| 1. |
- Björkman, Kristoffer, et al.
(författare)
-
Clinical course of patients with single large-scale mtDNA deletions and childhood onset anemia
- 2022
-
Ingår i: 14th European Paediatric Neurology Society Congress, Glasgow, UK (ISBN 978-3-00-072065-9).
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To add to our knowledge of the clinical spectrum of patients with single large-scale mitochondrial DNA (mtDNA) deletion and childhood onset anemia. Methods: Retrospective collection of clinical data from medical records for patients, both living and deceased, with a single large-scale mtDNA deletion from seven mitochondrial disease centers in five countries. Statistical analysis with descriptive methods and Kaplan-Meier survival analysis. Results: Seventeen patients matching the genetic criterium and with anemia onset before six years of age. Exocrine pancreatic insufficiency was only seen in five patients in this group. Multiple organs were involved in all patients, with the most common non-hematologic ones being skeletal muscle, central nervous system, endocrine, eyes, gastrointestinal system, kidneys, hearing, liver and heart. Psychomotor retardation was seen in ten patients, hearing impairment in nine patients, failure to thrive in eight patients. Eight later developed Kearns-Sayre syndrome. Eleven patients were deceased, with a median age at death of 7.5 years. Conclusions: The classically described phenotype of patients with large-scale mtDNA deletions and early onset anemia is Pearson marrow-pancreas syndrome, characterized by sideroblastic anemia and exocrine pancreas dysfunction. Only a minority of our patients fulfill the original criteria of Pearson syndrome though. Involvement of other organs than the pancreas is more common. The clinical course vary, but multi-system impact is the rule and life-expectancy is low. Early onset anemia in patients with large-scale mtDNA deletions is most frequently not associated with exocrine pancreas dysfunction. Better knowledge of the phenotype is helpful for diagnosis and more accurate prognosis.
|
|
| 2. |
- Zetterlund, Christina, et al.
(författare)
-
The relationship between low vision and musculoskeletal complaints : a case control study between age-related macular degeneration patients and age-matched controls with normal vision
- 2009
-
Ingår i: Journal of optometry. - Barcelona : Elsevier BV. - 1989-1342 .- 1888-4296. ; 2:3, s. 127-133
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Age-related Macular Degeneration (ARMD) patients often describe complaints from neck and scapula area muscles and a decreased postural control. In clinical assessment, these complaints are considered to be due to old age.PURPOSE: This study focuses on low-vision patients with ARMD, comparing them to age-matched controls without any eye disease, in order to evaluate if the linkage between self-rated visual complaints and musculoskeletal complaints is more prominent when low vision is present.METHODS: In a cross-sectional study, 24 ARMD patients, aged 65 to 85, were compared to a group of 24 controls without visual problems having a similar age distribution. Visual acuity, the need for magnification plus other optical and visual parameters were assessed. Visual, musculoskeletal and balance/proprioceptive complaints were collected by means of a self-rating questionnaire. The Visual Functioning Questionnaire - Near Activities Subscale (VFQ–NAS) was used to evaluate visual function and related complaints.RESULTS: The correlation between visual complaints and musculoskeletal complaints yielded significant values of the correlation coefficient when performed separately within each group, as well as when calculated on the entire data set [ARMD, Spearman’s rho (ρ)=0.60, P=0.002; control group ρ=0.59, P=0.004; both groups together ρ=0.50 P<0.001]. Stepwise multiple regression analysis supported the hypothesized effect of vision (Visual complaints + Minimum readable typefaces) on musculoskeletal complaints, (r2=0.42, P<0.05). CONCLUSIONS: The results in this study support the hypothesis that a relationship exists between visual and musculoskeletal problems.
|
|
| 3. |
- Strömland, Kerstin, 1934, et al.
(författare)
-
Oculo-auriculo-vertebral spectrum: associated anomalies, functional deficits and possible developmental risk factors.
- 2007
-
Ingår i: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 143A:12, s. 1317-1325
-
Tidskriftsartikel (refereegranskat)abstract
- Swedish patients with the oculo-auriculo-vertebral (OAV) spectrum participated in a prospective multidisciplinary investigation. The aims of the study were to describe their systemic and functional defects, especially autism spectrum disorders, and to search for possible etiologic risk factors. Available medical records were studied and the mothers answered a questionnaire on history of prenatal events. A clinical examination evaluating systemic findings, vision, hearing, speech, oral and swallowing function, and neuropsychiatric function, especially autism, was made. Eighteen patients, (11 males, 7 females) aged 8 months to 17 years with OAV were studied. Most frequent systemic malformations included, ear abnormalities (100%), ocular malformations (72%), vertebral deformities (67%), cerebral anomalies (50%), and congenital heart defects (33%). Functional defects consisted of hearing impairment (83%), visual impairment (28%), both visual and hearing impairment (28%), difficulties in feeding/eating (50%), speech (53%), mental retardation (39%), and severe autistic symptoms (11%). Three children were born following assisted fertilization (two intracytoplasmatic sperm injection, one in vitro fertilization), two mothers reported early bleedings, and six (33%) mothers had smoked during pregnancy.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Crafoord, Sven, et al.
