hypertension. Methods and Results— We investigated men (n=602) in a longitudinal population-based cohort who at age 70 years were identified as normotensive, white-coat hypertensive (office blood pressure [BP] ≥140/90 and daytime ambulatory BP <135/85 mm Hg), and sustained hypertensive (office BP ≥140/90 and daytime ambulatory BP ≥135/85 mm Hg). At baseline, when the subjects were aged 50 years, blood glucose, insulin, lipids, and fatty acid composition of the serum cholesterol esters were analyzed. The investigations at age 70 years included determination of insulin sensitivity and target organ damage. At age 50 years, individuals who 20 years later were identified as white-coat hypertensive or sustained hypertensive showed significantly elevated BP, heart rate, and impaired glucose tolerance compared with normotensive subjects but white coat hypertensive subjects were leaner and had a more favorable serum cholesterol ester fatty acid profile than did sustained hypertensive subjects. At age 70 years, both white-coat and sustained hypertensive subjects showed an impaired insulin sensitivity, elevated blood glucose, and increased serum insulin and heart rate compared with normotensive subjects, but left ventricular mass and urinary albumin excretion were increased only in sustained hypertensive subjects. Conclusions— These findings indicate that although metabolic abnormalities and elevated heart rate were consistent over time in both hypertensive groups, a lower body mass index and more favorable dietary fat composition predicted the development of white-coat as opposed to sustained hypertension over 20 years.
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| 47. |
- Borenäs, Marcus, et al.
(författare)
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ALK ligand ALKAL2 potentiates MYCN-driven neuroblastoma in the absence of ALK mutation
- 2021
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Ingår i: EMBO Journal. - : John Wiley & Sons. - 0261-4189 .- 1460-2075. ; 40:3
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Tidskriftsartikel (refereegranskat)abstract
- High‐risk neuroblastoma (NB) is responsible for a disproportionate number of childhood deaths due to cancer. One indicator of high‐risk NB is amplification of the neural MYC (MYCN) oncogene, which is currently therapeutically intractable. Identification of anaplastic lymphoma kinase (ALK) as an NB oncogene raised the possibility of using ALK tyrosine kinase inhibitors (TKIs) in treatment of patients with activating ALK mutations. 8–10% of primary NB patients are ALK‐positive, a figure that increases in the relapsed population. ALK is activated by the ALKAL2 ligand located on chromosome 2p, along with ALK and MYCN, in the “2p‐gain” region associated with NB. Dysregulation of ALK ligand in NB has not been addressed, although one of the first oncogenes described was v‐sis that shares > 90% homology with PDGF. Therefore, we tested whether ALKAL2 ligand could potentiate NB progression in the absence of ALK mutation. We show that ALKAL2 overexpression in mice drives ALK TKI‐sensitive NB in the absence of ALK mutation, suggesting that additional NB patients, such as those exhibiting 2p‐gain, may benefit from ALK TKI‐based therapeutic intervention.
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| 48. |
- Borenäs, Marcus, et al.
(författare)
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ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition
- 2024
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490. ; 121:1
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Tidskriftsartikel (refereegranskat)abstract
- High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress in cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia and Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such a strategy in two independent genetically modified mouse NB models. Here, we identify an underlying molecular mechanism, in which ALK signaling leads to phosphorylation of ATR and CHK1, supporting an effective DNA damage response. The importance of ALK inhibition is supported by mouse data, in which ATRi monotreatment resulted in a robust initial response, but subsequent relapse, in contrast to a 14-d ALKi/ATRi combination treatment that resulted in a robust and sustained response. Finally, we show that the remarkable response to the 14-d combined ATR/ALK inhibition protocol reflects a robust differentiation response, reprogramming tumor cells to a neuronal/Schwann cell lineage identity. Our results identify an ability of ATR inhibition to promote NB differentiation and underscore the importance of further exploring combined ALK/ATR inhibition in NB, particularly in high-risk patient groups with oncogene-induced replication stress.
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| 49. |
- Brahme, Anders, et al.
(författare)
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A systems biology approach to radiation therapy optimization
- 2010
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Ingår i: Radiation and Environmental Biophysics. - : Springer Science and Business Media LLC. - 0301-634X .- 1432-2099. ; 49:2, s. 111-124
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Tidskriftsartikel (refereegranskat)abstract
- During the last 20 years, the field of cellular and not least molecular radiation biology has been developed substantially and can today describe the response of heterogeneous tumors and organized normal tissues to radiation therapy quite well. An increased understanding of the sub-cellular and molecular response is leading to a more general systems biological approach to radiation therapy and treatment optimization. It is interesting that most of the characteristics of the tissue infrastructure, such as the vascular system and the degree of hypoxia, have to be considered to get an accurate description of tumor and normal tissue responses to ionizing radiation. In the limited space available, only a brief description of some of the most important concepts and processes is possible, starting from the key functional genomics pathways of the cell that are not only responsible for tumor development but also responsible for the response of the cells to radiation therapy. The key mechanisms for cellular damage and damage repair are described. It is further more discussed how these processes can be brought to inactivate the tumor without severely damaging surrounding normal tissues using suitable radiation modalities like intensity-modulated radiation therapy (IMRT) or light ions. The use of such methods may lead to a truly scientific approach to radiation therapy optimization, particularly when invivo predictive assays of radiation responsiveness becomes clinically available at a larger scale. Brief examples of the efficiency of IMRT are also given showing how sensitive normal tissues can be spared at the same time as highly curative doses are delivered to a tumor that is often radiation resistant and located near organs at risk. This new approach maximizes the probability to eradicate the tumor, while at the same time, adverse reactions in sensitive normal tissues are as far as possible minimized using IMRT with photons and light ions.
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| 50. |
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