| 1. |
- Areblom, Maria, et al.
(författare)
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A Description of the Yield of Genetic Reinvestigation in Patients with Inherited Retinal Dystrophies and Previous Inconclusive Genetic Testing
- 2023
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Ingår i: Genes. - 2073-4425. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- In the present era of evolving gene-based therapies for inherited retinal dystrophies (IRDs), it has become increasingly important to verify the genotype in every case, to identify all subjects eligible for treatment. Moreover, combined insight concerning phenotypes and genotypes is crucial for improved understanding of thevisual impairment, prognosis, and inheritance. The objective of this study was to investigate to what extent renewed comprehensive genetic testing of patients diagnosed with IRD but with previously inconclusive DNA test results can verify the genotype, if confirmation of the genotype has an impact on the understanding of the clinical picture, and, to describe the genetic spectrum encountered in a Swedish IRD cohort. The study included 279 patients from the retinitis pigmentosa research registry (comprising diagnosis within the whole IRD spectrum), hosted at the Department of Ophthalmology, Skåne University hospital, Sweden. The phenotypes had already been evaluated with electrophysiology and other clinical tests, e.g., visual acuity, Goldmann perimetry, and fundus imaging at the first visit, sometime between 1988–2015 and the previous—in many cases, multiple—genetic testing, performed between 1995 and 2020 had been inconclusive. All patients were aged 0–25 years at the time of their first visit. Renewed genetic testing was performed using a next generation sequencing (NGS) IRD panel including 322 genes (Blueprint Genetics). Class 5 and 4 variants, according to ACMG guidelines, were considered pathogenic. Of the 279 samples tested, a confirmed genotype was determined in 182 (65%). The cohort was genetically heterogenous, including 65 different genes. The most prevailing were ABCA4 (16.5%), RPGR (6%), CEP290 (6%), and RS1 (5.5%). Other prevalent genes were CACNA1F (3%), PROM1 (3%), CHM (3%), and NYX (3%). In 7% of the patients there was a discrepancy between the diagnosis made based on phenotypical or genotypical findings alone. To conclude, repeated DNA-analysis was beneficial also in previously tested patients and improved our ability to verify the genotype–phenotype association increasing the understanding of how visual impairment manifests, prognosis, and the inheritance pattern. Moreover, repeated testing using a widely available method could identify additional patients eligible for future gene-based therapies.
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| 2. |
- Cardiakidis Myers, Anna, et al.
(författare)
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Rifabutin accumulates in the lens and reduces retinal function in the rabbit eye
- 2009
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Ingår i: Retina. - 0275-004X. ; 29:1, s. 106-111
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study the toxicology of rifabutin in the rabbit eye with emphasis on retinal function and histopathology.METHODS: Seven rabbits received a daily dose of rifabutin during 15 months. Six rabbits receiving only the vehicle were used as controls. Repeated standardized full-field electroretinograms (ERG) were assessed. After discontinuing treatment, the rabbits were killed and the cornea, the lens, and the sectioned retina was studied. Immunhistochemistry directed against vimentin, glial fibrillaryacidic protein (GFAP), protein kinase C (PKC), and peanut agglutinin (PNA) was performed.RESULTS: Rifabutin was detected in serum of the treated rabbits. During treatment, the full-field ERG demonstrated significantly reduced b-wave amplitudes in the total rod-cone response as well as in the isolated rod and cone response compared with the recordings before treatment. The control rabbits did not demonstrate a reduction of the ERG amplitudes. The treated rabbits developed a discoloration of the lens, not seen in the control group. No retinal pathology was demonstrated using immunohistochemical methods.CONCLUSION: Rifabutin causes a discoloration of the lens and reduces both rod and cone function in rabbits, but does not alter retinal morphology. Previous reports on ocular side effects caused by rifabutin are supported by the results of this study.
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| 3. |
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| 4. |
- Kjellström, Sten, et al.
(författare)
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Long-term 12 year follow-up of X-linked congenital retinoschisis.
- 2010
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Ingår i: Ophthalmic Genetics. - : Informa UK Limited. - 1744-5094 .- 1381-6810. ; Jul 1, s. 114-125
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the retinal structure and function during the progression of X-linked retinoschisis (XLRS) from childhood to adulthood. Methods: Ten patients clinically diagnosed with XLRS were investigated at 6-15 years of age (mean age 9 years) with a follow-up 8 to 14 years later (mean 12 years). The patients underwent regular ophthalmic examination as well as testing of best corrected visual acuity (BCVA), visual field (VF) and assessment of full-field electroretinography (ERG) during their first visit. During the follow-up, the same clinical protocols were repeated. In addition, macular structure and function was examined with multifocal electroretinography (mfERG) and optical coherence tomography (OCT). The patients were 18-25 years of age (mean age 21 years) at the follow-up examination. All exons and exon-intron boundaries of RS1-gene were sequenced for gene mutations in 9 out of the 10 patients. Results: Best corrected VA and VF were stable during this follow-up period. No significant progression in cone or rod function could be measured by full-field ERG. Multifocal electroretinography and OCT demonstrated a wide heterogeneity of macular changes in retinal structure and function at the time of follow-up visit. Three different mutations were detected in these nine patients, including a known nonsense mutation in exon 3, a novel insertion in exon 5 and an intronic mutation at 5' splice site of intron 3. Conclusions: Clinical follow-up (mean 12 years) of ten young XLRS patients (mean age of 9 years) with a typical congenital retinoschisis phenotype revealed no significant decline in retinal function during this time period. MfERG and OCT demonstrated a wide variety of macular changes including structure and dysfunction. The XLRS disease was relatively stable during this period of observation and would afford opportunity for therapy studies to judge benefit against baseline and against the fellow eye.
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| 5. |
- Kjellström, Sten, et al.
(författare)
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Retinal function and histopathology in rabbits treated with Topiramate.
- 2006
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Ingår i: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 1573-2622 .- 0012-4486. ; 113:3, s. 179-186
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To evaluate retinal function and histopathology in rabbits treated orally with the antiepileptic drug topiramate. Methods Six rabbits were treated with a daily oral dose of topiramate during a period of eight months. Six rabbits receiving water served as controls. Blood samples were analyzed for determination of topiramate serum levels in order to ensure successful drug exposition. Standardized full-field electroretinograms (ERGs) were performed before treatment and then at 2, 3 and 8 months during the treatment period. After terminating treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied. Results After eight months of treatment the fullfield ERG demonstrated normal rod function in treated and control rabbits, but the light adapted 30 Hz flicker b-wave amplitude was significantly reduced in the treated rabbits. This was the case for both the light adapted (Wilcoxon signed ranks test, P=0.046) and the dark adapted (Wilcoxon signed ranks test, P=0.028) 30 Hz flicker response from the treated rabbits. Retinal immunohistology revealed a severe accumulation of GABA in amacrine cells and in the inner plexiform layer in 4 of 6 treated rabbits compared to the controls. Conclusions Topiramate, orally administrated to rabbits, may cause a significant reduction of the retinal function demonstrated by the reduced b-wave amplitude in the full-field ERG, as well as changes in immunohistology characterized by a severe accumulation of GABA in the inner retina. The retinal dysfunction and the morphological changes indicate that topiramat may damage the retina, similarly to vigabatrin (another antiepileptic drug).
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| 6. |
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| 7. |
- Ponjavic, Vesna, et al.
