| 1. |
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| 2. |
- Bro, T., et al.
(författare)
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Strain out a gnat and swallow a camel? - vision and driving in the Nordic countries
- 2018
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X. ; 96:6, s. 623-630
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Tidskriftsartikel (refereegranskat)abstract
- Purpose This study describes the present legislation for visual requirements for driving in the Nordic countries in relation to the European Driving License Directive. MethodsResultsInformation about the formal legislation was gathered from each countries legal text. Further information about the implementation and common practices were achieved from national authorities in vision and driving. Even though the Nordic countries use the same framework of legislation, the implementation varies widely. Sweden and Norway have more specified visual field requirements than the others. On the other hand, no periodic testing of visual acuity (VA) is performed in Sweden as in all other Nordic countries. Physicians on Iceland are not obliged to report a person no longer fulfilling the visual requirements, as in other Nordic countries. In Denmark, Finland and Norway a person may apply for dispensation from the requirements by performing a practical driving test. In Sweden, a person applying for dispensation can undergo a traffic simulator test. ConclusionBecause of the national legislation in the Nordic countries, a person with a visual impairment may be given different permissions depending on which country they live in. As the inhabitants in the Nordic countries frequently cross the regional borders, a harmonization of the legislation would be of value. More research in this field could provide future standards, combining the greatest autonomy with the highest possible safety.
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| 3. |
- Cardell, Kristina, 1964-, et al.
(författare)
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Hepatitis B vaccination in relatives to known non-responders : A family study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Hepatitis B can be prevented by hepatitis B vaccine in most individuals. However about 5 –10% of all individuals fail to produce a protective antibody level to hepatitis B surface antigen(anti-HBs), after standard vaccination procedure with three vaccine doses. The mechanismsfor non-response are multi-factorial and not clearly understood. Non-response in this studywas defined as anti-HBs < 10 mIU/ml after at least 4 doses of intradermal hepatitis B vaccine.In this study we vaccinated relatives to known non-responders to hepatitis B vaccine. Thestudy subjects were chosen among relatives to non-responders with known HLA class IIhaplotypes. Recombinant hepatitis B vaccine was administered intradermally at 0, 1 and 6months. For those with anti-HBs <10 mIU/ml after three doses an additional dose was givenfollowed by new anti-HBs measurement. A total of 8 probands and 26 relatives wereincluded. Of the 26 relatives 15/26 (58%) responded to the vaccination schedule compared tothe expected 90-95%. This data therefore support the theory that genetic factors play animportant role in the antibody response to hepatitis B vaccine. The study population wasthough too small to conclude the role of specific genetic factors related to response and nonresponse.
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| 4. |
- Ekström, Curt, 1944-
(författare)
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Studies on the Epidemiology of Open-angle Glaucoma
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glaucoma is a common disease in the elderly population. Open-angle glaucoma (OAG) is the predominant form of glaucoma. Chronic simple glaucoma and capsular glaucoma, characterized by the occurrence of pseudoexfoliation in the anterior eye segment, are the most frequent types of OAG. The purpose of the present thesis was to study the epidemiology of OAG in the municipality of Tierp, whose population has a high exposure to pseudoexfoliation.In a case-finding study, the prevalence of known cases of OAG by December 31, 1983 was estimated to 1.4% in people ≥45 years of age. Sixty-three percent of all cases had capsular glaucoma. Patients with advanced glaucoma were older, had had the disease for longer, had higher mean initial intraocular pressure, and had more extensive visual field defects at the time of diagnosis.A population survey of people 65–74 years of age was conducted in 1984–86. The prevalence of OAG was 5.3%. Pseudoexfoliation was found in 17%, being more common in females. Pseudoexfoliation was associated with OAG only in people previously diagnosed with the disease (odds ratio = 16). In cases detected at the survey, an intraocular pressure ≥20 mmHg was a serious risk factor of having OAG (odds ratio = 9.7).In a 5-year follow-up study of participants in the population survey, increased intraocular pressure and pseudoexfoliation were recognized as independent risk factors for the development of OAG (standardized risk ratios = 3.4 and 9.8, respectively). Interaction between increased intraocular pressure and pseudoexfoliation was indicated. By May 2006, the incidence of OAG was estimated to 7.1 per 1,000 person-years. The incidence of capsular glaucoma was more than twice that of chronic simple glaucoma.The prevalence and incidence of OAG was higher than that reported from other studies conducted on Caucasian populations. The probable explanation for this finding is exposure to pseudoexfoliation.
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| 5. |
- Ericsson, Carolina, et al.
(författare)
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Risk för att prolaktinom växer under graviditet
- 2012
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Ingår i: Läkartidningen. - 0023-7205. ; 2012:25, s. 1226-1228
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the results of visual field examinations during pregnancy in women with prolactinoma. Materials and methods: A retrospective study of 73 women with prolactinoma (97 pregnancies) who were examined at the neuro-ophthalmologic clinic at Sahlgrenska Universitetssjukhuset 2002-2010. Results: One of 62 women with microprolactinoma (1.2 per cent of the pregnancies and 1.6 per cent of the women) and 1 of 11 women with macroprolactinoma (9.1 per cent of the pregnancies and 7.1 per cent of the women) developed visual field defects during pregnancy due to tumour growth. Both women experienced visual symptoms. Conclusions: This study confirms that tumour growth causing visual field defects is rare during pregnancy, although more common with macro- than with microprolactinomas. Based on this and previous studies we conclude that women with microprolactinoma do not need visual field examinations during pregnancy due to a very low risk of non-symptomatic tumour growth, while for women with macroprolactinoma repeated visual field examinations during pregnancy should be considered.
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| 6. |
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| 7. |
- Heijl, Anders, et al.
(författare)
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Nordic research in ophthalmology.
- 2005
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Ingår i: Acta ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 83:3, s. 278-88
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Nordic ophthalmologists and vision scientists are active in many fields of eye research. This is most evident at the biannual Nordic Congress of Ophthalmology, most recently held in Malmö in June 2004. The authors here review some of the research in vision and ophthalmology presented at this meeting or published recently by Nordic scientists. This paper does not represent a comprehensive review of all Nordic research in the field, but attempts to give an overview of some of the activities underway in eye research in this part of the world.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Holmgren, Per, et al.
(författare)
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Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19
- 2004
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 0146-4760 .- 1945-2403. ; 28:2, s. 94-104
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Tidskriftsartikel (refereegranskat)abstract
- Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (± standard deviation) S/R ratio for citalopram was 0.67 ± 0.25 and for desmethylcitalopram, 0.68 ± 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.