(författare)
-
Sheathotomy in complicated cases of branch retinal vein occlusion
- 2008
-
Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-3768 .- 1755-375X. ; 86:2, s. 146-150
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To report the clinical experience and results of using a microsurgical technique to decompress the arteriovenous connection in complicated branch retinal vein occlusion (BRVO) combined with haemorrhage, oedema and ischaemia.Methods: We carried out a retrospective, non-randomized, interventional case study of the surgical sheathotomy decompression procedure. We enrolled 12 patients (seven women, five men; median age 64 years) with BRVO and decreased visual acuity (VA) caused by haemorrhage, oedema and ischaemia. The mean duration of thrombosis was 7 months (2–15 months). The patients were examined for pre- and postoperative best corrected VA (BCVA), intraocular pressure (IOP) and fundus photography. Ten patients were examined with fluorescein angiography and eight with ocular coherence tomography (OCT). Postoperative progression of cataract was recorded, as were other complications. The mean follow-up time was 20 months (8–39 months).Results: Best corrected VA had improved in nine patients, was unchanged in one patient and had deteriorated in two patients at the last follow-up. Noted complications were venous haemorrhage at surgery in five patients, retinal detachment in one patient and progression of cataract in four patients.Conclusions: Microsurgical treatment with sheathotomy of BRVO is a technically feasible procedure with few complications. Postoperative increased reperfusion could explain the resolution of macular haemorrhage, oedema and ischaemia, and may improve visual function in patients with this common vascular eye disease.
|
|
| 7. |
- Malm, Eva, et al.
(författare)
-
Full-field electroretinography and marked variability in clinical phenotype of Alström syndrome
- 2008
-
Ingår i: Archives of ophthalmology (1960). - Chicago : American medical association. - 0003-9950. ; 126:1, s. 51-57
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To characterize the clinical phenotype and to study the course of disease in patients with Alström syndrome, with an emphasis on retinal function assessed with full-field electroretinography (ERG). METHODS: Three age- and sex-matched patients with Alström syndrome were selected from our retinitis pigmentosa register for repeated ophthalmologic examinations that included tests for color vision and visual fields using Goldmann perimetry and for repeated assessment of full-field ERGs. RESULTS: Electroretinography demonstrated cone-rod degeneration in all 3 patients. A concomitant impairment of color vision and visual fields was also observed as well as marked variation in retinal function and in disease severity. CONCLUSIONS: Full-field ERGs confirmed that Alström syndrome is associated with a cone-rod type of retinal degeneration. In this study, we have shown a striking variability in retinal function and disease onset and severity, which has, to our knowledge, not been described previously in Alström syndrome.
|
|
| 8. |
- Magnusson, Marie, et al.
(författare)
-
A placebo-controlled study of retinal blood flow changes by pentoxifylline and metabolites in humans
- 2006
-
Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 61:2, s. 138-147
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate the possible effects of pentoxifylline metabolites on retinal blood flow in humans. METHODS: A randomized, placebo-controlled, four-period cross-over study that was observer blinded and partly blinded for the eight participants. On one occasion a placebo was given as an intravenous (i.v.) infusion over 100 min. On the other three occasions pentoxifylline was administered as i.v. infusions over 100 min at a rate of 3 mg min(-1). Before two of the pentoxifylline infusions the subjects were pretreated with either ciprofloxacin or rifampicin. Retinal blood flow was measured by scanning laser doppler flowmetry (SLDF) in a selected area of the central temporal retina before, during and until 5 h after the end of infusion. Blood samples for concentration analyses of pentoxifyllin, R-M1, S-M1, M4 and M5 were taken serially and areas under the curves (AUCs) were calculated. Linear mixed models were used for the statistical analyses. RESULTS: Mean AUCs (ng h ml(-1)) were significantly increased for pentoxifylline (1964 vs. 1453) and S-M1 (5804 vs. 4227), but not R-M1 when pentoxifylline was co-administered with ciprofloxacin. The mean AUC for M5 was significantly reduced when subjects were pretreated with rifampicin (2041 vs. 3080). Pentoxifylline with and without pretreatment with rifampicin significantly increased retinal blood flow assessed as mean flow, pulsation (i.e. 1-systole/diastole), and diastolic flow (but not during systole), compared with placebo. The increases over placebo were more pronounced on diastolic flow, 9.7% (95% confidence interval 4.2, 15.5) than on mean flow, 4.6% (1.1, 8.3) after pentoxifylline administration. With pentoxifylline after rifampicin pretreatment the corresponding differences were 11.7% (5.8, 17.9) and 5.1% (1.4, 7.8) over placebo, respectively. After co-administration of pentoxifylline and ciprofloxacin we saw only a nonsignificant trend towards increased flow during diastole, but a significant decrease in pulsation. When AUCs for pentoxifylline and its metabolites were used as regressor variables to retinal mean flow we found that pentoxifylline, R-M1 and M5 had coefficients with a positive sign indicating that they enhanced the retinal blood flow. In contrast, S-M1 and M4 had coefficients with negative sign and thus appeared to decrease the blood flow in subjects treated with pentoxifylline. CONCLUSION: The R-M1 and M5 metabolites of pentoxifylline contributed significantly to the effects of pentoxifylline on retinal blood flow.