(författare)
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Alterations in electroretinograms and retinal morphology in rabbits treated with vigabatrin
- 2004
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Ingår i: Documenta Ophthalmologica. - 1573-2622. ; 108:2, s. 125-133
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine whether long-term treatment with the anti-epileptic drug vigabatrin causes damage to rabbit retina.METHODS: Five rabbits were treated continuously with a daily dose of vigabatrin solution per orally during a period of 1-8 months. Two rabbits receiving water were used as controls. Repeated full-field electroretinograms (every two weeks) were assessed during this period. Vigabatrin serum concentration was repeatedly measured for securing successful drug administration. After termination of treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied.RESULTS: In all rabbits treated with vigabatrin the serum analyses repeatedly demonstrated elevated drug concentration. Full-field electroretinograms demonstrated normal rod function in all treated rabbits, but reduced cone function in two of the five treated rabbits verified by 30Hz flicker stimulation. Morphologic studies of the sectioned retina demonstrated GFAP immunoactivity of the glial cells localized in the retinal periphery in all five treated rabbits, one of which had staining also in the centrally localized glial cells. The treated rabbits also demonstrated a weaker GAD staining in the IPL and less positive amacrine cells, compared to the controls. Only two treated rabbits had normal GABA staining while three had an enhanced GABA immunoreactivity and undistinguishable fibers in the IPL. In three out of five treated rabbits the Müller cells were short, stubby and fragmented, with swollen endfeet.CONCLUSION: This study demonstrates changes in histopathology caused by vigabatrin in an animal model, which has not been reported previously. We have found that vigabatrin orally administrated to rabbits does not affect rod function but may reduce cone function in the full-field electroretinogram, which is similar to the previously reported vigabatrin effect on the human ERG. The results indicate that vigabatrin may damage or influence, at least one cell type in the rabbit retina.
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| 8. |
- Abdulridha-Aboud, Wissam, et al.
(författare)
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Characterization of macular structure and function in two swedish families with genetically identified autosomal dominant retinitis pigmentosa
- 2016
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Ingår i: Molecular Vision. - 1090-0535. ; 22, s. 362-373
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the phenotype in two families with genetically identified autosomal dominant retinitis pigmentosa (adRP) focusing on macular structure and function. Methods: Clinical data were collected at the Department of Ophthalmology, Lund University, Sweden, for affected and unaffected family members from two pedigrees with adRP. Examinations included optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Molecular genetic screening was performed for known mutations associated with adRP. Results: The mode of inheritance was autosomal dominant in both families. The members of the family with a mutation in the PRPF31 (p.IVS6+1G>T) gene had clinical features characteristic of RP, with severely reduced retinal rod and cone function. The degree of deterioration correlated well with increasing age. The mfERG showed only centrally preserved macular function that correlated well with retinal thinning on OCT. The family with a mutation in the RHO (p.R135W) gene had an extreme intrafamilial variability of the phenotype, with more severe disease in the younger generations. OCT showed pathology, but the degree of morphological changes was not correlated with age or with the mfERG results. The mother, with a de novo mutation in the RHO (p.R135W) gene, had a normal ffERG, and her retinal degeneration was detected merely with the reduced mfERG. Conclusions: These two families demonstrate the extreme inter-and intrafamilial variability in the clinical phenotype of adRP. This is the first Swedish report of the clinical phenotype associated with a mutation in the PRPF31 (p.IVS6+1G>T) gene. Our results indicate that methods for assessment of the central retinal structure and function may improve the detection and characterization of the RP phenotype.
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| 9. |
- Acar, C, et al.
(författare)
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Mutation screening of patients with Leber congenital amaurosis or the enhanced S-cone syndrome reveals a lack of sequence variations in the NRL gene
- 2003
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Ingår i: Molecular Vision. - 1090-0535. ; 9:3-4, s. 14-17
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine if mutations in the retinal transcription factor gene NRL are associated with retinopathies other than autosomal dominant retinitis pigmentosa (adRP). Methods: Genomic DNA was isolated from blood samples obtained from 50 patients with Leber Congenital Amaurosis (LCA), 17 patients with the Enhanced S-Cone Syndrome (ESCS), and a patient with an atypical retinal degeneration that causes photoreceptor rosettes with blue cone opsin. The 5' upstream region (putative promoter), untranslated exon 1, coding exons 2 and 3, and exon-intron boundaries of the NRL gene were analyzed by direct sequencing of the PCR-amplified products. Results: Complete sequencing of the NRL gene in DNA samples from this cohort of patients revealed only one nucleotide change. The C->G transversion at nucleotide 711 of NRL exon 3 was detected in one LCA patient; however, this change did not alter the amino acid (L237L). Conclusions: No potential disease causing mutation was identified in the NRL gene in patients with LCA, ESCS, or the atypical retinal degeneration. Together with previous studies, our results demonstrate that mutations in the NRL gene are not a major cause of retinopathy. To date, only missense changes have been reported in adRP patients, and sequence variations are rare. It is possible that the loss of NRL function in humans is associated with a more complex clinical phenotype due to its expression in pineal gland in addition to rod photoreceptors.
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| 10. |
- Andreasson, Jakob, 1975, et al.
(författare)
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Electron-lattice interactions in the perovskite LaFe0.5Cr0.5O3 characterized by optical spectroscopy and LDA plus U calculations
- 2009
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X .- 2469-9950 .- 2469-9969. ; 80:7, s. 075103-
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Tidskriftsartikel (refereegranskat)abstract
- We use resonance Raman scattering (incident photon energies between 1.8 and 4.13 eV), LDA+U calculations, spectroscopic ellipsometry, and oblique IR reflectivity to characterize the strong electron-phonon interactions in the disordered perovskite LaFe0.5Cr0.5O3. When the photon energy coincides with a Cr to Fe Mott-Hubbard transfer gap around 2.4 eV the electron-phonon interaction is manifested by a Franck-Condon effect with exceptional first-and higher order scattering of a local oxygen breathing mode. At higher incident energies we observe a superposition of Franck-Condon scattering and Frohlich interaction induced infrared active longitudinal optical two-phonon scattering activated mainly by O to Fe charge transfer. Our results establish LaFe0.5Cr0.5O3 as a model compound for research on electron-phonon interactions in strongly correlated complex systems and show that Franck-Condon scattering in complex solids is not limited to Jahn-Teller active compounds.
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| 11. |
- Andreasson, Jakob, 1975, et al.
(författare)
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Electron-phonon interactions in perovskites containing Fe and Cr studied by Raman scattering using oxygen-isotope and cation substitution
- 2008
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X .- 2469-9950 .- 2469-9969. ; 78:23, s. 235103-
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Tidskriftsartikel (refereegranskat)abstract
- We use temperature-dependent inelastic light scattering to study the origin of the strong multiphonon scattering of a local oxygen breathing mode present in the mixed B-site orthorhombic (space group Pnma) perovskite LaFe0.5Cr0.5O3 but absent in isostructural LaFeO3 and LaCrO3. It is seen that the multiphonon scattering is critically sensitive to the presence of both Fe and Cr ions on the B site. These results support our interpretation that the multiphonon scattering is activated by local electron-phonon interactions according to the Franck-Condon picture following an Fe-Cr charge transfer. Further, O-18 substitution is performed on the x=0, 0.04, and 0.5 compounds and clearly shows that all modes appearing above the first-order phonon-scattering region in these compounds originate from higher-order oxygen stretching vibrations. In particular this is the case for the strong second-order scattering dominating the scattering response in LaFeO3. Accordingly we propose that these modes are generated by infrared-active longitudinal optical (IR LO) two-phonon and combination scattering activated by Frohlich interaction. For x=0.02 and 0.04 the characteristic IR LO two-phonon and Franck-Condon multiphonon-scattering profiles mix. We also study the influence of isovalent cation substitution and Sr doping in AFe(0.5)Cr(0.5)O(3) (A=La, Nd, and Gd) and La1-ySryFe0.5Cr0.5O3-delta (y=0, 0.16, and 0.5) on the strong electron-phonon coupling present in LaFe0.5Cr0.5O3. The Franck-Condon effect in LaFe0.5Cr0.5O3, is not significantly affected by isovalent A-site substitution, despite the increasing orthorhombic distortion associated with decreasing A-site ionic radii. On the contrary, aliovalent Sr doping causes a rapid decrease in the Franck-Condon scattering. This shows that the strong electron-phonon coupling in these compounds is highly sensitive to local lattice and electronic decoherence but insensitive to global lattice distortions. Finally, a preliminary assignment of the A(g) and B-2g phonon modes in AFe(0.5)Cr(0.5)O(3) (A=La, Nd, and Gd) is made based on the present observations and published results for LaCrO3 and AMnO(3). The modes associated with oxygen octahedral tilt and bending vibrations are heavily influenced by the magnitude of the orthorhombic distortion.