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| 12. |
- Holmlund, Gunilla, et al.
(författare)
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Y-chromosome STR haplotypes in Sweden
- 2006
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Ingår i: Forensic Science International. - : Elsevier. - 0379-0738 .- 1872-6283. ; 160:1, s. 66-79
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Tidskriftsartikel (refereegranskat)abstract
- A total of 708 men, with Swedish names, from different parts of Sweden have been typed for the Y-chromosome minimal haplotype STR markers DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393 and DYS385. Of these, 403 men were of geographically undefined Swedish origin and the rest, 305, from seven defined geographical regions. PCR-products were detected by ABI377 using sequenced allelic ladders. An evaluation of the 708 chromosomes revealed 423 different haplotypes. Only 100 of the haplotypes were found more than once. The over all haplotype diversity was 0.994. The haplotype 14, 12, 28, 23, 10, 11, 13, 14-14 has the highest frequency of 5.79% and is significantly Swedish, when compared to other European populations.
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| 13. |
- Jablonowska, Barbro, et al.
(författare)
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Analyses of human leukocyte antigen (HLA-DRB1 and HLA-G alleles in couples with unexplained recurrent spontaneous abortion : typing by using the Polymerase Chain Reaction method
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Increased parental Human Leukocyte Antigen (HLA) sharing has been repmted in couples witb history of unexplained recurrent spontaneous abmtion (RSA). Parental HLA sharing increases the risk of feto-matemal histo-compatibility and potentially affects maternal alia-recognition of the fetus. HLA-G is expressed on trophoblast and is expected to play an important role during placental and fetal development. The aim of the present study was to investigate the compatibility of HLA-DRB1 alleles in the couples with unexplained RSA and to investigate the frequency of HLA-DRB1 alleles and HLA-G alleles in these couples compared with fertile controls.Methods: The frequency of HLA-DRB1 alleles in 36 couples with unexplained recurrent spontaneous abmtion, and the compatibility of HLA-DRB1 alleles between patient couples were studied using a polymerase chain reaction-sequence specific primers (PCR- SSP) method. The frequency of HLA-G alleles in 35 couples were studied using a polymerase chain reaction - single nuclotide polymorphism (PCR-SNP). As controls we used 40 fertile couples who were typed for HLA-DRB1 and HLA-G alleles.Results: There were no significant differences for HLA-DRB1 and HLA-G allele frequencies in RSA couples compared with fertile controls. There was no significant HLA-DRB1 allele sharing between the RSA couples and fertile controls.Conclusions: There is no higher HLA-DRB1 allele sharing in couples with unexplained RSA than in fettile couples. The association on allelic level between RSA and HLA-G gene was not supported by our data.
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| 14. |
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| 15. |
- Johansson, Charlotta, et al.
(författare)
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The role of optical coherence tomography in the detection of pituitary adenoma.
- 2009
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Ingår i: Acta ophthalmologica. - : Wiley. - 1755-3768 .- 1755-375X. ; 87:7, s. 776-9
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To analyse retinal nerve fibre layer (RNFL) thickness in eyes with compression of the optic chiasm by a pituitary adenoma. RNFL thickness was analysed with optical coherence tomography (OCT) and compared to visual field measurements using high-pass resolution perimetry (HRP). Methods: Sixteen eyes from eight patients with pituitary adenoma were studied. All had bitemporal visual field depression caused by compression of the optic chiasm. Patients were submitted to an ophthalmic examination more than 14 months after surgery (seven patients had undergone trans-sphenoidal and one trans-cranial adenomectomy). The examination included HRP, fundus photography and measurement of the peripapillar RNFL thickness using OCT. Results: In spite of temporal visual field depression, not all eyes showed reduced RNFL thickness by OCT. This was also true for some eyes in which RNFL was judged to be reduced on fundus photographs. Contrary to our expectations, RNFL thickness in the nasal quadrant was normal in nine of the 16 eyes. Corresponding figures for the superior, inferior and temporal quadrants were eight, six and five, respectively. The overall RNFL thickness, as measured by OCT, did not correlate well with neural capacity, which is an index of remaining retino-cortical neural channels in HRP. Conclusion: RNFL thickness as measured with OCT was reduced in most, but not all, eyes with temporal field depression caused by chiasmal compression. The pattern of RNFL loss did not correlate well with the visual field defect. Sensitivity of RNFL thickness measurement in OCT was low. The method has limited value in the diagnosis of pituitary tumour compression.
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| 16. |
- Kalaboukhova, Lada, 1975, et al.
(författare)
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An objective method for measuring relative afferent pupillary defect in glaucomatous optic neuropathy - stimulus optimization
- 2006
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Ingår i: Neuro-ophthalmology. - 0165-8107. ; 30, s. 7-15
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To develop a new technique for measuring relative afferent pupillary defect (RAPD) and to find the best stimulus parameters for detecting glaucomatous optic neuropathy. Methods: With a newly constructed pupillometer based on digital video recording, pupillary light reflexes were analyzed during alternating light stimulation. Pupil area was measured in each video frame using computer digital image analysis. The examinations were performed using different sets of stimulus-pause combinations. Subjects with unilateral or asymmetrical glaucoma were studied and compared to normals. Results: Alternating light stimulation of 0.5-s followed by 1-s pause was shown to be the best stimulus pattern for RAPD detection. Conclusion: Infrared pupillometry could distinguish eyes with glaucoma from normal eyes with good sensitivity and specificity.
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| 17. |
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| 18. |
- Kalaboukhova, Lada, 1975, et al.
(författare)
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Glaucoma follow-up by the Heidelberg retina tomograph--new graphical analysis of optic disc topography changes.
