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1.
  • Björkman, Kristoffer, et al. (författare)
  • Genotype-phenotype correlations in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1
  • 2014
  • Ingår i: Euromit 2014, 15-19 juni, Tampere, Finland.
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Objectives: To study genotype-phenotype correlations in genes encoding complex I electron input module subunits. Materials and methods: We studied five patients with isolated complex I deficiency, three with NDUFS1 mutations and two with NDUFV1 mutations. A literature review of all reported cases of mutations in the affected genes was performed. Results: The literature review revealed pathological mutations in NDUFS1 for 18 patients in 17 families and correspondingly in NDUFV1 for 26 patients in 19 families. Unpublished clinical data for our five patients were added. Our study showed quite variable clinical courses; death before two years of age was seen in 41% of patients while 18% were alive at seven years. There was a significant difference between the NDUFS1 and NDUFV1 groups for clinical onset and life-span. Mutations in NDUFS1 were linked to a worse clinical course with earlier onset and earlier death. Conclusions: Genotype-phenotype correlations in patients with mutations affecting the genes that encode the electron input module of complex I vary, but patients with NDUFS1 mutation tend to have a worse clinical course than patients with NDUFV1 mutation. Identifying the mutations is of importance for accurate prognostic information and genetic counseling.
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2.
  • Sjöholm, H, et al. (författare)
  • Necrosis of malignant gliomas after intratumoral injection of 201Tl in vivo in the rat
  • 1995
  • Ingår i: Anti-Cancer Drugs. - Rapid Communications. - 0959-4973. ; 6:1, s. 109-114
  • Tidskriftsartikel (refereegranskat)abstract
    • Fourteen adult Fischer 344 rats were inoculated in vivo unilaterally in the caudate nucleus in the brain with malignant RG 2 glioma cells. By 3 weeks a tumor with a diameter of 3-6 mm normally develops. Ten animals which survived the repeated periods of anesthesia and thallium (Tl) injections (intratumorally three times of 201Tl, 15-23 days after inoculation) showed a prolonged retention of radioactivity at the site of injection with no uptake in other organs except for the kidneys. Singular circumscribed necroses were found post-mortem at the site of injection, comprising malignant glioma tumor tissue, which in six animals was absent, in three animals was markedly reduced in size compared with controls and in one animal had the expected size. In four animals metastases were found in distant locations in the brain; in three of these cases there was a retention of radioactivity in the tumor. The selective necrotizing effect on the tumor cells is interpreted as mainly due to emission of Auger electrons from intracellularly accumulated 201Tl, giving rise to very high energy deposition in the vicinity of the cell nucleus. The results should also have implications for the treatment of human malignant gliomas.
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3.
  • Schöll, Michael, 1980-, et al. (författare)
  • Biomarkers for tau pathology.
  • 2019
  • Ingår i: Molecular and cellular neurosciences. - 1095-9327. ; 97, s. 18-33
  • Forskningsöversikt (refereegranskat)abstract
    • The aggregation of fibrils of hyperphosphorylated and C-terminally truncated microtubule-associated tau protein characterizes 80% of all dementia disorders, the most common neurodegenerative disorders. These so-called tauopathies are hitherto not curable and their diagnosis, especially at early disease stages, has traditionally proven difficult. A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions. Tau proteins have also been measured in blood, but the importance of tau-related changes in blood is still unclear. The recent addition of positron emission tomography ligands to visualize, map and quantify tau pathology has further contributed with information about the temporal and spatial characteristics of tau accumulation in the living brain. Together, the measurement of tau with fluid biomarkers and positron emission tomography constitutes the basis for a highly active field of research. This review describes the current state of biomarkers for tau biomarkers derived from neuroimaging and from the analysis of bodily fluids and their roles in the detection, diagnosis and prognosis of tau-associated neurodegenerative disorders, as well as their associations with neuropathological findings, and aims to provide a perspective on how these biomarkers might be employed prospectively in research and clinical settings.
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5.