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| 12. |
- Andreasson, Jakob, 1975, et al.
(författare)
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Franck-Condon higher order lattice excitations in the LaFe(1-x)Cr(x)O3 (x=0, 0.1, 0.5, 0.9, 1.0) perovskites due to Fe-Cr charge transfer effects
- 2007
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Ingår i: Physical Review B. ; 75, s. 104302-
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Tidskriftsartikel (refereegranskat)abstract
- First and higher order lattice excitiations in the B-site disordered perovskites LaFe(1-x)Cr(x)O3 (x = 0, 0.1, 0.5, 0.9, 1) and La(0.835)Sr(0.165)Fe(0.5)Cr(0.5)O(3-d) are investigated using temperature dependent and polarised inelastic light scattering [lambda = 515 nm (2.41 eV) and 676 nm (1.83 eV)] on oriented crystallites.A peak at approximately 2.4 eV in the imaginary part of the dielectric function of LaFe(0.5)Cr(0.5)O3 is assigned to a charge transfer from Fe 3+ (d5) to Cr 3+ (d3) ions and coupled the appearance of an intense Ag-like mode at approximately 700 cm-1 in the Raman data. This excitation is identified as a symmetric oxygen breathing mode activated by the Fe-Cr charge transfer through an orbital coupling mechanism. Higher order scattering (up to 7th order) of the intrinsic Raman active symmetric breathing mode is also explained by an orbital mediated, electron-phonon coupling, similar to the Franck-Condon effect observed in the Jahn-Teller active perovskite structured manganite LaMnO3. These results show that the Franck-Condon mechanism is a more common mechanism for resonant higher order scattering in solids than previously believed and propose the LaFe(1-x)Cr(x)O(3) system as a model system for electron-phonon coupling and higher order Raman scattering in solids.
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| 13. |
- Andreasson, Jakob, et al.
(författare)
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Franck-Condon higher order lattice excitations in the LaFe1-xCrxO3 (x=0, 0.1, 0.5, 0.9, 1.0) perovskites due to Fe-Cr charge transfer effects
- 2007
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 75
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Tidskriftsartikel (refereegranskat)abstract
- First and higher order lattice excitations in the B-site disordered perovskites LaFe1-xCrxO3 (x=0, 0.1, 0.5, 0.9, and 1) and La0.835Sr0.165Fe0.5Cr0.5O3-delta are investigated using temperature dependent and polarized inelastic light scattering [lambda=515 nm (2.41 eV) and 676 nm (1.83 eV)] on oriented crystallites. A peak at approximately 2.4 eV in the imaginary part of the dielectric function of LaFe0.5Cr0.5O3 is assigned to a charge transfer from Fe3+ (d(5)) to Cr3+ (d(3)) ions, coupled with the appearance of an intense A(g)-like mode at approximately 700 cm(-1) in the Raman data. This excitation is identified as a symmetric oxygen breathing mode activated by the Fe-Cr charge transfer through an orbital coupling mechanism. Higher order scattering (up to seventh order) of the intrinsic Raman active symmetric breathing mode is also explained by an orbital-mediated electron-phonon coupling, similar to the Franck-Condon effect observed in the Jahn-Teller active-perovskite-structured manganite LaMaO(3). These results show that the Franck-Condon mechanism is a more common mechanism for resonant higher order scattering in solids than previously believed and propose the LaFe1-xCrxO3 system as a model system for electron-phonon coupling and higher order Raman scattering in solids.
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| 14. |
- Andreasson, Kristin I. M., 1963, et al.
(författare)
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Biological weighting functions as a tool for evaluating two ways to measure UVB radiation inhibition on photosynthesis
- 2006
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Ingår i: Journal of Photochemistry and Photobiology B-Biology. - : Elsevier BV. - 1011-1344. ; 84:2, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- To estimate the inhibitory effect of the changing UVB radiation (UVBR, 280-315 nm) on earth's ecosystems, an understanding of its wavelength dependency is needed. The tool used for these estimations is the biological weighting function (BWF), whereby the inhibition of different wavelengths is calculated. B\WFs were determined for three algae species from different classes, Phaeodactylum tricornutum (Bacillariophyceae), Dunaliella tertiolecta (Chlorophyceae) and Rhodomonas sp. (Cryptophyceae), using polychromatic irradiation, where the UVBR spectra were varied with cut-off filters. For each alga, BWFs were determined for two photosynthetic parameters; the quantum yield measured as fluorescence from Photo System II in a pulse-amplitude-modulation (PAM) fluorometer, and the fixation of C-14-labelled carbon dioxide. The BWFs were calculated with the Rundel method, using the radiation data between 270 and 360 nm with 1 nm resolution. The results show that the UVBR damages were generally higher when using the carbon fixation measurements than when measuring with the PAM technique. When using PAM, P. tricornutum in particular had a sensitivity intermediate between the sensitive Rhodomonas sp. and the more tolerant D. tertiolecta, but was as sensitive as, or even more sensitive, than Rhodomonas sp. when using carbon fixation. D. tertiolecta was shown to be less sensitive when using both techniques and the inhibition of its photosynthesis was almost as high when using PAM as when using carbon fixation. We concluded that, although the PAM technique has advantages such as being cleaner and easier to use, it is unable to Substitute the carbon fixation measurements. Not only are the algae less sensitive when measured with PAM than they are when measured as carbon fixation, the relationship between the effects on the algae measured with the two techniques also differs. As fixation of carbon dioxide integrates a larger part of the photosynthetic machinery, it should be favoured as a measure of photosynthesis. (c) 2006 Elsevier B.V. All rights reserved.
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| 15. |
- Andreasson, Kristin I. M., 1963, et al.
(författare)
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Reduction in growth rate in Phaeodactylum tricornutum (Bacillarlophyceae) and Dunaliella tertiolecta (Chlorophyceae) induced by UV-B radiation
- 2007
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Ingår i: Journal of Photochemistry and Photobiology B-Biology. - : Elsevier BV. - 1011-1344. ; 86:3, s. 227-233
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Tidskriftsartikel (refereegranskat)abstract
- The effect of UV-B radiation (UVBR, 280-315 nm) on growth rate during 72 h of incubation, was measured for two marine microalgae - Dunaliella tertiolecta (Chlorophyceae) and Phaeodactyhan tricornutum (Bacillariophyceae). The resulting inhibition of growth rate was analysed by calculating biological weighting functions (BWFs). The growth rate of D. tertiolecta was slightly more inhibited by UVBR (over the whole range of the spectrum) than was the growth rate of P. tricornutum, but the wavelength dependencies were the same. Our results were compared with results from photosynthesis experiments of Andreasson and Wangberg [1], where two methods, pulse amplitude modulation (PAM) fluorescence and carbon fixation, were measured for these same algae. The BWF for the growth rate, here, showed more wavelength dependency than the BWF for the previous two photosynthesis measurements - except for the carbon fixation BWF in P. tricornutum, which was closer to the BWF for growth rate. The wavelength dependency of the growth rate inhibition showed less variation between the species than the inhibition of the photosynthesis. (c) 2006 Elsevier B.V. All rights reserved.
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| 16. |
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| 17. |
- Andréasson, Sven, et al.