|
|
| 9. |
- Johansson, Björn
(författare)
-
Opacification of anterior part of hydrophilic acrylic IOL or a prelenticular inflammatory membrane?
- 2012
-
Ingår i: Journal of cataract and refractive surgery. - Philadelphia : Elsevier. - 0886-3350 .- 1873-4502. ; 38:6, s. 1115-1116
-
Tidskriftsartikel (refereegranskat)abstract
- In their recent case report, Park and Chuck1 describe the bilateral appearance of an opacification at the plane of the anterior surface of the hydrophilic acrylic Akreos MI60 intraocular lens (IOL) (Bausch & Lomb). The patient's general history of diabetes mellitus, proliferative retinopathy, and iris rubeosis explains the limited pupil dilation preventing visualization of the capsulorhexis opening in their slitlamp images.
|
|
| 10. |
- Holmström, Gerd E, et al.
(författare)
-
Ophthalmologic Outcome at 30 Months Corrected Age of a Prospective Swedish Cohort of Children Born Before 27 Weeks of Gestation The Extremely Preterm Infants in Sweden Study
- 2014
-
Ingår i: JAMA OPHTHALMOLOGY. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 132:2, s. 182-189
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Follow-up at 30 months corrected age reveals eye and visual problems in one-third of children born extremely prematurely (less than27 weeks gestation). OBJECTIVE To investigate the ophthalmologic outcome of extremely preterm children at 30 months corrected age. DESIGN, SETTING, AND PARTICIPANTS A prospective, population-based follow-up study (Extremely Preterm Infants in Sweden Study [EXPRESS]) was conducted in Sweden. The population included extremely preterm infants (less than27 weeks gestation) born in Sweden between 2004 and 2007, of whom 491 survived until age 2.5 years. Screening for retinopathy of prematurity (ROP) was performed in the neonatal period. At 30 months corrected age, an ophthalmologic assessment was performed in 411 of 491 children (83.7%). MAIN OUTCOMES AND MEASURES Visual acuity, manifest strabismus, and refractive errors were evaluated. RESULTS Visual impairment was identified in 3.1% of the children, and 1.0% were blind. Refractive errors, defined as myopia less than -3 diopters (D), hypermetropia greater than +3 D, astigmatism 2 D or more, and/or anisometropia 2 D or more, were found in 25.6% of the children, and 14.1% had manifest strabismus. There were significant associations between visual impairment and treated ROP (P = .02), cognitive disability (P less than .001), and birth weight (P = .02). Multiple regression analyses revealed significant associations between strabismus and treated ROP (P less than .001), cognitive disability (P less than .01), and cerebral palsy (P = .02). Refractive errors were significantly correlated with severity of ROP (right eye, P less than .001; left eye, P less than .01). Children who had been treated for ROP had the highest frequency (69.0%) of eye and visual abnormalities. CONCLUSIONS AND RELEVANCE One-third of the extremely prematurely born children in this study had some kind of eye or visual problems, such as visual impairment, strabismus, or major refractive error. Despite being born extremely preterm, the present cohort has a similar prevalence of blindness and visual impairment as in previous Swedish cohorts of children born less prematurely.
|
|
| 11. |
- Smirthwaite, Goldina, et al.