  • Lundberg, Peter, et al. (författare)
  • Kvantifiering av leversteatos: diagnostisk utvärdering av protonmagnetresonansspektroskopi jämfört med histologiska metoder
  • 2016
  • Konferensbidrag (refereegranskat)abstract
    • <p>Bakgrund</p><p>Leversteatos är den vanligaste manifestationen av leversjukdom i västvärlden. Leverbiopsi med semikvantitativ histologisk gradering är referensmetod vid gradering av leversteatos. Med protonmagnetsresonansspektroskopi (1H-MRS), en metod som föreslagits ersätta leverbiopsi för värdering av steatos, kan leverns innehåll av triglycerider mätas icke-invasivt. Triglyceridinnehåll &gt;5,00 % används ofta som ett diagnostiskt kriterium för leversteatos vid undersökning med 1H-MRS. Syftet med studien var att jämföra 1H-MRS med semikvantitativ histologisk steatosgradering och kvantitativ histologisk steatosmätning.</p><p>Metod</p><p>Patienter remitterade för utredning av förhöjda leverenzymer in-kluderades i studien. Samtliga patienter genomgick klinisk undersökning, laboratorieprovtagning samt 1H-MRS direkt följd av leverbiopsi. För konventionell histologisk semikvantitativ gradering av steatos användes kriterierna utarbetade av Brunt och medarbetare. Kvantitativ mätning av fett i biopsierna utfördes genom att med hjälp av stereologisk punkträkning (SPC) mäta andelen av ytan som innehöll fettvakuoler.</p><p>Resultat</p><p>I studien inkluderades 94 patienter, varav 37 hade icke-alkoholor-sakad fettleversjukdom (NAFLD), 49 hade andra leversjukdomar och 8 hade normal leverbiopsi. En stark korrelation noterades mel-lan 1H-MRS och SPC (r=0,92, p&lt;0,0001; к=0.82). Korrelationen mellan 1H-MRS och Brunts kriterier (к=0.26) samt mellan SPC och Brunts kriterier (к=0.38) var betydligt sämre. När patologens gradering (Brunts kriterier) användes som referensmetod för diag-nos av leversteatos så hade alla patienter med triglyceridinnehåll &gt;5,00 % mätt med 1H-MRS steatos (specificitet 100 %). Emellertid hade 22 av 69 patienter med triglyceridinnehåll ≤5,00 % också le-versteatos enligt Brunts kriterier (sensitivitet 53 %). Motsvarande siffror när man använde gränsvärdet 3,02 % var sensitivitet 79 % och specificitet 100 %. Vid ytterligare reduktion av gränsvärdet för triglyceridinnehåll till 2,00 % ökade sensitiviteten till 87 % med upprätthållande av hög specificitet (94 %).</p><p>Slutsats</p><p>1H-MRS och SPC uppvisade en mycket hög korrelation vid kvantifiering av leversteatos. SPC borde därför föredras framför Brunts kriterier när noggrann histologisk kvantifiering av leversteatos är önskvärd. Många patienter kan ha histologisk leversteatos trots triglyceridinnehåll ≤5,00 % mätt med 1H-MRS. Gränsvärdet för diagnostisering av leversteatos med 1H-MRS bör därför reduceras.</p>
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7.