(författare)
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Behandling av alkohol- och narkotikaproblem : En evidensbaserad kunskapssammanställning
- 2001
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Utvärderingens syfteMissbruk och beroende av alkohol är ett av de största folkhälsoproblemen. Narkotikamissbruk är mindre vanligt men har stora medicinska konsekvenser för de berörda. De sociala och juridiska aspekterna är betydande. En kritisk genomgång av litteraturen vad avser behandling av abstinens, protraherad abstinens, behandling i syfte att förhindra återfall, psykologiska och sociala behandlingar för att minska återfallsrisken, behandlingsprogram och institutionsvårdens roll, samt behandling av missbruk under graviditet. Dessutom en granskning av mini-intervention i primärvård och annan vård vars syfte är att minska konsumtionen hos högkonsumenter av alkohol. Nyligen gjorda meta-analyser inom området värderas och särskild vikt fästs vid interventioner som finns eller lätt kan introduceras i den svenska vårdorganisationen. Behandlingsprogram för patienter med samtidig annan psykisk störning värderas.Så kallat lågdosberoende av bensodiazepiner och andra lugnande medel eller sömnmedel behandlas inte. Inte heller belyses effekten av behandlingar vars primära mål är kroppsliga komplikationer av missbruket, och inte heller granskas metoder att minska tillgänglighet.TillvägagångssättStrukturerad översikt, kostnadsanalyser.Insamling av primärdataSystematisk sökning i relevanta databaser, litteraturlistor i påträffade studier samt i aktuella monografier. Ingen bakre tidsbegränsning och sökning i databaser till och med februari 1999.Utgångspunkt för urval av dataHuvudsakligen randomiserade, kontrollerade, dubbelblinda studier, samt metaanalyser som baseras på sådana studier. Vad gäller långtidsförlopp och ekonomiska analyser även kohortstudier och andra naturalistiska studier.Genomgång av publikationenSamtliga studier värderas med hjälp av en i gruppen utarbetad, och med övriga psykiatriprojekt gemensam, kvalitetsmall. Alla centrala studier läses av minst två i gruppen.Färdiga manuskript värderas av styrelse, expertgrupp samt externa granskare.
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| 18. |
- Andréasson, Sten, et al.
(författare)
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Clinical studies of X-linked retinitis pigmentosa in three Swedish families with newly identified mutations in the RP2 and RPGR-ORF15 genes
- 2003
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Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1381-6810 .- 1744-5094. ; 24:4, s. 215-223
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe new disease-causing RP2 and RPGR-ORF15 mutations and their corresponding clinical phenotypes in Swedish families with X-linked retinitis pigmentosa (XLRP) and to establish genotype-phenotype correlations by studying the clinical spectrum of disease in families with a known molecular defect. Methods: Seventeen unrelated families with RP and an apparent X-linked pattern of disease inheritance were identified from the Swedish RP registry and screened for mutations in the RP2 and RPGR (for the RP3 disease) genes. These families had been previously screened for the RPGR exons 1-19, and disease-causing mutations were identified in four of them. In the remaining 13 families, we sequenced the RP2 gene and the newly discovered RPGR-ORF exon. Detailed clinical evaluations were then obtained from individuals in the three families with identified mutations. Results: Mutations in RP2 and RPGR-ORF15 were identified in three of the 13 families. Clinical evaluations of affected males and carrier females demonstrated varying degrees of retinal dysfunction and visual handicap, with early onset and severe disease in the families with mutations in the ORF15 exon of the RPGR gene. Conclusions: A total of seven mutations in the RP2 and RPGR genes have been discovered so far in Swedish XLRP families. All affected individuals express a severe form of retinal degeneration with visual handicap early in life, although the degree of retinal dysfunction varies both in hemizygous male patients and in heterozygous carrier females. Retinal disease phenotypes in patients with mutations in the RPGR-ORF15 were more severe than in patients with mutations in RP2 or other regions of the RPGR.
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| 19. |
- Andréasson, Sten, et al.
(författare)
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Cone implicit time as a predictor of visual outcome in macular hole surgery.
- 2014
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Ingår i: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 1435-702X .- 0721-832X. ; 252:12, s. 1903-1909
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether preoperative retinal function measured by full-field ERG and multifocal ERG is correlated to postoperative visual acuity after macular hole surgery.
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| 20. |
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| 21. |
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| 22. |
- Andréasson, Sten, et al.
(författare)
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Phenotypes in three Swedish families with X-linked retinitis pigmentosa caused by different mutations in the RPGR gene
- 1997
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Ingår i: American Journal of Ophthalmology. - 1879-1891. ; 124:1, s. 95-102
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To assess the clinical phenotypes in three Swedish families with X-linked retinitis pigmentosa caused by different mutations in the RPGR gene. METHODS: Three families from different parts of Sweden, including nine patients with retinitis pigmentosa and six female carriers of X-linked retinitis pigmentosa, were examined clinically. Ophthalmologic examination included kinetic perimetry with a Goldmann perimeter using standardized objects I4e and V4e, dark adaptation final thresholds with a Goldmann-Weeker adaptometer, and full-field electroretinograms. RESULTS: The clinical findings in the patients demonstrated a severe form of retinitis pigmentosa with visual handicap early in life. Patients with a microdeletion of exons 8 through 10 of the RPGR gene had a more severe phenotype compared to the patients with single base-pair mutations in the introns 10 and 13 of the RPGR gene, resulting in splicing defects. Furthermore, heterozygous carriers in these families displayed a wide spectrum of clinical features, from minor symptoms to severe visual disability. CONCLUSION: These three families show a variable clinical phenotype resulting from different mutations in the RPGR gene. A microdeletion spanning at least parts of exons 8 through 10 seems to result in a severe phenotype compared to the splice defects. Heterozygous carriers of X-linked retinitis pigmentosa with these specific RPGR genotypes also show a variability of the phenotype; carriers with the microdeletion may be severely visually handicapped.
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| 23. |
- Andréasson, Sten
(författare)
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Treatments for all RP-patients?
- 2010
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Ingår i: Acta Ophthalmologica. - 1755-3768. ; 88, s. 127-127
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Konferensbidrag (refereegranskat)
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| 24. |
- Andreasson, Sten, et al.
(författare)
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Undersökning av kustfisket i Bottniska viken 1991
- 1993
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Fiskeriverkets utredningskontor i Luleå och Härnösand samt kustlaboratoriet i Öregrund har utfört en kartering av kustfisket i Bottniska viken. Fyra områden har studerats under 1991, Gräsö, Hornslandet, Holmön och Råneå skärgård. Områdenas omfattning och lägen framgår av figur 1. Undersökningen ingår som en del i Kustfiskeprojektet och har genomförts i form av en enkätundersökning. Syftet har varit att få en bild av fisket i respektive område; i vilken utsträckning fiske bedrivs, med vilka redskap det fiskas, hur stort fångstuttaget är samt fördelningen mellan fritids- och yrkesfiske. Framförallt har fritidsfisket belysts, eftersom omfattningen och strukturen av detta fiske varit dåligt känd.
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| 25. |
- Arnell, Henrik, et al.
(författare)
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Stargardt disease : linkage to the ABCR gene region on 1p21-p22 in Scandinavian families
- 1998
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 76:6, s. 649-52
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Tidskriftsartikel (refereegranskat)abstract
- Stargardt disease (STGD) or fundus flavimaculatus (FFM) is one of the most frequent causes of macular degeneration in childhood. The disease is inherited as an autosomal recessive trait and the corresponding gene has been localized to chromosome 1p21-22 and subsequently identified as the ATP-binding cassette transporter (ABCR) gene. PURPOSE: To characterize Finnish and Swedish STGD families genetically, with special reference to chromosome region 1p21-22. METHODS: We performed genetic linkage and haplotype analyses in five families of Finnish and Swedish origin with members affected by STGD or FFM. RESULTS: Evidence for linkage between STGD and the ABCR gene region on chromosome 1p was found with a maximum cumulative two-point lod score for marker D1S188 (Z=4.04, theta=0.001). The affected individuals of all families, including the offspring of a consanguineous family, were found heterozygous for haplotypes spanning the ABCR gene. CONCLUSION: The results support genetic homogeneity for a STGD/FFM gene defect on chromosome 1p21-22. A variety of haplotypes tightly linked to the ABCR gene region were found among affected individuals which indicate the presence of several independent STGD mutations in the Scandinavian population.
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| 26. |
- Barth, Henrik, et al.