- 2006
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Ingår i: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie. - : Springer Science and Business Media LLC. - 0721-832X. ; 244:6, s. 654-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Heidelberg Retina Tomograph (HRT) is a commercially available instrument for the detection of glaucomatous damage by analysis of optic nerve head topography. The main purpose of the study was to investigate the ability of HRT to detect changes in optic disc topography indicating progression of optic neuropathy in eyes with open-angle glaucoma or, in eyes with ocular hypertension, conversion to open-angle glaucoma. METHODS: Fifty-nine subjects (34 with ocular hypertension, 25 with glaucoma) from the glaucoma service at Sahlgrenska University Hospital were included in this study. One eye of each patient was selected. All participants underwent thorough clinical examination, including HRT, high-pass resolution perimetry (HRP), and optic disk photography. After a mean follow-up time of 50 months, patients were re-examined. Based on analyses of optic disc photographs and HRP, eyes were classified into one of two groups: progressive or stable. The differences between baseline and follow-up HRT parameters in the two groups were analysed. The topographic HRT change images were also compared after digital image processing. A pixel ratio was calculated defined as the ratio between the area of pixels representing deepening of the disc surface and the total disc area. Receiver operating characteristic (ROC) curves for HRT parameters and pixel ratio were compared. RESULTS: In the group judged to have progressive optic neuropathy, a statistically significant change between baseline and follow-up examination was found for the following HRT parameters: cup shape measurement, classification index, the third moment in contour, cup/disc ratio, cup area, rim area, and area below reference). In the stable group no HRT parameters had changed significantly. A well-defined distinction between the two groups was found by comparing digitally processed HRT change images. The area under the ROC curve was larger for pixel ratio than for any of the HRT parameters. CONCLUSIONS: The HRT is a useful tool for long-term follow-up of glaucomatous optic neuropathy. Digital image processing of HRT change images could facilitate the detection of progressive change.
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| 19. |
- Kalaboukhova, Lada, 1975, et al.
(författare)
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Relative afferent pupillary defect in glaucoma: a pupillometric study.
- 2007
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Ingår i: Acta ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 85:5, s. 519-25
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study the presence of relative afferent pupillary defect (RAPD) in patients with glaucoma with the help of a custom-built pupillometer. METHODS: Sixty-five participants were recruited (32 with open-angle glaucoma and 33 healthy subjects). All underwent standard clinical examination including perimetry and optic disc photography. Pupillary light reflexes were examined with a custom-built pupillometer. Three video sequences were recorded for each subject. Alternating light stimulation with a duration of 0.5 seconds was used, followed by a 1 second pause. Mean values of pupil area ratio (PAR), pupil contraction velocity ratio (PCVR), and pupil dilation velocity ratio (PDVR) were calculated. Receiver operating characteristic (ROC) curves were constructed for each of the three parameters. Intra-individual variability was estimated. RESULTS: PAR and PDVR differed significantly between the group with glaucoma and the control group (P < 0.0001). PAR was more sensitive for glaucoma detection than the other pupillometric parameters (PCVR and PDVR). The area under the receiver operating characteristic curve was largest for PAR. At a fixed specificity of 90%, sensitivity for PAR was 86.7%. CONCLUSION: Measuring RAPD with infrared computerized pupillometry can detect optic neuropathy in glaucoma with high sensitivity and specificity. The method is fast and objective. Pupil area amplitude measurements were superior to pupil velocity measurements for the detection of RAPD in glaucoma.
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| 20. |
- Kawasaki, Aki, 1963-
(författare)
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Selective wavelength pupillometry to evaluate outer and inner retinal photoreception
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- PurposeIntrinsically photosensitive retinal ganglion cells (ipRGCs) express a unique photopigment called melanopsin. Capable of direct phototransduction, the ipRGCs are also influenced by rods and cones via synaptic inputs. Thus, the photoinput that mediates the pupil light reflex derives from both outer (rods and cones) and inner (melanopsin-mediated) retinal photoreception. This thesis has aimed to develop a pupillometric test that provides quantitative information about the functional status of outer and inner retinal photoreception in healthy eyes and in eyes with retinal degeneration. In addition to regulating the pupil light reflex, the ipRGCs signal light information for the circadian rhythm, thus, these two non-visual physiologic responses to inner retinal photoreception were examined simultaneously.MethodsPupil responses to a long and short wavelength light over a range of intensities (under conditions of light, mesopic and dark adaptation) were recorded using a customized infrared computerized pupillometer. Results were compared for two groups: patients with retinitis pigmentosa and controls. The response function threshold intensity and a half-max intensity was determined from the rod-weighted and cone-weighted pupil responses and correlated to extent of visual loss. The pupil response to light offset was assessed as a measure of direct melanopsin activation. Lastly, pupil responses to red and blue light at equal photo flux were recorded hourly during a 24-hour period and correlated to salivary melatonin concentrations in healthy subjects.ResultsIn normal eyes, the blue light evoked greater pupil responses compared to equiluminant red light. With increasing intensity, pupil contraction became more sustained which was most apparent with the brightest blue light. In patients with retinitis pigmentosa, the pupil responses mediated predominantly by rod and cone activation were significantly reduced compared to controls, (p<0.001) and the relative decrease in their contribution resulted in a greater influence of melanopsin on the post-stimulus response. Even at endstage retinal degeneration, pupil responses that derived predominantly from residual cone activity were detectable. The threshold intensity of the rod-mediated, but not cone-mediated, pupil response was also significantly reduced (p=0.006) in patients and the half-maximal intensity of rods correlated with severity of visual loss (r2=0.7 and p=0.02). In healthy controls, the melanopsin-mediated pupil response demonstrated a circadian modulation whereas the cone-mediated pupil response did not.ConclusionEarly and progressive loss of rod function in mild-moderate stages of retinitis pigmentosa is detectable and quantifiable as a progressive loss of pupillary sensitivity to extremely dim blue lights obtained under conditions of dark adaptation. In advanced stages of retinal degeneration, chromatic pupillometry is more sensitive than standard electroretinography for detecting residual levels of rod and especially cone activity. In addition, selective wavelength pupillometry can assess non-visual light-dependent functions. The timing of the post-stimulus pupil response to blue light is in phase with melatonin secretion, suggesting a circadian regulation of this pupil parameter.
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| 21. |
- Kindberg, Elin, 1981-, et al.