  • Nilsson, Christer, et al. (författare)
  • Tracking the neurodegeneration of parkinsonian disorders - A pilot study
  • 2007
  • Ingår i: Neuroradiology. - Springer. - 1432-1920. ; 49:2, s. 111-119
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the study was to explore the possibilities of using diffusion tensor imaging (DTI) and tractography (DTT) for the differential diagnosis and monitoring of disease progression in idiopathic Parkinson's disease (IPD), compared with the atypical parkinsonian disorders multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). A 3.0-T MR scanner was used. DTI was acquired using a single-shot EPI sequence with diffusion encoding in 32 directions and a voxel size of 2×2×2 mm3. DTI data were analysed and DTT was performed using the PRIDE fibre tracking tool supplied by the manufacturer. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) within each tract were determined. DTI and DTT images in patients with moderate to advanced MSA demonstrated degeneration of the middle cerebellar peduncles and pontine crossing tracts, with decreased FA and increased ADC. This accounted for most of the pontine and cerebellar atrophy characteristic of this disease. In contrast, patients with PSP showed a selective degeneration of the superior cerebellar peduncle. Three-dimensional images of whole-brain white matter tracts demonstrated a reduction of cortical projection fibres in all patients with PSP. Visualization of the selective degeneration of individual fibre tracts, using DTI and DTT, adds qualitative data facilitating the differential diagnosis of parkinsonian disorders. Repeated measurements of FA and ADC values in a whole fibre tract might be used for monitoring disease progression and studying the effect of treatment in neuroprotective trials. The results are preliminary considering the small number of subjects in the study. © Springer-Verlag 2007.
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9.
  • Matson, Sophia, et al. (författare)
  • Nonattendance in mammographic screening: a study of intraurban differences in Malmo, Sweden, 1990-1994
  • 2001
  • Ingår i: Cancer Detection and Prevention. - Elsevier. - 0361-090X. ; 25:2, s. 132-137
  • Tidskriftsartikel (refereegranskat)abstract
    • Mammographic screening may reduce breast cancer mortality. Not all women, however, come for examination. The objective in this study from Malmo has been to assess extent to which the rate of nonattendance varies between residential areas with different sociodemographic profiles. The study is based on 32,605 women, 45 to 68 years old and living in 17 areas, who between 1990 and 1994 were invited to screening. Between age groups, the age-specific nonattendance rate ranged from 31% to 35 % (P < .01). The nonattendance rate was highest for women 65 years or older. Between residential areas, age-adjusted nonattendance rates ranged from 23% to 43% (P < .01). A socioeconomic score was developed to express the socioeconomic circumstances in the residential areas and ranged from -7.18 in the most deprived area to 5.01 in the least. Nonattendance covaried in an inverse fashion with the socioeconomic score (r = -0.78; P < .01). One of three women in this urban population did not accept the invitation to mammographic screening. Our conclusion is that women in areas with less favorable circumstances seem to be less willing to participate.
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10.
  • Ramgren, B, et al. (författare)
  • Vertebrobasilar dissection with subarachnoid hemorrhage: a retrospective study of 29 patients.
  • 2005
  • Ingår i: Neuroradiology. - Springer. - 1432-1920. ; 47:2, s. 97-104
  • Tidskriftsartikel (refereegranskat)abstract
    • We have reviewed initial diagnostic features, treatment, and outcome in 29 patients with acute subarachnoid hemorrhage due to non-traumatic vertebrobasilar artery dissection diagnosed in our hospital between 1993 and 2003. The dissections occurred in the vertebral artery in 19 patients, the posterior inferior cerebellar artery ( PICA) in two patients, the basilar artery in four patients, and in the vertebral artery extending into the PICA in four patients. A pseudoaneurysm was found in 20 patients. Clinical manifestations typically included sudden onset of moderate to severe headache, nuchal rigidity, and drowsiness. Fourteen patients were treated conservatively. Fifteen patients underwent endovascular treatment with either parent artery occlusion ( 13 patients) or aneurysmal coil occlusion with preservation of the parent artery ( 2 patients). Re-bleeding occurred within 12 days and before treatment in nine patients. Eight of these had a pseudoaneurysm. No patient bled after endovascular treatment. Poor grade and early re-bleeding were associated with less favorable outcome. Outcome at 6 months did not differ significantly between endovascular and conservative treatment. Altogether, good recovery was achieved for 16 patients, moderate disability was seen in one, severe disability in four, and eight patients ( 27%) died. The absence of bleeding subsequent to endovascular treatment in this study suggests that endovascular treatment may be a rational approach in these patients at high risk of re-bleeding, especially those with a pseudoaneurysm.
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