(författare)
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A cross-linked hyaluronic acid hydrogel (Healaflow(®)) as a novel vitreous substitute
- 2016
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Ingår i: Graefe's Archives for Clinical and Experimental Ophthalmology. - : Springer. - 0721-832X .- 1435-702X. ; 254:4, s. 697-703
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Vitrectomy requires the substitution of the natural vitreous, as well as tamponading of retinal breaks. Clinically available alternatives such as gas and silicone oil have side effects such as inflammation, secondary glaucoma, cataract, and a need for head posturing. In this study, a hydrogel of cross-linked sodium hyaluronic acid (Healaflow(®)) is evaluated for use as a novel vitreous substitute.Methods: A combined 25-20-gauge pars plana vitrectomy with posterior vitreous detachment was performed in the right eye of twelve pigmented rabbits, with subsequent injection of approximately 1 ml Healaflow(®). Clinical evaluation, measurement of intraocular pressure (IOP), and full-field ERG were performed postoperatively. The rabbits were sacrificed at different time-points between 42 and 105 days. After enucleation, the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy and immunohistochemistry.Results: Healaflow(®) was successfully used with standard surgical procedures and remained translucent but did lose most of its viscosity during the postoperative period. One rabbit was lost due to unrelated causes. In two eyes iatrogenic partial retinal detachments were seen, and in two eyes significant cataract developed due to intra-operative complications. ERG-recordings revealed no toxic effect on rod or cone function. Routine microscopy and immunohistochemistry demonstrated normal morphology with some Müller cell activation (up-regulation of glial acidic fibrillary protein, GFAP) compared to unoperated eyes and no significant DNA-fragmentation (TUNEL-assay).Conclusions: Healaflow® did not affect retinal morphology or function negatively during long-term use as a vitreous substitute, making it highly interesting in this setting. An estimated retention time of a few weeks suggests potential for use as a short-term tamponade. Future work will include an increased ratio of cross-linking to prolong the structural integrity of the gel.
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| 27. |
- Bedoni, Nicola, et al.
(författare)
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Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility
- 2016
-
Ingår i: Human Molecular Genetics. - 0964-6906. ; 25:20, s. 4546-4555
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary retinal degenerations encompass a group of genetic diseases characterized by extreme clinical variability. Following next-generation sequencing and autozygome-based screening of patients presenting with a peculiar, recessive form of cone-dominated retinopathy, we identified five homozygous variants [p.(Asp594fs), p.(Gln117*), p.(Met712fs), p.(Ile756Phe), and p.(Glu543Lys)] in the polyglutamylase-encoding gene TTLL5, in eight patients from six families. The two male patients carrying truncating TTLL5 variants also displayed a substantial reduction in sperm motility and infertility, whereas those carrying missense changes were fertile. Defects in this polyglutamylase in humans have recently been associated with cone photoreceptor dystrophy, while mouse models carrying truncating mutations in the same gene also display reduced fertility in male animals. We examined the expression levels of TTLL5 in various human tissues and determined that this gene has multiple viable isoforms, being highly expressed in testis and retina. In addition, antibodies against TTLL5 stained the basal body of photoreceptor cells in rat and the centrosome of the spermatozoon flagellum in humans, suggesting a common mechanism of action in these two cell types. Taken together, our data indicate that mutations in TTLL5 delineate a novel, allele-specific syndrome causing defects in two as yet pathogenically unrelated functions, reproduction and vision.
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| 28. |
- Bengtsson Lindberg, Marie, et al.
(författare)
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Multifocal visual evoked potentials-a method study of responses from small sectors of the visual field.
- 2005
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1872-8952 .- 1388-2457. ; 116:8, s. 1975-1983
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Tidskriftsartikel (refereegranskat)abstract
- Objective: A method study of the mfVEP technique to establish a standardised way to identify stable response components from small areas in all parts of the visual field and a test-retest reliability study. Methods: MfVEP was recorded from 26 healthy volunteers. Results: Two response components could be clearly identified. The latencies corresponded to those of the traditional VEP response (N75 and P100). The visual field was divided into 12 sectors. A characteristic pattern was obtained. Component I was mainly negative in the upper sectors and positive in the lower sectors. Component II was positive in the upper sectors and negative in the lower ones. Most of the sectors with missing responses were the ones adjacent to the horizontal meridian, corresponding to the phase reversals. In a test-retest reliability study, the amplitude and latency measurements of the second test were plotted against those of the first test. Correlation coefficients between 0.84 and 0.93 were obtained. Conclusions: The mfVEP allows a reliable quantification of two response components from small parts of the visual field. Significance: This paper suggests that mfVEP could be a valuable supplement to the traditional VEP for exploring restricted parts of the visual pathways.
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| 29. |
- Berglund, Mats, et al.
(författare)
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Treatment of alcohol abuse: an evidence-based review.
- 2003
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Ingår i: Alcoholism: Clinical and Experimental Research. - 0145-6008. ; 27:10, s. 1645-1656
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Tidskriftsartikel (refereegranskat)abstract
- This article represents the proceedings of a symposium at the 2002 annual meeting of the Research Society on Alcoholism in San Francisco, CA, organized and cochaired by Mats Berglund and Sten Thelander. The presentations were (1) Preventive interventions against hazardous consumption of alcohol, by Mikko Salaspuro; (2) Treatment of alcohol withdrawal, by Johan Franck; (3) Psychosocial treatment for alcohol problems, by Sven Andréasson and Agneta Öjehagen; and (4) Pharmacological treatment of alcohol dependence, by Mats Berglund.
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| 30. |
- Branham, Kari, et al.
(författare)
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Mutations in RPGR and RP2 Account for 15% of Males with Simplex Retinal Degenerative Disease
- 2012
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 53:13, s. 8232-8237
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine the proportion of male patients presenting simplex retinal degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and RP2. METHODS. Simplex males were defined as patients with no known affected family members. Patients were excluded if they had a family history of parental consanguinity. Blood samples from a total of 214 simplex males with a diagnosis of retinal degeneration were collected for genetic analysis. The patients were screened for mutations in RPGR and RP2 by direct sequencing of PCR-amplified genomic DNA. RESULTS. We identified pathogenic mutations in 32 of the 214 patients screened (15%). Of the 29 patients with a diagnosis of COD/CORD, four mutations were identified in the ORF15 mutational hotspot of the RPGR gene. Of the 185 RP patients, three patients had mutations in RP2 and 25 had RPGR mutations (including 12 in the ORF15 region). CONCLUSIONS. This study represents mutation screening of RPGR and RP2 in the largest cohort, to date, of simplex males affected with RP or COD/CORD. Our results demonstrate a substantial contribution of RPGR mutations to retinal degenerations, and in particular, to simplex RP. Based on our findings, we suggest that RPGR should be considered as a first tier gene for screening isolated males with retinal degeneration. (Invest Ophthalmol Vis Sci. 2012;53:8232-8237) DOI:10.1167/iovs.12-11025
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| 31. |
- Cardiakidis Myers, Anna, et al.
(författare)
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Intravitreal Injection of Triamcinolone Acetonide into Healthy Rabbit Eyes Alters Retinal Function and Morphology
- 2013
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 38:6, s. 649-661
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study the effects of intravitreally injected triamcinolone acetonide (TA) and/or its preservative benzyl alcohol (BA) in healthy rabbit retina. Methods: Forty-eight rabbits (aged 4 months, body weight approximate to 3 kg) were randomized into four groups (n=12). They were examined with electroretinography (ERG) prior to drug exposure, and then injected intravitreally with a combination of TA and BA, TA without BA, BA alone or a balanced saline solution (BSS). The electroretinograms were assessed 1 week and 7 weeks post-injection. The rabbits were euthanized and the sectioned retinas were studied. Immunohistochemical analysis was performed on rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Muller cells. Results: Rabbits injected with BA showed a significantly lower rod-mediated b-wave amplitude than the controls 1 week after injection. TA-injected rabbits demonstrated significantly higher a- and b-wave amplitudes in the total retinal response than the controls 1 week post-injection. The rabbits injected with TA+BA demonstrated a significantly higher b-wave amplitude in the total retinal response than the controls 1 week after injection. The significantly higher a-wave amplitude in the total retinal response remained in the TA-injected rabbits 7 weeks after injection. Immunohistochemistry revealed that protein kinase C alpha (PKC alpha) was down-regulated in both the perikarya and the axons of bipolar cells in histological sections from rabbit retina injected with TA+BA, BA and TA. Conclusions: Intravitreal injection of the preservative BA reduces the isolated rod-mediated retinal response in the rabbit, transiently and selectively. Intravitreal injection of TA increases the total retinal response in the rabbit up to seven weeks after injection. The effects observed are not only limited to retinal function, but also include changes in the expression of PKC alpha in rod bipolar cells, indicating drug-related interference with normal retinal physiology in the healthy rabbit eye.