(författare)
-
Indication criteria for cataract extraction and gender differences in waiting time
- 2014
-
Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 92:5, s. 432-438
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to investigate national indication criteria tool for cataract extraction (NIKE), a clinical tool for establishing levels of indications for cataract surgery, in relation to gender differences in waiting times for cataract extraction (CE).Methods: Data were collected by The Swedish National Cataract Register (NCR). Eye clinics report to NCR voluntarily and on regular basis (98% coverage). Comparisons regarding gender difference in waiting times were performed between NIKE-categorized and non-NIKE-categorized patients, as well as between different indication groups within the NIKE-system. All calculations were performed in spssversion 20. Multivariate analyses were carried out using logistic regression, and single variable analyses were carried out by Student’s t-test or chi square as appropriate.Results: Gender, age, visual acuity and NIKE-categorization were associated with waiting time. Female patients had a longer waiting time to CE than male, both within and outside the NIKE-system. Gender difference in waiting time was somewhat larger among patients who had not been categorized by NIKE. In the non-NIKE-categorized group, women waited 0.20 months longer than men. In the group which was NIKE-categorized, women waited 0.18 months longer than men.Conclusions: It is reasonable to assume that prioritizing patients by means of NIKE helps to reduce the gender differences in waiting time. Gender differences in waiting time have decreased as NIKE was introduced and there may be a variety of explanations for this. However, with the chosen study design, we could not distinguish between effects related to NIKE and those due to other factors which occurred during the study period.
|
|
| 12. |
- Lagali, Neil, et al.
(författare)
-
Dendritic cell maturation in the corneal epithelium with onset of type 2 diabetes is associated with tumor necrosis factor receptor superfamily member 9
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus is characterized by a low-grade inflammation; however, mechanisms leading to this inflammation in specific tissues are not well understood. The eye can be affected by diabetes; thus, we hypothesized that inflammatory changes in the eye may parallel the inflammation that develops with diabetes. Here, we developed a non-invasive means to monitor the status of inflammatory dendritic cell (DC) subsets in the corneal epithelium as a potential biomarker for the onset of inflammation in type 2 diabetes. In an age-matched cohort of 81 individuals with normal and impaired glucose tolerance and type 2 diabetes, DCs were quantified from wide-area maps of the corneal epithelial sub-basal plexus, obtained using clinical in vivo confocal microscopy (IVCM). With the onset of diabetes, the proportion of mature, antigen-presenting DCs increased and became organized in clusters. Out of 92 plasma proteins analysed in the cohort, tumor necrosis factor receptor super family member 9 (TNFRSF9) was associated with the observed maturation of DCs from an immature to mature antigen-presenting phenotype. A low-grade ocular surface inflammation observed in this study, where resident immature dendritic cells are transformed into mature antigen-presenting cells in the corneal epithelium, is a process putatively associated with TNFRSF9 signalling and may occur early in the development of type 2 diabetes. IVCM enables this process to be monitored non-invasively in the eye.
|
|
| 13. |
- Nordanstig, Joakim, et al.
(författare)
-
Vascular Quality of Life Questionnaire-6 facilitates health-related quality of life assessment in peripheral arterial disease
- 2014
-
Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 59:3, s. 700-U492
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Most commonly used outcome measures in peripheral arterial disease (PAD) provide scarce information about achieved patient benefit. Therefore, patient-reported outcome measures have become increasingly important as complementary outcome measures. The abundance of items in most health-related quality of life instruments makes everyday clinical use difficult. This study aimed to develop a short version of the 25-item Vascular Quality of Life Questionnaire (VascuQoL-25), a PAD-specific health-related quality of life instrument. Methods: The study recruited 129 individuals with intermittent claudication and 71 with critical limb ischemia from two university hospitals. Participants were a mean age of 70 +/- 9 years, and 57% were men. All patients completed the original VascuQoL when evaluated for treatment, and 127 also completed the questionnaire 6 months after a vascular procedure. The VascuQoL-25 was reduced based on cognitive interviews and psychometric testing. The short instrument, the VascuQoL-6, was tested using item-response theory, exploring structure, precision, item fit, and targeting. A subgroup of 21 individuals with intermittent claudication was also tested correlating the results of VascuQoL-6 to the actual walking capacity, as measured using global positioning system technology. Results: On the basis of structured psychometric testing, the six most informative items were selected (VascuQoL-6) and tested vs the original VascuQoL-25. The correlation between VascuQoL-25 and VascuQoL-6 was r = 0.88 before intervention, r = 0.96 after intervention, and the difference was r = 0.91 (P < .001). The Cronbach alpha for the VascuQoL-6 was .85 before and .94 after intervention. Cognitive interviews indicated that the responders considered all six items to be relevant and comprehensible. Rasch analysis was used to reduce response options from seven (VascuQoL-25) to four (VascuQoL-6). VascuQol-6 was shown to have high precision and discriminative properties. Item fit was excellent, with both "infit" and "outfit" between 0.7 and 1.3 for all six items. The standardized response mean after intervention was 1.15, indicating good responsiveness to clinical change. VascuQoL-6 results correlated strongly (r = 0.72; P < .001) with the actual measured walking ability (n = 21). Conclusions: VascuQoL-6 is a valid and responsive instrument for the assessment of health-related quality of life in PAD. The main advantage is the compact format that offers a possibility for routine use in busy clinical settings.
|
|
| 14. |
- Pivodic, Aldina, 1978, et al.