(författare)
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A nonsense mutation (428G→A) in the fucosyltransferase FUT2 gene affects the progression of HIV-1 infection
- 2006
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Ingår i: AIDS. - : Ovid Technologies (Wolters Kluwer Health). - 0269-9370 .- 1473-5571. ; 20:5, s. 685-689
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The human FUT2 gene encodes the α(1,2)fucosyltransferase that determines secretor status. Homozygous for the nonsense mutation are called non-secretors and are unable to express histo-blood group antigens in secretions and on mucosal surfaces. In this study we have investigated the importance of the FUT2 fucosyltransferase activity on the progress of HIV-1 infection. METHODS: Swedish blood donors (n = 276), 15 long-term non-progressors (LTNP) and 19 progressors were genotyped with respect to the nonsense mutation 428G→A in the FUT2 gene. In addition 265/276 blood donors and 19 progressors with rapid or expected progression rate were Δ32 CCR5 genotyped. RESULTS: Of 276 blood donors 218 (79%) were found to be secretor positive (se+), either homozygous (se+/+) wild type (30%) or heterozygous (se+/-) (49%) and 58 (21%) were homozygous non-secretors (se-/-). Five LTNP (33%) were found to be secretor-positive (se+/+, se+/-) and 10 (67%) se-/-. Of the 19 individuals with normal HIV-1 progression 15 (79 %) were found to be secretor positive and four (21%) were non-secretors. No frequency differences were found in the Δ32 CCR5 allele among the groups studied. CONCLUSION: Strong association (P < 0.001) was observed between the nonsense mutation 428G→A in the FUT2 gene and a slow disease progression of HIV-1 infection. © 2006 Lippincott Williams & Wilkins.
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| 22. |
- Kindberg, Elin, 1981-
(författare)
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Host genetic risk factors to viral diseases - a double-edged sword : Studies of norovirus and tick-borne encephalitis virus
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is today well known that the outcome of a certain infection depends on factors of both the host and the pathogen. Studies of host genetic susceptibility to infectious diseases aim to increase the understanding of why some individuals are more susceptible than others, to a certain infection. Knowledge of genetic susceptibility to a viral disease may be used in development of new therapeutic means, and also to recognize individuals who are at increased risk of severe symptoms if infected with a pathogen. It seems however that a risk factor for one disease may play a protective role in another situation; like a double-edged sword.In this thesis I have studied genetic factors affecting susceptibility to norovirus (NoV) and factors affecting the risk of developing tick-borne encephalitis (TBE) after infection with TBE virus (TBEV). NoV is the cause of the “winter vomiting disease”, affecting millions of people every year, and causing up to 200,000 fatalities among children in developing countries, each year. It is today recognized that the secretor status of an individual, i.e. the ability to express ABO blood groups and related antigens, in secretions and on mucosa, affect the risk of being infected by NoV. By studying authentic NoV outbreaks in Denmark, Spain and Sweden and by comparing the secretor status of affected and unaffected individuals we were able to confirm that secretor status have indeed great impact on susceptibility to some NoV strains, but also that there are strains circulating, which infect individuals regardless of secretor status.TBEV is endemic in many parts of Europe and Asia but studies have shown that 70-95% of all infections are asymptomatic or sub-clinical. Some individuals do however develop TBE, a severe disease including meningitis or encephalitis with or without myelitis. Also, many patients suffer from long-time sequelae and TBEV infections may in worst case be fatal. The reason for difference in disease outcome is not known and we have chosen to study if genetic factors affecting the immune response may play a role in disease outcome. To do this we used a prospectively collected Lithuanian material with samples from patients with TBE, AME (aseptic meningoencephalitis) and matched healthy controls. So far we have found that a deletion in chemokine receptor 5 (CCR5), a gene encoding a receptor involved in cell migration, is a risk factor for developing disease. We have also data showing that toll-like receptor 3 (TLR3), a receptor recognizing double stranded RNA (dsRNA), which is a product of TBEV replication, may instead of being protective increase the risk of TBE.
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| 23. |
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| 24. |
- Kvickström, P., et al.
(författare)
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Amaurosis fugax – delay between symptoms and surgery by specialty
- 2016
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Ingår i: Clinical Ophthalmology. - 1177-5467. ; 10, s. 2291-2296
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the time course of management of patients with amaurosis fugax and analyze differences in management by different specialties. Methods: Patients diagnosed with amaurosis fugax and subjected to carotid ultrasound in 2004–2010 at the Sahlgrenska University Hospital,Gothenburg,Sweden (n=302) were included in this retrospective cohort study,and data were collected from medical records. Results: The prevalence of significant carotid stenosis was 18.9%,and 14.2% were subjected to carotid endarterectomy. A trend of longer delay for surgery was noted for patients first consulting a general practitioner (P=0.069) as compared to hospital-based specialties. For 46.3% of the patients,an ophthalmologist was their first medical contact. No significant difference in time interval to endarterectomy was seen between ophthalmologists and neurologists/internists. Only 31.8% of the patients with significant carotid stenosis had carotid endarterectomy within 2 weeks from the debut of symptoms,and this proportion was smaller for patients residing outside the Gothenburg city area (P=0.038). Conclusion: Initially consulting an ophthalmologist does not delay the time to ultrasound or carotid endarterectomy. The overall time from symptoms to surgery is longer than recommended for a majority of the patients,especially for patients from rural areas and for patients initially consulting a general practitioner. © 2016 Kvickström et al.
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| 25. |
- Kvickström, P., et al.
(författare)
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Amaurosis fugax: Risk factors and prevalence of significant carotid stenosis
- 2016
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Ingår i: Clinical Ophthalmology. - 1177-5467. ; 10, s. 2165-2170
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to describe clinical characteristics and prevalence of carotid stenosis in patients with amaurosis fugax (AF). Method: Patients diagnosed with AF and subjected to carotid ultrasound in 2004–2010 in Sahlgrenska University Hospital, Gothenburg (n=302), were included, and data were retrospectively collected from medical records. Results: The prevalence of significant carotid stenosis was 18.9%, and 14.2% of the subjects were subjected to carotid endarterectomy. Significant associations with risk of having $70% stenosis were male sex (adjusted odds ratio [aOR]: 2.62; 95% confidence interval [CI]: 1.26–5.46), current smoking (aOR: 6.26; 95% CI: 2.62–14.93), diabetes (aOR: 3.68; 95% CI: 1.37–9.90) and previous vasculitis (aOR: 10.78; 95% CI: 1.36–85.5). A majority of the patients (81.4%) was seen by an ophthalmologist prior to the first ultrasound. Only 1.7% of the patients exhibited retinal artery emboli at examination. Conclusion: The prevalence of carotid stenosis among patients with AF is higher than has previously been demonstrated in stroke patients. An association with previously reported vascular risk factors and with vasculitis is seen in this patient group. Ocular findings are scarce. © 2016 Kvickström et al.
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| 26. |
- Langö-Warensjö, Anna, et al.
