| 1. |
- Bunke, Josefine, et al.
(author)
-
Hyperspectral and Laser Speckle Contrast Imaging for Monitoring the Effect of Epinephrine in Local Anesthetics in Oculoplastic Surgery
- 2022
-
In: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 38:5, s. 462-468
-
Journal article (peer-reviewed)abstract
- PURPOSE: Epinephrine is used in local anesthetics to induce vasoconstriction and thus reduce bleeding and prolong the anesthetic effect. Finding the optimal delay between the administration of the anesthetic and skin incision to ensure vasoconstriction and minimize bleeding is important and has recently become the subject of debate. This is the first study to assess blood perfusion and oxygen saturation (sO2) simultaneously in response to a local anesthetic containing epinephrine in human oculoplastic surgery.METHODS: A local anesthetic consisting of lidocaine and epinephrine (20 mg/ml + 12.5 μg/ml) was injected in the eyelids of 9 subjects undergoing blepharoplasty. The perfusion and sO2 of the eyelids were monitored using laser speckle contrast imaging and hyperspectral imaging, respectively.RESULTS: Laser speckle contrast imaging monitoring showed a decrease in perfusion over time centrally at the site of injection. Half-maximum effect was reached after 34 seconds, and full effect after 115 seconds, determined by exponential fitting. The drop in perfusion decreased gradually further away from the injection site and hypoperfusion was less prominent 4 mm from the injection site, with a spatially dependent half-maximum effect of 231 seconds. Hyperspectral imaging showed only a slight decrease in sO2 of 11 % at the injection site.CONCLUSIONS: The optimal time delay for skin incision in oculoplastic surgery is approximately 2 minutes after the injection of lidocaine with epinephrine. Longer delay does not lead to a further decrease in perfusion. As sO2 was only slightly reduced after injection, the results indicate that the use of epinephrine is safe in the periocular region.
|
|
| 2. |
- Burkill, Sarah, et al.
(author)
-
The DQB1* 03:02 Genotype and Treatment for Pain in People With and Without Multiple Sclerosis
- 2020
-
In: Frontiers in Neurology. - : Frontiers. - 1664-2295. ; 11
-
Journal article (peer-reviewed)abstract
- Murine models have demonstrated that the major histocompatibility complex (MHC) is associated with pain-like behavior in peripheral nerve injury, however, the same association has not been shown when considering injury to the central nervous system (CNS), which more closely mimics the damage to the CNS experienced by MS patients. Previous research has indicated the DQB1*03:02 allele of the class II HLA genes as being associated with development of neuropathic pain in persons undergoing inguinal hernia surgery or with lumbar spinal disk herniation. Whether this HLA allele plays a part in susceptibility to pain, has not, as far as we are aware, been previously investigated. This study utilizes information on DQB1*03:02 alleles as part of the EIMS, GEMS, and IMSE studies in Sweden. It also uses register data for 3,877 MS patients, and 4,548 matched comparators without MS, to assess whether the DQB1*03:02 allele is associated with prescribed pain medication use, and whether associations with this genotype differ depending on MS status. Our results showed no association between the DQB1*03:02 genotype and pain medication in MS patients, with an adjusted odds ratio (OR) of 1.02 (95% CI 0.85-1.24). In contrast, there was a statistically significant association of low magnitude in individuals without MS [adjusted OR 1.18 (95% CI 1.03-1.35)], which provides support for HLA influence on susceptibility to pain in the general population. Additionally, the effect of zygosity was evident for the non-MS cohort, but not among MS patients, suggesting the DQB1*03:02 allele effect is modified by the presence of MS.
|
|
| 3. |
- Engdahl, Elin, et al.
(author)
-
Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis
- 2019
-
In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 10
-
Journal article (peer-reviewed)abstract
- Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10-22), and increased risk of future MS (OR = 2.22, p = 2 × 10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1*13:01-DQA1*01:03-DQB1*06:03 haplotype while the main association for IE1B was DRB1*13:02-DQA1*01:02-DQB1*06:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.
|
|
| 4. |
- Grut, Viktor, et al.