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| 32. |
- Cardiakidis Myers, Anna, et al.
(författare)
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Retinal function and morphology in rabbit after intravitreal injection of VEGF inhibitors.
- 2012
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 37:5, s. 399-407
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose/Aim: To explore changes in morphology and function in the rabbit retina after intravitreal high-dose injection of three commonly used VEGF inhibitors. Materials and methods: Forty-eight rabbits of mixed strain (6 months of age, body weight ≈ 3 kg) were randomized into four groups (n = 12). They were examined with full-field electroretinography (ERG) and with multifocal electroretinography (mf ERG) prior to drug exposure. The rabbits were then injected intravitreally with bevacizumab, ranibizumab, pegaptanib, or with a balanced saline solution. The dose of VEGF inhibitor was chosen to achieve a vitreous concentration approximately three times higher than the one clinically used in the adult human eye. ERG was then performed 8 weeks postinjection, and mf ERG 9 weeks postinjection. After 9 weeks, the rabbits were sacrificed and the sectioned retina was studied. Immunohistochemical analysis was performed of rods, cones, rod bipolar cells, horizontal cells, and amacrine cells. Results: Rabbits injected with VEGF inhibitors all showed significantly lower amplitude of the dark-adapted b-wave rod-mediated response to dim light, compared to the rabbits injected with BSS. The a wave (reflecting photoreceptor function) in the response to single flash white light was however not affected. Immunohistochemistry revealed a significant reduction in PKC labeling of rod bipolar cells in pegaptanib and ranibizumab injected eyes whereas bevacizumab injected eyes displayed normal PKC labeling. No apparent morphological change was seen with markers for remaining retinal cells. Conclusions: Our results indicate that the use of high-dose intravitreal VEGF inhibitors in the rabbit eye affects rod-mediated retinal function and PKC expression in rod bipolars cells for at least 9 weeks after drug administration. The three VEGF inhibitors influence the retina slightly differently. These results are important for the understanding of drug action and when devising therapeutical strategies in new areas such as retinopathy of prematurity where vitreous volume is significantly lower compared to the adult eye.
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| 33. |
- Cardiakidis Myers, Anna, et al.
(författare)
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Retinal Function and Morphology in the Rabbit Eye after Intravitreal Injection of the TNF Alpha Inhibitor Adalimumab.
- 2014
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 39:11, s. 1106-1116
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Aim: To study the effects of the tumor necrosis factor alpha inhibitor adalimumab on rabbit retina after injection into the vitreous body. Methods: Forty-eight rabbits of mixed strain (9-12 months old, weighing ≈ 3.5 kg) were randomized into four groups. Adalimumab was injected at one of two concentrations (1.25 mg or 2.5 mg) into the eyes of two groups, and balanced salt solution into the eyes of the third group. The fourth group acted as controls. Full-field electroretinography (ffERG) was performed before injection and 1 and 6 weeks post-injection. At 6 weeks post-injection the rabbits were euthanized and the sectioned retinas were studied. Retinal histology was studied with hematoxylin-eosin staining. Immunohistochemical analysis was performed on rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Müller cells. Results: No significant difference in ffERG amplitudes or implicit times was observed between the four groups at any time point. Histological and immunohistochemical findings were similar in all groups. Conclusions: Injection of adalimumab into the vitreous body of healthy rabbits, at doses up to 2.5 mg, does not appear to be toxic to the rabbit retina.
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| 34. |
- Cederlund, Martin, et al.
(författare)
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Vitreous levels of oxidative stress biomarkers and the radical-scavenger α(1)-microglobulin/A1M in human rhegmatogenous retinal detachment.
- 2013
-
Ingår i: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 1435-702X .- 0721-832X. ; 251:3, s. 725-732
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To explore oxidative stress and the radical scavenger α(1)-microglobulin (A1M) in the vitreous body of human eyes with primary rhegmatogenous retinal detachment (RRD). METHODS: Levels of carbonyl groups, a marker of oxidative stress, and A1M were measured by ELISA and RIA in 14 vitreous samples derived from patients suffering from RRD, and compared with 14 samples from macula hole (MH) patients. Carbonyl group and A1M levels in RRD samples were statistically related to detachment characteristics. Analysis of total protein level, SDS-PAGE, and Western blotting of A1M was also performed. In a separate experiment, mRNA expression of A1M was measured by RT-PCR in rat retina explants. RESULTS: Levels of carbonyl groups and A1M varied widely in RRD vitreous samples, but were significantly higher in samples derived from eyes with large detachment area and macula-off status, while the presence of vitreous hemorrhage did not show any significant correlation. Compared with MH samples, RRD samples displayed significantly higher levels of A1M, whereas changes in total protein levels and carbonyl groups were not significant. Novel forms of A1M, not previously seen in plasma, were found in the vitreous body by Western blotting. Furthermore, A1M expression was seen in rat retina explants and was upregulated after 24 h of culturing. CONCLUSION: Oxidative stress is a prominent feature of human eyes with primary RRD, and is directly related to detachment severity. Affected eyes can launch a protective response in the form of the radical scavenger A1M possibly derived from the retina. The results thus indicate potential therapeutic cell loss prevention in RRD by employing the endogeneous radical scavenger A1M.
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| 35. |
- Chang, Bo, et al.
(författare)
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A homologous genetic basis of the murine cpfl1 mutant and human achromatopsia linked to mutations in the PDE6C gene
- 2009
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 106:46, s. 19581-19586
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Tidskriftsartikel (refereegranskat)abstract
- Retinal cone photoreceptors mediate fine visual acuity, daylight vision, and color vision. Congenital hereditary conditions in which there is a lack of cone function in humans cause achromatopsia, an autosomal recessive trait, characterized by low vision, photophobia, and lack of color discrimination. Herein we report the identification of mutations in the PDE6C gene encoding the catalytic subunit of the cone photoreceptor phosphodiesterase as a cause of autosomal recessive achromatopsia. Moreover, we show that the spontaneous mouse mutant cpfl1 that features a lack of cone function and rapid degeneration of the cone photoreceptors represents a homologous mouse model for PDE6C associated achromatopsia.
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| 36. |
- Crafoord, Sven, et al.
(författare)
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Experimental vitreous tamponade using polyalkylimide hydrogel
- 2011
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Ingår i: Graefe's Archives for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 0721-832X .- 1435-702X. ; 249:8, s. 1167-74
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate polyalkylimide as a possible vitreous tamponading agent.METHODS: A 20-gauge pars plana vitrectomy and posterior vitreous detachment were performed in the right eye of six pigmented rabbits. Approximately 1 ml of viscoelastic gel, polyalkylimide (Bio-Alcamid) was thereafter injected into the vitreous space. Full-field ERG and intraocular pressure (IOP, Tonopen) was measured pre-and postoperatively at regular intervals up to 28 days. At day 6 or 28, the rabbits were sacrificed and the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy.RESULTS: The viscoelastic hydrogel was successfully injected, and remained translucent with preserved gel properties throughout the postoperative period. The postoperative IOP was unchanged compared to preoperative values. Five of six eyes displayed retinal edema or pigmentary changes centrally while the periphery appeared intact. ERG recordings showed a radical decrease in rod- and cone-derived B-wave amplitudes. Histological examination confirmed varying degrees of edema combined with neuronal cell death within the retinal layers in the central part of the fundus, while the peripheral part appeared intact.CONCLUSION: Polyalkylimide displays favourable physical properties when used as a vitreous tamponade. However, the hydrogel causes functional and morphological retinal damage when in direct contact with the inner retina. Possible pathological mechanisms include osmotic imbalance and direct toxic effects, and modification of biochemical properties is warranted before clinical use will be possible.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Eksandh, Louise, et al.