(författare)
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Haplotypes comprising subtypes of the DQB1*06 allele direct the antibody response after immunisation with hepatitis B surface antigen
- 1998
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Ingår i: Tissue Antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 52:4, s. 374-380
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Tidskriftsartikel (refereegranskat)abstract
- Two HLA class II haplotypes, HLA-[DQB1*0602; DQA1*0102; DR15] and HLA-[DQB1*0603; DQA1*0103; DRB1*1301] were found to be less common in 52 nonresponders compared with 68 responders, P<0.025 and P<0.05 respectively, after vaccination with hepatitis B surface antigen (HBsAg). Another haplotype, HLA-[DQB1*0604; DQA1*0102; DRB1*1302], had a significantly higher frequency in the nonresponders (P<0.005). The nonresponders and responders were nonsmoking, healthy individuals with an antibody concentration of <10 IU/l and >100 IU/l respectively. The three haplotypes comprise either of three different DQB1*06 subtypes. Two of the seven amino acids that differ between the two responder alleles DQB1*0602 and *0603 and the nonresponder allele *0604 are located in the peptide-binding groove of the DQB1 molecule. In addition to this finding, amino acid 86 in the DRB1 molecule seems to determine the response against HBsAg. DRB1*1301 and DR15 in the responder haplotypes have a Val at this position while the nonresponder haplotype has a Gly. These results suggest a role for both the DQB1*06 alleles and the DRB1 alleles *1301, *1302 and DR15 to direct either a response or a nonresponse against HBsAg. Sixteen HLA class II genotypes were found to be shared by 25 nonresponders and 32 responders. This finding of HLA-identical nonresponders and responders indicates an influence of other genetic factors in addition to the HLA system in the response to HBsAg.
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| 27. |
- Lilja, Ylva, et al.
(författare)
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Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging.
- 2017
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Ingår i: Journal of neurosurgery. - 1933-0693. ; 127:3, s. 569-579
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas, little is known about objective indices that may reveal risk of visual impairment caused by tumor growth that leads to compression of the anterior visual pathways. This study aimed to explore diffusion tensor imaging (DTI) as a means for objective assessment of injury to the anterior visual pathways caused by pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas, scheduled for transsphenoidal tumor resection, and 20 healthy control subjects were included in the study. A minimum suprasellar tumor extension of Grade 2-4, according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and posterior) scale, was required for inclusion. Neuroophthalmological examinations, conventional MRI, and DTI were completed in all subjects and were repeated 6 months after surgery. Quantitative assessment of chiasmal lift, visual field defect (VFD), and DTI parameters from the optic tracts was performed. Linear correlations, group comparisons, and prediction models were done in controls and patients. RESULTS Both the degree of VFD and chiasmal lift were significantly correlated with the radial diffusivity (r = 0.55, p < 0.05 and r = 0.48, p < 0.05, respectively) and the fractional anisotropy (r = -0.58, p < 0.05 and r = -0.47, p < 0.05, respectively) but not with the axial diffusivity. The axial diffusivity differed significantly between controls and patients with VFD, both before and after surgery (p < 0.05); however, no difference was found between patients with and without VFD. Based on the axial diffusivity and fractional anisotropy, a prediction model classified all patients with VFD correctly (sensitivity 1.0), 9 of 12 patients without VFD correctly (sensitivity 0.75), and 17 of 20 controls as controls (specificity 0.85). CONCLUSIONS DTI could detect pathology and degree of injury in the anterior visual pathways that were compressed by pituitary adenomas. The correlation between radial diffusivity and visual impairment may reflect a gradual demyelination in the visual pathways caused by an increased tumor effect. The low level of axial diffusivity found in the patient group may represent early atrophy in the visual pathways, detectable on DTI but not by conventional methods. DTI may provide objective data, detect early signs of injury, and be an additional diagnostic tool for determining indication for surgery in cases of pituitary adenomas.
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| 28. |
- Lindblom, Bertil, 1951, et al.
(författare)
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A multicentre, retrospective study of resource utilization and costs associated with glaucoma management in France and Sweden.
- 2006
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Ingår i: Acta ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 84:1, s. 74-83
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To assess resource utilization and costs associated with glaucoma management in France and Sweden. METHODS: A total of 267 patient records (121 in France, 146 in Sweden) with diagnoses of primary open-angle glaucoma (POAG) and ocular hypertension (OH), treated medically, were reviewed for a 2-year period (beginning during 1997-99) for relevant clinical and resource utilization data. Economic data were applied to estimate treatment costs. RESULTS: The annual cost of treating glaucoma was estimated at SEK5305 (531 euro )/patient in Sweden and 390 euro/patient in France. In both countries, medication costs comprised about half of the total costs. Surgical procedures and hospitalizations represented greater proportions of total cost in France (7.0% and 9.6%, respectively) than in Sweden (3.7% and 0.6%, respectively). CONCLUSION: Medication costs represent a high proportion of total treatment costs. These findings highlight the relative importance of medical therapy and of assessing the cost-effectiveness of medications in glaucoma.
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| 29. |
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| 30. |
- Lindblom, Bertil, 1951
(författare)
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Ögat och synen genom livet
- 2012
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Ingår i: Incitament. - 1103-503X. ; 201:1, s. 41-43
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 31. |
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| 32. |
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| 33. |
- Montelius, Kerstin, et al.
(författare)
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DNA analysis in disaster victim identification
- 2012
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Ingår i: FORENSIC SCIENCE MEDICINE AND PATHOLOGY. - : Humana Press (Springer Imprint). - 1547-769X .- 1556-2891. ; 8:2, s. 140-147
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Forskningsöversikt (refereegranskat)abstract
- DNA profiling and matching is one of the primary methods to identify missing persons in a disaster, as defined by the Interpol Disaster Victim Identification Guide. The process to identify a victim by DNA includes: the collection of the best possible ante-mortem (AM) samples, the choice of post-mortem (PM) samples, DNA-analysis, matching and statistical weighting of the genetic relationship or match. Each disaster has its own scenario, and each scenario defines its own methods for identification of the deceased.
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| 34. |
- Ostberg, Anders, et al.
(författare)
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Skövde cataract study: I. Prevalence of lens opacities in a Swedish community.