(författare)
-
Individual Risk Prediction for Sight-Threatening Retinopathy of Prematurity Using Birth Characteristics
- 2020
-
Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 138:1, s. 21-29
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: To prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness. Objectives: To create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment. Design, Setting, and Participants: In this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models. Main Outcomes and Measures: The study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Among 7609 infants (54.6% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8%) were treated for ROP, including 142 (40.1%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks' GA showed high predictive ability for the model overall (AUC, 0.90 [95% CI, 0.89-0.92] for internal validation, 0.94 [95% CI, 0.90-0.98] for temporal validation, 0.87 [95% CI, 0.84-0.89] for US external validation, and 0.90 [95% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children's Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data. Conclusions and Relevance: This study validated an individualized prediction model for infants born at 24 to 30 weeks' GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.
|
|
| 15. |
- Anesäter, Erik, et al.
(författare)
-
The influence on wound contraction and fluid evacuation of a rigid disc inserted to protect exposed organs during negative pressure wound therapy.
- 2011
-
Ingår i: International Wound Journal. - 1742-481X. ; 8, s. 393-399
-
Tidskriftsartikel (refereegranskat)abstract
- The use of a rigid disc as a barrier between the wound bed and the wound filler during negative pressure wound therapy (NPWT) has been suggested to prevent damage to exposed organs. However, it is important to determine that the effects of NPWT, such as wound contraction and fluid removal, are maintained during treatment despite the use of a barrier. This study was performed to examine the effect of NPWT on wound contraction and fluid evacuation in the presence of a rigid disc. Peripheral wounds were created on the backs of eight pigs. The wounds were filled with foam, and rigid discs of different designs were inserted between the wound bed and the foam. Wound contraction and fluid evacuation were measured after application of continuous NPWT at -80 mmHg. Wound contraction was similar in the presence and the absence of a rigid disc (84 ± 4% and 83 ± 3%, respectively, compared with baseline). Furthermore, the rigid disc did not affect wound fluid removal compared with ordinary NPWT (e.g. after 120 seconds, 71 ± 4 ml was removed in the presence and 73 ± 3 ml was removed in the absence of a disc). This study shows that a rigid barrier may be placed under the wound filler to protect exposed structures during NPWT without affecting wound contraction and fluid removal, which are two crucial features of NPWT.
|
|
| 16. |
- Englund Johansson, Ulrica, et al.
(författare)
-
Human neural progenitor cells promote photoreceptor survival in retinal explants
- 2010
-
Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835 .- 1096-0007. ; 90:2, s. 292-299
-
Tidskriftsartikel (refereegranskat)abstract
- Different types of progenitor and stem cells have been shown to provide neuroprotection in animal models of photoreceptor degeneration. The present study was conducted to investigate whether human neural progenitor cells (HNPCs) have neuroprotective properties on retinal explants models with calpain- and caspase-3-dependent photoreceptor cell death. In the first experiments, HNPCs in a feeder layer were co-cultured for 6 days either with postnatal rd1 mouse or normal rat retinas. Retinal histological sections were used to determine outer nuclear layer (ONL) thickness, and to detect the number of photoreceptors with labeling for calpain activity, cleaved caspase-3 and TUNEL The ONL thickness of co-cultured rat and rd1 retinas was found to be almost 10% and 40% thicker, respectively, compared to controls. Cell counts of calpain activity, cleaved caspase-3 and TUNEL labeled photoreceptors in both models revealed a 30-50% decrease when co-cultured with HNPCs. The results represent significant increases of photoreceptor survival in the co-cultured retinas. In the second experiments, for an identification of putative survival factors, or a combination of them, a growth factor profile was performed on conditioned medium. The relative levels of various growth factors were analyzed by densitometric measurements of growth factor array membranes. Following growth factors were identified as most potential survival factors: granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GMCSF), insulin-like growth factor 11 (IGF-II), neurotrophic factor 3 (NT-3), placental growth factor (PIGF), transforming growth factors (TGF-beta 1 and TGF-beta 2) and vascular endothelial growth factor (VEGF-D). HNPCs protect both against calpain- and caspase-3-dependent photoreceptor cell death in the rd1 mouse and against caspase-3-dependent photoreceptor cell death in normal rat retinas in vitro. The protective effect is possibly achieved by a variety of growth factors secreted from the HNPCs. (C) 2009 Elsevier Ltd. All rights reserved.