(författare)
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Different clinical expressions in two families with Stargardt's macular dystrophy (STGD1)
- 2001
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 79:5, s. 524-530
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the clinical expressions, with emphasis on electrophysiological examinations, in two Swedish families with Stargardt's macular dystrophy (STGD1). Methods. Two pairs of siblings with STGD1, for whom diagnosis had been confirmed by genetic linkage to the ABCA4 gene region, were examined regarding visual acuity, kinetic perimetry, fundus photography, full-field ERG and multifocal ERG (MERG). Possible disease-causing mutations were screened for by DNA sequencing of selected regions of the ABCA4 gene. Results. All STGD1 patients, had visual acuity 0.07-0.1. The two families presented different fundus appearances, MERGs and implicit times on. 30 Hz flicker white light full-field ERGs. Genetic analysis revealed one unique sequence variation in exon 19 of the ABCA4 gene, in one allele from the patients of one of the families. This point mutation causes the amino acid substitution T972N in the ABCR protein. Conclusion. Two pairs of siblings with STGD1 presented two different expressions of the disease regarding the distribution of the retinal dysfunction. One possible molecular explanation to the different clinical expressions may be the T972N substitution present in the ABCR protein in one of the STGD1 families investigated.
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| 41. |
- Eksandh, Louise, et al.
(författare)
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Full-field ERG in patients with Batten/Spielmeyer-Vogt disease caused by mutations in the CLN3 gene.
- 2000
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Ingår i: Ophthalmic genetics. - 1381-6810. ; 21:2, s. 69-77
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate, using full-field ERG, the retinal function in patients with Batten/Spielmeyer-Vogt disease caused by mutations in the CLN(3) gene. METHODS: Batten disease status of five patients was confirmed by the presence of vacuolated lymphocytes in peripheral blood and the identification of mutations in the Batten disease gene (CLN(3)). Visual acuity, fundus appearance, and full-field ERG were examined in all patients (age 4-19 years). The examination was repeated in one patient after 16 months. RESULTS: Three unrelated patients were homozygous for the most common mutation in CLN(3), the 1.02 kb deletion; two patients (sisters) were heterozygous for the 1.02 kb deletion and an as yet unidentified mutation in the CLN(3) gene. Full-field ERG recordings in all five patients demonstrated no rod responses and only small remaining cone responses, which could be detected with 30 Hz-flicker stimulation. Re-examination of a six-year-old girl after 16 months revealed a fast progression of the retinal degeneration. CONCLUSION: Full-field ERG recordings in Batten disease patients, both homozygous and heterozygous for the 1.02 kb deletion in the CLN( 3) gene, confirm retinal degeneration to be severe, widespread, and with a rapid progression early in the disease course. The onset of visual failure may be delayed when compared to the classic disease course, particularly in patients who are not homozygous for the most common CLN(3) mutation, a 1.02 kb deletion. In that case, the disease progression in terms of other symptoms may also be further delayed.
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| 42. |
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| 43. |
- Ekström, Ulf, et al.
(författare)
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A Swedish family with a mutation in the peripherin/RDS gene (Arg-172-Trp) associated with a progressive retinal degeneration
- 1998
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Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1744-5094 .- 1381-6810. ; 19:3, s. 149-156
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To clinically characterize a Swedish family with autosomal dominant retinitis pigmentosa due to a mutation, Arg-172-Trp, in the peripherin/RDS gene. METHODS: Full clinical evaluation including kinetic visual field testing, measurement of dark-adaptation threshold, and full-field electroretinography in seven patients with autosomal dominant retinitis pigmentosa and three healthy family members. Denaturing gradient gel electrophoresis (DGGE) was used for mutation screening in seven patients and six healthy members of the family. RESULTS: Three of four siblings from the middle generation and four of the younger generation were heterozygous for the peripherin /RDS Arg-172-Trp mutation. The mutation segregated with the disease. Visual acuity decreased progressively with age and visual fields were moderately constricted in young patients, while central scotoma and constriction of the fields were detected in the family members above 50 years of age. The results from full-field electrography were comparable with a widespread retinal degeneration. CONCLUSIONS: Earlier, the peripherin/RDS Arg-172-Trp mutation was associated primarily with a macular degeneration phenotype. One previous study indicated that this mutation also can give rise to a degeneration of the more peripheral parts of the retina. In the present study, a widespread retinal degeneration is seen in the patients above 50 years of age, carrying the Arg-172-Trp mutation.
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| 44. |
- Ekström, Ulf, et al.
(författare)
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Detection of alterations in all three exons of the peripherin/RDS gene in Swedish patients with retinitis pigmentosa using an efficient DGGE system
- 1998
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Ingår i: Molecular Pathology. - 1366-8714. ; 51:5, s. 287-291
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To develop a sensitive mutation screening procedure suitable for routine analysis of the peripherin/RDS gene, and to estimate the nature and prevalence of peripherin/RDS gene mutations in Swedish patients with autosomal dominant retinitis pigmentosa. METHODS: To make the method as sensitive as possible, as many as eight segments, covering the three exons and the flanking intron sequences of the peripherin/RDS gene, were analysed by denaturing gradient gel electrophoresis. A group of 38 Swedish patients with a clinical diagnosis of autosomal dominant retinitis pigmentosa were screened for mutations in the peripherin/RDS gene. RESULTS: Three point mutations were found in four of the patients and five polymorphisms were defined. One mutation in exon 1, R172W, has been described previously in other ethnic groups as causing a macular degeneration. Another mutation, in exon 2 and causing the substitution F211L, was found in two unrelated patients. A third mutation, resulting in the likely non-pathogenic substitution S289L, as well as a polymorphism not reported previously, was found in exon 3. CONCLUSIONS: The screening procedure described allows detection of mutations in all of the exons, including the polymorphic 5' and 3' ends of the gene, and is therefore suitable for routine screening of peripherin/RDS gene defects in patients with autosomal dominant retinitis pigmentosa. The frequency of mutations found in the Swedish patient group indicates that defects in the peripherin/RDS gene might be a more common cause of autosomal dominant retinitis pigmentosa than was thought previously.
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| 45. |
- Ekström, Ulf, et al.
(författare)
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Phenotypic expression of autosomal dominant retinitis pigmentosa in a Swedish family expressing a Phe-211-Leu variant of peripherin/RDS
- 1998
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Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1744-5094 .- 1381-6810. ; 19:1, s. 27-37
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To characterize the clinical phenotype, with emphasis on electrophysiology, of members of a Swedish family with autosomal dominant retinitis pigmentosa due to a novel mutation, F211L, in the peripherin/RDS gene. METHODS: Nine patients with autosomal dominant retinitis pigmentosa and two healthy family members underwent a full clinical evaluation including kinetic visual field testing, measurement of dark adaptation threshold, and full-field electroretinography. Blood samples were collected and DNA analysis was performed using denaturing gradient gel electrophoresis (DGGE). RESULTS: The grandfather, six of seven siblings from the middle generation, and two young boys carried the mutation F211L in the peripherin/RDS gene. The mutation segregated with the clinical presentation of disease. Fundus examination revealed mainly macular atrophy. All assessed parameters of retinal function (visual acuity, dark adaptation threshold, visual fields, and full-field electroretinograms) demonstrated a successive reduction with increasing age. Full-field electroretinograms showed a diminished rod response in all affected individuals and a reduction of the cone b-wave amplitudes with increasing age, indicating retinitis pigmentosa. In the affected family members, the disease seems to progress at a similar rate with increasing age. CONCLUSIONS: The peripherin/RDS gene mutation F211L is associated with a clinical phenotype and includes early loss of rod function and successive reduction of cone function with increasing age, but impressively well-preserved visual acuity and visual fields in young and middle-aged patients and moderately reduced vision in the old patient. Compared to previously described phenotypes segregating with mutations in the peripherin/RDS gene, the present family demonstrates a more benign clinical phenotype, which is concordant within the family.