- 2006
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Ingår i: Ophthalmology. - : Elsevier BV. - 1549-4713 .- 0161-6420. ; 113:6, s. 970-5
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the prevalence of lens opacities in a well-defined Swedish population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Seven hundred inhabitants of the town of Skövde, Sweden were randomly selected and invited to an ophthalmologic examination. Invited persons were 70 to 84 years old and were assigned to 1 of 3 age groups: 70 to 74, 75 to 79, or 80 to 84. METHODS: All participants underwent visual acuity (VA) testing using the Early Treatment Diabetic Retinopathy Study acuity chart. Lens opacities were graded using the Lens Opacities Classification System III after pupil dilation. Causes of visual impairment, other than cataract, were identified by thorough ophthalmologic examination. MAIN OUTCOME MEASURE: Prevalence of lens opacities. RESULTS: Five hundred sixty-five persons underwent a complete examination (participation rate, 80.7%). As expected, the presence of lens opacities increased with age. Using a definition of cataract based on morphologic changes only, prevalences of cataract in one or both eyes were 23.5% for women and 14.0% for men in the entire cohort. If prevalence of previous cataract surgery was included, prevalence rose to 47.9% for women and 27.3% for men. In all age groups, lens opacities were denser and cataract prevalence was higher in women than in men. Consequently, VA was lower in females than in men, when other reasons for visual impairment were excluded. CONCLUSIONS: Lens opacities were common in the studied age groups and increased with age. In all studied age groups, lens opacities were denser in women than in men.
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| 35. |
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| 36. |
- Söderbäck, Erik, et al.
(författare)
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Determination of CYP2D6 gene copy number by pyrosequencing
- 2005
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 51:3, s. 522-531
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Identification of CYP2D6 alleles *5 (deletion of the whole CYP2D6 gene) and *2xN (gene duplication) is very important because they are associated with decreased or increased metabolism of many drugs. The most commonly used method for analysis of these alleles is, however, considered to be laborious and unreliable. METHODS: We developed a method to determine the copy number of the CYP2D6*5 and CYP2D6*2xN alleles by use of Pyrosequencing technology. A single set of PCR and sequencing primers was used to coamplify and sequence a region in the CYP2D6 gene and the equivalent region in the CYP2D8P pseudogene, and relative quantification between these fragments was performed. The CYP2D8P-specific Pyrosequencing peak heights were used as references for the CYP2D6-specific peak heights. RESULTS: Analysis of 200 pregenotyped samples showed that this approach reliably resolved 0-4 genome copies of the CYP2D6 gene. In 15 of these samples, the peak pattern from one analyzed position was unexpected but could be solved by conclusive results from a second position. The method was verified on 270 other samples, of which 267 gave results that corresponded to the expected genotype. One of the samples could not be interpreted. The reproducibility of the method was high. CONCLUSIONS: CYP2D6 gene copy determination by Pyrosequencing is a reliable and rapid alternative to other methods. The use of an internal CYP2D8P control as well as generation of a sequence context ensures a robust method and hence facilitates method validation.
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| 37. |
- Tillmar, Andreas, et al.
(författare)
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Analysis of linkage and linkage disequilibrium for eight X-STR markers.
- 2008
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Ingår i: Forensic science international. Genetics. - : Elsevier. - 1878-0326 .- 1872-4973. ; 3:1, s. 37-41
-
Tidskriftsartikel (refereegranskat)abstract
- X-chromosomal short tandem repeats (X-STR) have proven to be informative and useful in complex relationship testing. The main feature of X-STR markers, compared to autosomal forensic markers, is that all loci are located on the same chromosome. Thus, linkage and linkage disequilibrium may occur. The aim of this work was to study population genetic parameters of eight X-STR markers, located in four linkage groups. We present haplotype frequencies, based on 718 Swedish males, for the four linkage groups included in the Argus X-8 kit. Forensic efficiency parameters have been calculated as well as the allelic association between the tested markers for detection of linkage disequilibrium. To study the occurrences of recombination between the loci, both Swedish and Somali families were typed. A mathematical model for the estimation of recombination frequencies is presented and applied on the family samples. Our study showed that the tested markers all have highly informative forensic values and that there is a significant degree of linkage disequilibrium between the STR markers within the four linkage groups. Furthermore, based on the tested families, we also demonstrated that two of the linkage groups are partially linked. A consequence of these findings is that both linkage and linkage disequilibrium should be accounted for when producing likelihood ratios in relationship testing with X-STR markers.
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| 38. |
- Tillmar, Andreas, 1980-
(författare)
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Populations and Statistics in Forensic Genetics
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- DNA has become a powerful forensic tool for solving cases such as linking a suspect to a crime scene, resolving biological relationship issues and identifying disaster victims. Traditionally, DNA investigations mainly involve two steps; the establishment of DNA profiles from biological samples and the interpreta-tion of the evidential weight given by theses DNA profiles. This thesis deals with the latter, with focus on models for assessing the weight of evidence and the study of parameters affecting these probability figures.In order to calculate the correct representative weight of DNA evidence, prior knowledge about the DNA markers for a relevant population sample is required. Important properties that should be studied are, for example, how frequently certain DNA-variants (i.e. alleles) occur in the population, the differences in such frequencies between subpopulations, expected inheritance patterns of the DNA markers within a family and the forensic efficiency of the DNA markers in casework.In this thesis we aimed to study important population genetic parameters that influence the weight of evidence given by a DNA-analysis, as well as models for proper consideration of such parameters when calculating the weight of evi-dence in relationship testing.We have established a Swedish frequency database for mitochondrial DNA haplotypes and a haplotype frequency database for markers located on the X-chromosome. Furthermore, mtDNA haplotype frequencies were used to study the genetic variation within Sweden, and between Swedish and other European populations. No genetic substructure was found in Sweden, but strong similari-ties with other western European populations were observed.Genetic properties such as linkage and linkage disequilibrium could be im-portant when using X-chromosomal markers in relationship testing. This was true for the set of markers that we studied. In order to account for this, we pro-posed a model for how to take linkage and linkage disequilibrium into account when calculating the weight of evidence provided by X-chromosomal analysis.Finally, we investigated the risk of erroneous decisions when using DNA in-vestigations for family reunification. We showed that the risk is increased due to uncertainties regarding population allele frequencies, consanguinity and compet-ing close relationship between the tested individuals. Additional information and the use of a refined model for the alternative hypotheses reduced the risk of making erroneous decisions.In summary, as a result of the work on this thesis, we can use mitochondrial DNA and X-chromosome markers in order to resolve complex relationship in-vestigations. Moreover, the reliability of likelihood estimates has been increased by the development of models and the study of relevant parameters affecting probability calculations.
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| 39. |
- Tillmar, Andreas, 1980-, et al.