|
|
| 17. |
- Carlsson, Stina K., 1982-
(författare)
-
Effects of adenosine and acetylcholine on the lacrimal gland
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A balanced tear film is essential for a healthy ocular surface. Insufficient tear production may result in dry eye, a common disorder in the elderly population. Dry eye causes significant discomfort in the patients and may lead to visual impairment and ocular infections. The lacrimal gland secretes water, proteins and electrolytes to the aqueous layer of the tear film. Lacrimal gland secretion is tightly regulated by e.g. neuronally released acetylcholine. The effect of acetylcholine on lacrimal gland secretion was recently found to be potentiated by adenosine. Adenosine is an important signaling molecule acting upon the adenosine receptors: A1, A2A, A2B and A3.The aim of this thesis was to study effects of adenosine and acetylcholine on intracellular signaling pathways and lacrimal gland secretion. Cholinergic stimulation of secretion was shown to be regulated by the mitogen activated protein kinase p38, a protein previously not known to be involved in exocrine secretion. p38 was activated in response to cholinergic stimulation and inhibition of p38 significantly diminished cholinergic secretion.When investigating adenosine effects, potentiation of cholinergic secretion was observed by activation of the A2B receptor in addition to the previously studied A1 receptor. An A2 receptor agonist increased cholinergic rabbit lacrimal gland protein secretion at several concentrations. The increase was inhibited by antagonism of the A2B receptor, but not the A2A receptor. When investigating the intracellular signaling pathways following adenosine and acetylcholine receptor activation, adenosine was shown to increase of cAMP levels. An additional increase in cAMP levels was observed after parallel adenosine and cholinergic receptor activation. Inhibition of Ca2+ release from the endoplasmic reticulum had inhibitory effects of cholinergic stimulation of secretion. In addition, the expression of adenosine receptors in a mouse model of autoimmune dry eye was investigated. The results showed a lymphocyte dependent upregulation of A2A receptors in diseased mice compared to controls.In conclusion, the results in this thesis provide significant contributions in the search of dry eye therapeutics through studies of adenosine and acetylcholine receptor activation.
|
|
| 18. |
- Malm, Christer, et al.
(författare)
-
Evaluation of 2-D DIGE for skeletal muscle: Protocol and repeatability
- 2008
-
Ingår i: The Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa Healthcare. - 0036-5513 .- 1502-7686. ; 68:8, s. 793-800
-
Tidskriftsartikel (refereegranskat)abstract
- Proteomic analysis has the potential to yield vast amounts of data. The available proteomic methods have been hampered by methodological errors in quantification due to large gel-to-gel variations. The inclusion of an internal standard greatly reduces this variation, and therefore the purpose of this investigation was: 1) to develop a sample preparation protocol for human skeletal muscle for two-dimensional differentiated gel electrophoresis (DIGE) and 2) to investigate the repeatability of one particular system, the Ettan™ DIGE. To test repeatability, nine aliquots from the same homogenate were labelled with three different CyDye™ dyes (Cy2, Cy3, Cy5). Samples were run on 1824 cm gels, scanned with a Typhoon™ 9410 laser scanner and analysed in the DeCyder™ software. When selecting spots appearing only in triplicate (n = 1314), the mean error was 1.7 % (SD: 10.5 %; 95 % CI: 1.1-2.4 %). When setting the significance level to 99 %, no false-positive changes in protein volume ratios were detected. In the protocol presented here, only 0.5 mg tissue was used and separation of >2500 distinct protein spots in the pH range 3-11 and MW 10-200 kDa. Changes in protein abundance of <20 % could be detected. The method is especially useful when comparing muscle proteins between different conditions; for example, healthy and diseased tissue, before and after treatment or different exercise protocols.
|
|
| 19. |
- Oohashi, T, et al.
(författare)
-
Mouse ten-m/Odz is a new family of dimeric type II transmembrane proteins expressed in many tissues
- 1999
-
Ingår i: Journal of Cell Biology. - 0021-9525. ; 145:3, s. 563-577
-
Tidskriftsartikel (refereegranskat)abstract
- The Drosophila gene ten-m/odz is the only pair rule gene identified to date which is not a transcription factor. In an attempt to analyze the structure and the function of ten-m/odz in mouse, we isolated four murine ten-m cDNAs which code for proteins of 2,700-2, 800 amino acids. All four proteins (Ten-m1-4) lack signal peptides at the NH2 terminus, but contain a short hydrophobic domain characteristic of transmembrane proteins, 300-400 amino acids after the NH2 terminus. About 200 amino acids COOH-terminal to this hydrophobic region are eight consecutive EGF-like domains. Cell transfection, biochemical, and electronmicroscopic studies suggest that Ten-m1 is a dimeric type II transmembrane protein. Expression of fusion proteins composed of the NH2-terminal and hydrophobic domain of ten-m1 attached to the alkaline phosphatase reporter gene resulted in membrane-associated staining of the alkaline phosphatase. Electronmicroscopic and electrophoretic analysis of a secreted form of the extracellular domain of Ten-m1 showed that Ten-m1 is a disulfide-linked dimer and that the dimerization is mediated by EGF-like modules 2 and 5 which contain an odd number of cysteines. Northern blot and immunohistochemical analyses revealed widespread expression of mouse ten-m genes, with most prominent expression in brain. All four ten-m genes can be expressed in variously spliced mRNA isoforms. The extracellular domain of Ten-m1 fused to an alkaline phosphatase reporter bound to specific regions in many tissues which were partially overlapping with the Ten-m1 immunostaining. Far Western assays and electronmicroscopy demonstrated that Ten-m1 can bind to itself.