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| 46. |
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Envar sin egen Falstaff, fakir
- 2012
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Samlingsverk (redaktörskap) (populärvet., debatt m.m.)abstract
- Antologi med nytryck av biografiska och litteraturvetenskapliga texter om Axel Wallengren ("Falstaff, fakir") och dennes författarskap, tidigare publicerade i spridda skrifter under perioden 1901-1989. Förord av Carlhåkan Larsén. Bildurval, bildtexter och författarpresentationer av Fredrik Tersmeden.
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| 47. |
- Forshaw, Thomas Richard Johansen, et al.
(författare)
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Full-Field Electroretinography Changes Associated with Age-Related Macular Degeneration : A Systematic Review with Meta-Analyses
- 2022
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Ingår i: Ophthalmologica. - : S. Karger AG. - 0030-3755 .- 1423-0267. ; 245:3, s. 195-203
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Forskningsöversikt (refereegranskat)abstract
- Background: The aim of this study was to systematically review the literature and to perform meta-analyses on full-field electroretinography (ffERG) between healthy controls and age-related macular degeneration (AMD) to map the extent of retinal dysfunction. Summary: We systematically searched 11 databases on 3 March 2021. Eligible studies had to measure retinal function using ffERG in eyes with AMD and in healthy controls. We extracted data on a-wave and b-wave function in dark- and light-adapted ffERG and calculated summary estimates on differences between eyes with AMD and controls using weighted mean differences (WMD). Subgroup analyses were made for early and late AMD. Six studies (n = 481 eyes) were eligible for review (301 with any AMD, 180 controls). For dark-adapted data, any AMD was associated with reduced a-wave amplitude (WMD: -17.16 μV; 95% CI: -31.79 to -2.52 μV; p = 0.02) and b-wave amplitude (WMD: -28.70 μV; 95% CI: -51.40 to -6.01 μV; p = 0.01). For light-adapted data, any AMD was associated with longer a-wave implicit time (WMD: 0.92 ms; 95% CI: 0.12-1.72 ms; p = 0.02), reduced b-wave amplitude (WMD: -13.26 μV; 95% CI: -18.64 to -7.88 μV; p < 0.0001), and longer b-wave implicit time (WMD: 0.69 ms; 95% CI: 0.30-1.08 ms; p = 0.0006). Subgroup analyses found that these changes were only statistically significant in eyes with late AMD, not early AMD. Key Messages: Reduced retinal function on ffERG is present in eyes with AMD, in particular those with late AMD. These findings suggest that AMD is a pan-retinal disease with AMD-associated photoreceptor dysfunction beyond the macula.
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| 48. |
- Forshaw, Thomas Richard Johansen, et al.
(författare)
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Full-field Electroretinography in Age-related Macular Degeneration : can retinal electrophysiology predict the subjective visual outcome of cataract surgery?
- 2020
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 98:7, s. 693-700
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Predicting the visual gain from cataract surgery when the main cause of vision loss is age-related macular degeneration may be difficult and warrants the need for an objective predictor of subjective outcome. Full-field electroretinography is an objective measure of overall retinal function. We therefore wanted to study if full-field electroretinography can predict subjective visual outcome using visual function questionnaire. Methods: Thirty-one patients with age-related macular degeneration operated for bilateral cataract underwent full-field electroretinography preoperatively. Full-field electroretinography was performed according to International Society for the Clinical Electrophysiology of Vision standards using a Ganzfeld bowl (RETI-port/scan 21, Roland, Berlin) and Dawson–Trick–Litzkow fibre electrodes. Vision-related quality of life was measured using the National Eye Institute Visual Function Questionnaire-39 before first-eye surgery and 4.12 ± 2.11 months after second-eye surgery. Results: Mean change in composite visual function questionnaire score after cataract surgery was 9.2 ± 11.9. The patients were divided into three groups: visual function questionnaire composite score increase >10 (n = 17); no change (n = 8); and decrease (n = 6). In the dark-adapted full-field electroretinography responses, we found a significant difference between the three groups in the 0.01 b-wave amplitude (p = 0.05), the 10.0 b-wave amplitude (p = 0.04) and a near-significant difference in 3.0 a-wave amplitude (p = 0.09). Other dark-adapted responses (the 3.0 b-wave and 10.0 a-wave) did not show any significant differences between the three groups, and neither did the light-adapted responses. Conclusion: Patients with low dark-adapted responses on full-field electroretinography preoperatively experience a decrease in subjective vision-related quality of life, suggesting that maintained rod function before cataract surgery may be important.
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| 49. |
- Friedman, James S., et al.
(författare)
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Mutations in a BTB-Kelch Protein, KLHL7, Cause Autosomal-Dominant Retinitis Pigmentosa
- 2009
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 84:6, s. 792-800
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Tidskriftsartikel (refereegranskat)abstract
- Retinitis pigmentosa (RP) refers to a genetically heterogeneous group of progressive neurodegenerative diseases that result in dysfunction and/or death of rod and cone photoreceptors in the retina. So far, 18 genes have been identified for autosomal-dominant (ad) RP. Here, we describe an adRP locus (RP42) at chromosome 7p15 through linkage analysis in a six-generation Scandinavian family and identify a disease-causing mutation, c.449G -> A (p.S150N), in exon 6 of the KLHL7 gene. Mutation screening of KLHL7 in 502 retinopathy probands has revealed three different missense mutations in six independent families. KLHL7 is widely expressed, including expression in rod photoreceptors, and encodes a 75 kDa protein of the BTB-Kelch Subfamily within the BTB superfamily. BTB-Kelch proteins have been implicated in ubiquitination through Cullin E3 ligases. Notably, all three putative disease-causing KLHL7 mutations are within a conserved BACK domain; homology modeling suggests that mutant amino acid side chains can potentially fill the cleft between two helices, thereby affecting the ubiquitination complexes. Mutations in an identical region of another BTB-Kelch protein, gigaxonin, have previously been associated with giant axonal neuropathy. Our studies suggest an additional role of the ubiquitin-proteasome protein-degradation pathway in maintaining neuronal health and in disease.
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| 50. |
- Friedman, James S., et al.
(författare)
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Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration
- 2006
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 79:6, s. 1059-1070
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Tidskriftsartikel (refereegranskat)abstract
- The rd3 mouse is one of the oldest identified models of early-onset retinal degeneration. Using the positional candidate approach, we have identified a C -> T substitution in a novel gene, Rd3, that encodes an evolutionarily conserved protein of 195 amino acids. The rd3 mutation results in a predicted stop codon after residue 106. This change is observed in four rd3 lines derived from the original collected mice but not in the nine wild-type mouse strains that were examined. Rd3 is preferentially expressed in the retina and exhibits increasing expression through early postnatal development. In transiently transfected COS-1 cells, the RD3-fusion protein shows subnuclear localization adjacent to promyelocytic leukemia-gene-product bodies. The truncated mutant RD3 protein is detectable in COS-1 cells but appears to get degraded rapidly. To explore potential association of the human RD3 gene at chromosome 1q32 with retinopathies, we performed a mutation screen of 881 probands from North America, India, and Europe. In addition to several alterations of uncertain significance, we identified a homozygous alteration in the invariant G nucleotide of the RD3 exon 2 donor splice site in two siblings with Leber congenital amaurosis. This mutation is predicted to result in premature truncation of the RD3 protein, segregates with the disease, and is not detected in 121 ethnically matched control individuals. We suggest that the retinopathy-associated RD3 protein is part of subnuclear protein complexes involved in diverse processes, such as transcription and splicing.
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