(författare)
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Using X-chromosomal markers in relationship testing: How to calculate likelihood ratios taking linkage and linkage disequilibrium into account
- 2011
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 5:5, s. 506-511
-
Tidskriftsartikel (refereegranskat)abstract
- X-chromosomal markers in forensic genetics have become more widely used during the recent years, particularly for relationship testing. Linkage and linkage disequilibrium (LD) must typically be accounted for when using close X-chromosomal markers. Thus, when producing the weight-of-evidence, given by a DNA-analysis with markers that are linked, the normally used product rule is invalid. Here we present an efficient model for calculating likelihood ratio (LR) with markers on the X-chromosome which are linked and in LD. Furthermore, the model was applied on several cases based on data from the eight X-chromosomal loci included in the Mentype® Argus X-8 (Biotype). Using a simulation approach we showed that the use of X-chromosome data can offer valuable information for choosing between the alternatives in each of the cases we studied, and that the LR can be high in several cases. We demonstrated that when linkage and LD were disregarded, as opposed to taken into account, the difference in calculated LR could be considerable. When these differences were large, the estimated haplotype frequencies often had a strong impact and we present a method to estimate haplotype frequencies. Our conclusion is that linkage and LD should be accounted for when using the tested set of markers, and the presented model is an efficient way of doing so.
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| 40. |
- Tomas, C, et al.
(författare)
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Autosomal SNP typing of forensic samples with the GenPlex (TM) HID System: Results of a collaborative study
- 2011
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 5:5, s. 369-375
-
Tidskriftsartikel (refereegranskat)abstract
- The GenPlex (TM) HID System (Applied Biosystems - AB) offers typing of 48 of the 52 SNPforID SNPs and amelogenin. Previous studies have shown a high reproducibility of the GenPlex (TM) HID System using 250500 pg DNA of good quality. An international exercise was performed by 14 laboratories (9 in Europe and 5 in the US) in order to test the robustness and reliability of the GenPlex (TM) HID System on forensic samples. Three samples with partly degraded DNA and 10 samples with low amounts of DNA were analyzed in duplicates using various amounts of DNA. In order to compare the performance of the GenPlex (TM) HID System with the most commonly used STR kits, 500 pg of partly degraded DNA from three samples was typed by the laboratories using one or more STR kits. The median SNP typing success rate was 92.3% with 500 pg of partly degraded DNA. Three of the fourteen laboratories counted for more than two thirds of the locus dropouts. The median percentage of discrepant results was 0.2% with 500 pg degraded DNA. An increasing percentage of locus dropouts and discrepant results were observed when lower amounts of DNA were used. Different success rates were observed for the various SNPs. The rs763869 SNP was the least successful. With the exception of the MiniFiler (TM) kit (AB), GenPlex (TM) HID performed better than five other tested STR kits. When partly degraded DNA was analyzed, GenPlex (TM) HID showed a very low mean mach probability, while all STR kits except MiniFiler (TM) had very limited discriminatory power.
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| 41. |
- Winskog, Carl, et al.
(författare)
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The use of commercial alcohol products to sterilize bones prior to DNA sampling
- 2010
-
Ingår i: FORENSIC SCIENCE MEDICINE AND PATHOLOGY. - : Humana Press. - 1547-769X .- 1556-2891. ; 6:2, s. 127-129
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Tidskriftsartikel (refereegranskat)abstract
- In disaster situations it is not always possible to maintain an adequate supply of standard equipment and sterilizing solutions. We have compared bone samples from cadavers cleaned in commercial white alcohol to samples from the same individuals cleaned with 95% surgical spirit. We have found that it is possible to use a commercial, white spirit to clean specimens taken from human cadavers femoral diaphysis collected for DNA analysis.
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| 42. |
- Zackrisson, Anna-Lena, 1968-, et al.
(författare)
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Fatal intoxication cases : cytochrome P450 2D6 and 2C19 genotype distributions
- 2004
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 60:8, s. 547-552
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Many commonly used pharmaceuticals, such as antidepressants and neuroleptics as well as some illegal drugs, are metabolised by the cytochrome P450 enzyme debrisoquine 4-hydroxylase (CYP2D6). Of Caucasians, 7-10% lack this enzyme, which can, upon administration of drugs in normal therapeutic doses, lead to adverse reactions and unexpected intoxication, leading in turn even to a fatal outcome in some cases. METHODS: Individuals (n=242) who had died due to intoxication by pharmaceuticals were genotyped for CYP2D6 and CYP2C19 and compared with a reference group of 281 blood donors. A single nucleotide polymorphism (SNP) method was used to identify five CYP2D6 alleles: *1 (wt), *2, *3, *4 and *6. The allele *5, a complete gene deletion, was identified by a multiplex amplification of long DNA fragments. Four CYP2C19 alleles *1 (wt), *2, *3 and *4 were also identified by SNP analysis. RESULTS: The prevalence of the CYP2D6 poor metaboliser (PM) genotypes in individuals with fatal intoxication was lower (4.7%) than expected from the frequencies of these genotypes in the blood donors (8.5%). A significantly lower frequency P<0.005 (0.03 with correction according to Bonferroni) was found for the CYP2D6*4 allele among the fatal intoxication cases. The CYP2C19 genotype analyses showed the same results for the fatal intoxication cases and for the blood donors. CONCLUSIONS: The findings in this study confirm our earlier observations of a lower frequency of CYP2D6 PM genotypes in cases of fatal intoxication. To our knowledge, it has not been shown previously that intoxication victims might have a lower frequency of PMs than the general population.
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| 43. |
- Zackrisson, Anna-Lena, 1968-, et al.
(författare)
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High Frequency of Occurrence of CYP2D6 Gene Duplication/Multiduplication Indicating Ultrarapid Metabolism Among Suicide Cases : High frequency of CYP2D6 ultra-rapid metabolizers among suicide cases
- 2009
-
Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In Sweden about 550 individuals die every year due to intoxication with drugs. Many of these drugs are metabolized by CYP-enzymes, such as CYP2D6 and CYP2C19. Lack of these enzymes, resulting in a poor metabolism, can lead to adverse reactions, even leading to a fatal outcome. On the other hand, socalled ultra-rapid metabolism can lead to insufficient drug plasma concentration and with that failed treatment or it can lead to a high amount of active/toxic metabolites. The aim of this project was to study the genetic distributions of CYP2D6 and CYP2C19 in fatal intoxication cases (242), suicide cases (intoxications excluded) (262) and natural death cases (212). PCR followed by pyrosequencing was used for all the analyses. Surprisingly, we found an increased number of individuals carrying more than two active CYP2D6 alleles, corresponding to the phenotype of an ultra-rapid metabolizer, among the suicide cases as compared to the natural death cases (p=0.007).