|
|
| 20. |
|
|
| 21. |
- Rocha, João Victor, et al.
(författare)
-
Trends, geographical variation and factors associated with the use of anti-VEGF intravitreal injections in Portugal (2013–2018): a retrospective analysis of administrative data
- 2022
-
Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- Aims The arrival of anti-vascular endothelial growth factor (anti-VEGF) therapies represented a treatment shift for several ophthalmological disorders and led to an increasing number of patients undergoing intravitreal injections. The aims of this observational study were to assess the expansion of anti-VEGF intravitreal injections in the Portuguese National Health System (NHS) and to identify factors correlated with geographical variations in episode rates.Methods Administrative database on discharge from Portuguese NHS hospitals was analysed for annual values and rates of intravitreal anti-VEGF injections at a national and regional level, between 2013 and 2018.Results The number of episodes of anti-VEGF treatment and patients treated increased 16% and 9% per year, respectively, between 2013 and 2018. During the study period around 72% of patients were treated in the Metropolitan areas of Lisbon and Porto and in the Central region. Intravitreal anti-VEGF treatment rates in 2018 were 560 per 100 000 population and presented high variability between municipalities. Higher anti-VEGF treatment rates at the municipality level were associated with shorter distances between their residence and the hospital. At the hospital level, higher ratio of ophthalmologists and higher organisational level were associated with higher anti-VEGF treatment rates.Conclusion The number of episodes and patients treated with anti-VEGF injections has been growing in recent years. Proximity to healthcare, more access to ophthalmologists and hospitals with higher organisational levels are associated with higher anti-VEGF treatment rates. Improving access is crucial to reduce regional discrepancies and ensure optimal treatment frequency, which may improve health outcomes.
|
|
| 22. |
- Ferreira, Marisa Borges, et al.
(författare)
-
Relationships between neuropsychological and antisaccade measures in multiple sclerosis patients
- 2018
-
Ingår i: PeerJ. - : PeerJ, Inc. - 2167-8359. ; 6, s. 1-18
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Stroop test is frequently used to assess deficits in inhibitory control in people with multiple sclerosis (MS). This test has limitations and antisaccade eye movements, that also measure inhibitory control, may be an alternative to Stroop.ObjectivesThe aim of this study was twofold: (i) to investigate if the performance in the antisaccade task is altered in patients with MS and (ii) to investigate the correlation between performances in neuropsychological tests, the Stroop test and the antisaccade task.MethodsWe measured antisaccades (AS) parameters with an infrared eye tracker (SMIRED 250 Hz) using a standard AS paradigm. A total of 38 subjects diagnosed with MS and 38 age and gender matched controls participated in this study. Neuropsychological measures were obtained from the MS group.ResultsPatients with MS have higher error rates and prolonged latency than controls in the antisaccade task. There was a consistent association between the Stroop performance and AS latency. Stroop performance but not AS latency was associated with other neuropsychological measures in which the MS group showed deficits.ConclusionsOur findings suggest that AS may be a selective and independent measure to investigate inhibitory control in patients with MS. More studies are necessary to confirm our results and to describe brain correlates associated with impaired performance in the antisaccade task in people diagnosed with MS.
|
|
| 23. |
- Jacobson, Lena, et al.
(författare)
-
Retinal ganglion cell topography predicts visual field function in spastic cerebral palsy
- 2020
-
Ingår i: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 62:9, s. 1100-1106
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the use of optical coherence tomography (OCT) to identify and assess visual field defects caused by primary damage to the optic radiation in individuals with spastic cerebral palsy (CP). Ten individuals with spastic CP (six females, four males, with a median age of 21 years [range 17–38y]) had their brain lesions documented with conventional magnetic resonance imaging (MRI) and diffusion-weighted MRI fibre tractography. Their macular ganglion cell layer (GCL) and inner plexiform layer (IPL) were examined with OCT and their visual fields were plotted. All participants had good visual acuity and were able to cooperate with the MRI and OCT examinations, as well as undergoing reliable perimetry. We found focal thinning of the GCL+IPL and corresponding homonymous visual field defects in individuals with brain damage affecting the optic radiation. We used GCL+IPL sector asymmetry as a sensitive OCT parameter to identify focal visual field defects. We observed no such sector asymmetry in GCL+IPL, or focal visual field defects, in individuals with normal MRI optic radiation imaging. Lesions affecting the optic radiation cause retrograde trans-synaptic degeneration of retinal ganglion cells. OCT examination of the GCL in the macula identified corresponding focal damage to the optic radiation in individuals with spastic CP and can be used to predict focal visual field defects. What this paper adds: Spastic cerebral palsy (CP) may be associated with damage to the optic radiation. Damage to the optic radiation causes retrograde trans-synaptic degeneration (RTSD). RTSD can be mapped using optical coherence tomography. Ganglion cell topography can predict visual field defects in individuals with spastic CP.
|
|
| 24. |
- Lima Ramos, Pedro, et al.
(författare)
-
Predicting participation of people with impaired vision in epidemiological studies
- 2018
-
Ingår i: BMC Ophthalmology. - : BioMed Central (BMC). - 1471-2415. ; 18, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The characteristics of the target group and the design of an epidemiologic study, in particular the recruiting methods, can influence participation. People with vision impairment have unique characteristics because those invited are often elderly and totally or partially dependent on help to complete daily activities such as travelling to study sites. Therefore, participation of people with impaired vision in studies is less predictable than predicting participation for the general population. Methods: Participants were recruited in the context of a study of prevalence and costs of visual impairment in Portugal (PCVIP-study). Participants were recruited from 4 Portuguese public hospitals. Inclusion criteria were: acuity in the better eye from 0.5 decimal (0.30logMAR) or worse and/or visual field of less than 20 degrees. Recruitment involved sending invitation letters and follow-up phone calls. A multiple logistic regression model was used to assess determinants of participation. The J48 classifier, chi-square and Fisher's exact tests were applied to investigate the possible differences between subjects in our sample. Results: Individual cases were divided into 3 groups: immediate, late and non-participants. A participation rate of 20% was obtained (15% immediate, 5% late). Factors positively associated with participation included years of education, annual hospital attendance, and intermediate visual acuity. Females and greater distance to the hospital were inversely associated with participation. Conclusion: In our study, a letter followed by a phone call was efficient to recruit a significant number of participants from a larger group of people with impaired vision. However, the improvement in participation observed after the phone call might not be cost-effective. People with low levels of education and women were more difficult to recruit. These findings need to be considered to avoid studies whose results are biased by gender or socioeconomic inequalities of their participants. Young subjects and those at intermediate stages of vision impairment, or equivalent conditions, may need more persuasion than other profiles.
|
|
| 25. |
- Makdoumi, Karim, 1977-, et al.
(författare)
-
Vasoproliferative retinal tumours in a Swedish population
- 2011
-
Ingår i: Acta Ophthalmologica. - : Wiley-Blackwell Publishing Inc.. - 1755-375X .- 1755-3768. ; 89:1, s. 91-94
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the clinical appearance and the visual outcome of a cohort of patients with vasoproliferative retinal tumours (VPRTs) that were diagnosed and treated between 2002 and 2007 at the University Hospital of Orebro.Methods: Nine patients with diagnosed VPRTs were included in a retrospective study. The mean age at the time of diagnosis was 50.2 years (range 7-74 years). Follow-up time ranged between 14 and 83 months (mean 42.6). Nine out of ten eyes received cryotherapy; six eyes were also treated with photocoagulation. One patient was treated with intravitreal injections of ranibizumab (Lucentis((R))) and another was referred for brachytherapy. Because of persisting macular oedema, one eye was treated with intravitreal injection of triamcinolon.Results: Of the treated eyes, one had anterior uveitis, six had macular oedema at baseline and four had an exudative retinal detachment at the time of diagnosis. Seven eyes underwent vitrectomy because of epiretinal membranes. Visual acuity at diagnosis was 0.21 (mean) (range 0.02-0.6) and at latest check-up 0.30 (mean) (range light perception (LP)-1.0), with improvement in six eyes and deterioration in two. Two out of four patients with retinal detachment were successfully treated surgically.Conclusion: VPRTs are benign intraretinal changes. Several complications are associated with this condition. All patients in this study had symptom-giving tumours and six patients (six eyes) already had profound macular oedema at presentation. In these cases, when complications have already developed, the final visual prognosis is poor, thereby making it important to detect these tumours early. The patient who received anti-vascular endothelial growth factor (VEGF; Lucentis) therapy showed a slow improvement and distinct regression in exudations during the follow-up time. However, no increase in visual acuity was seen. At latest examination a peripheral exudative retinal detachment was still observed. Whether anti-VEGF treatment is effective, as either an alternative or complementary therapy, must be established in the future.
|
|