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| 44. |
- Zackrisson, Anna-Lena, 1968-, et al.
(författare)
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Identification of CYP2D6 alleles by single nucleotide polymorphism analysis using pyrosequencing
- 2003
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 59:7, s. 521-526
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To develop a single nucleotide polymorphism (SNP) analysis for identification of cytochrome P450 (CYP)2D6 alleles by pyrosequencing. METHODS: Swedish blood donors ( n=282) were typed for a partial CYP2D6 genotype comprising the alleles *1 (wild type), *2 (2850C>T), *3 (2549A>del), *4 (1846G>A) and *6 (1707T>del) using polymerase chain reaction (PCR) and pyrosequencing analysis. CYP2D6*5 (CYP2D6 deleted) was identified using an established long multiplex PCR method. Pyrosequencing is a sequencing-by-synthesis method in which a cascade of enzymatic reactions yields detectable light, which is proportional to the incorporated nucleotides. One feature of typing SNPs by pyrosequencing is that each allelic variant will give a unique sequence. These variants can be readily distinguished by pattern recognition software. RESULTS: Of 281 individuals analysed, 24 (8.5%) were found to be poor metabolisers with two non-functional alleles. This is in the range of 7-10%, previously reported for Caucasians. A total of 126 individuals (45%) had one functional and one non-functional allele and 131 individuals (47%) had two functional alleles. CONCLUSION: Pyrosequencing was found to be a fast and efficient tool for genotyping. The method is robust, reliable, rapid and has high throughput.
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| 45. |
- Zackrisson, Anna-Lena, 1968-
(författare)
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Pharmacogenetics from a Forensic Perspective : CYP2D6 and CYP2C19 genotype distributions in autopsy cases
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Sweden about 550 individuals die every year due to drug intoxication. A challenge for the forensic toxicologist is to determine whether or not the analytical results can explain intoxication as a cause of death. The most common drugs found among intoxication cases are psychiatric drugs and analgesics. Many of these drugs are metabolised by CYP-enzymes such as CYP2D6 and CYP2C19. Genetic variations, polymorphisms, in the genes coding for these enzymes can lead to an inactive enzyme resulting in poor metabolism, which can lead to adverse drug reactions, even with fatal outcome. The CYP2D6 gene can be multiplied, which can lead to an ultra-rapid metabolism if the alleles are active. Another polymorphism, in the CYP2C19 gene, can also lead to an ultra-rapid metabolism. This increased metabolism can result in insufficient drug plasma concentration and, with that, failed treatment. Alternately, if the drug is a pro-drug and has to be activated by these enzymes, it can lead to a high amount of active metabolites. There is a large inter-individual variation of these polymorphisms and also a large variation between different populations. Additional information about an individual’s pharmacogenetics may possibly facilitate the interpretation of the postmortem result and contribute to solve the “toxicological puzzle”.The general aim of this thesis was to study if genetic variation in the drug metabolising enzymes, CYP2D6 and CYP2C19 can contribute to fatal intoxication. Reliable and rapid SNP and CNV assays suitable for forensic samples using PCR and pyrosequencing were developed for CYP2D6 and genotype frequencies in a Swedish population were shown to be in concordance with earlier published data. SNP assays were established for polymorphisms in the CYP2C19 gene.Genotype distributions in fatal intoxication cases were compared with Swedish blood donors and significant difference between the materials were established. The allele CYP2D6*4 was found to be less frequent among the intoxication cases, as compared with the blood donors. No differences in CYP2C19 genotype frequencies were found between the materials. These findings are the opposite of our hypothesis that we expected to find an increased number of individuals carrying genetic variations, leading to poor metabolism among fatal intoxication cases. However, we are convinced that information concerning an individual’s genotype can be of importance in specific intoxication cases. Further studies are required to illuminate this question. Two further autopsy materials were studied; suicide cases (intoxications excluded) and natural death cases. A significant increased number of individuals carrying more than two active CYP2D6 alleles among the suicide cases were found compared to natural death cases. Furthermore, we found some significant differences between the materials when the individuals in each material were grouped according to how many active CYP2D6 alleles they carry in combination with the CYP2C19 genotype, which was divided into six subgroups. We do not currently have any explanation for the differences between the materials.
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| 46. |
- Åström, Siv, 1947-
(författare)
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Long-term follow-up of pseudoexfoliation, intraocular pressure and glaucoma : epidemiological studies in northern Sweden
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Purpose An age-cohort was studied with long-term follow-up. The population was born in 1915, living in the municipality of Skellefteå in 1981. The purpose was to investigate the prevalence and incidence of pseudoexfoliation (PEX), its influence on intraocular pressure (IOP) and development of open-angle glaucoma (OAG). Another purpose was to estimate the value of screening for glaucoma by comparing the screened group within the cohort with the remaining unscreened group.Methods In 1981, 339 (40%) of the 856 individuals in the cohort underwent an eye examination. This screened group was re-examined at seven-year intervals until 2002. At each visit the presence of PEX was registered, IOP was measured and the presence of glaucoma was assessed. After the 21-year follow-up period, glaucoma cases were also searched for in the medical records of the remaining unscreened individuals in the cohort. Proportions of glaucoma were compared between the two groups.Results The prevalence of PEX was 23% (95% confidence interval (CI): 20-26%) at the age of 66 and increased to 61% (CI: 50-71%) at the age of 87. The annual incidence of PEX was 1.8% (CI: 1.3-2.4%). The prevalence of OAG increased from 2.1% (CI: 0.8-4.3%) at the age of 66 years to 25 % (CI: 16-35%) at 87 years. The overall annual incidence of OAG was 0.9% (CI: 0.6-1.3%) and for OAG with PEX 2.1% (CI: 1.2-3.3%). PEX increased the risk of developing glaucoma at least four-fold. The incidence of diagnosed OAG in women was higher in the screened group than in the unscreened group (incidence rate ratio (IRR)=1.94, p=0.035). A corresponding difference could not be verified for men (p=0.58). The mean, agedependent, increase in IOP during the 21-year observation period was 0.05 mmHg/year.Conclusion The prevalence of PEX in this study population was the highest reported, and it increased with age. The presence of PEX increased the risk of developing OAG four times. In this study a higher proportion of OAG was revealed by screening among women but not among men. The age-related IOP increase was clinically insignificant.
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