(author)
-
Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis : a presymptomatic case-control study
- 2021
-
In: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 28:9, s. 3072-3079
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Epstein-Barr virus (EBV) and Human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with Cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, we sought to increase the understanding of CMV in MS aetiology.METHODS: We performed a nested case-control study with presymptomatically collected blood samples identified through cross-linkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95 % confidence intervals (CI) for CMV seropositivity as risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating attributable proportion due to interaction (AP).RESULTS: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56-0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06-0.61) and EBV antigen EBNA-1 (amino acid 385-420) at age 20-39 years (AP 0.37, 95% CI 0.09-0.65).CONCLUSIONS: CMV seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity.
|
|
| 5. |
- Grut, Viktor, 1980-
(author)
-
Exposures associated with multiple sclerosis development : presymptomatic case-control studies
- 2024
-
Doctoral thesis (other academic/artistic)abstract
- Background: Multiple sclerosis (MS) is a chronic immune-mediated disease affecting the central nervous system. The current view is that MS is caused by a complex interplay of several environmental factors, eliciting an immune reaction in genetically susceptible individuals. Most previous studies of MS aetiology were retrospective, conferring the risk of reverse causation or recall bias. Few studies have been performed on data collected before the onset of the disease. The objective of this project was to identify risk factors for MS by analysing markers of exposure in samples collected before the clinical onset of MS.Method: A series of nested case-control studies were performed by cross-linking Swedish MS registries with Swedish biobanks, thereby identifying serum or plasma samples from up to 837 cases who later developed MS. For each case, up to two matched controls were selected. The following environmental risk factors were assessed: Antibodies against herpesviruses Epstein-Barr virus (EBV), Human herpesvirus 6A (HHV-6A) and Cytomegalovirus (CMV); Free Vitamin D3 Index and Vitamin D Binding Protein (DBP); and C-reactive Protein (CRP). Early signs of neural injury were assessed by measuring the concentration of neurofilament light chain in serum (sNfL). The associations between the environmental factors and future development of MS were analysed with conditional logistic regression, calculating odds ratios (OR) with 95% confidence intervals (CI). Interactions were analysed on the multiplicative and additive scales. The temporal relation of HHV-6A serostatus and axonal injury was analysed with locally estimated scatterplot smoothing regression.Results: Serological evidence of CMV infection was associated with a lower risk of MS development (OR = 0.70, 95% CI 0.56–0.88). Antagonistic interactions were observed between serological signs of CMV, HHV-6A, and EBV infection. Antibodies against HHV-6A were associated with a higher level of sNfL. In MS cases, increasing levels of HHV-6A antibodies were detected several years before increasing sNfL. Among young individuals, high levels of Free Vitamin D3 Index were associated with a lower MS risk (OR = 0.37, 95% CI 0.15–0.91). In older individuals, high levels of DBP were associated with a lower risk of developing MS (OR = 0.36, 95% CI 0.15–0.85). Elevated levels of CRP were not associated with MS risk.Conclusions: These results strengthen the evidence for HHV-6A and EBV in MS aetiology. They also support the hypothesis that CMV infection and a high level of free Vitamin D3 during childhood and adolescence are associated with a lower risk of MS later in life.
|
|
| 6. |
- Grut, Viktor, et al.
(author)
-
Free vitamin D3 index and vitamin D-binding protein in multiple sclerosis : A presymptomatic case-control study
- 2022
-
In: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 29:8, s. 2335-2342
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: High levels of 25-hydroxyvitamin D3 (25[OH]D3 ) are associated with a lower risk for multiple sclerosis (MS). The bioavailability of 25(OH)D3 is regulated by its main plasma carrier, vitamin D-binding protein (DBP). Free 25(OH)D3 can be estimated by also measuring DBP concentration. In addition, DBP has immunomodulatory functions that may independently affect MS pathogenesis. No previous studies have assessed free 25(OH)D3 or DBP in presymptomatically collected samples. This study was undertaken to assess free 25(OH)D3 and DBP as risk factors for MS.METHODS: A nested case-control study was performed with presymptomatic serum samples identified through cross-linkage of MS registries and Swedish biobanks. Concentration of 25(OH)D3 was measured with liquid chromatography and DBP levels with sandwich immunoassay. Free 25(OH)D3 was approximated as free vitamin D3 index: (25[OH]D3 /DBP) × 103 . MS risk was analyzed by conditional logistic regression, calculating odds ratios (ORs) with 95% confidence intervals (CIs).RESULTS: Serum samples from 660 pairs of matched cases and controls were included. At <20 years of age, high levels of free vitamin D3 index were associated with a lower risk of MS (highest vs. lowest quintile: OR = 0.37, 95% CI = 0.15-0.91, p for trend across quintiles = 0.04). At age 30-39 years, high levels of DBP were associated with a lower MS risk (highest vs. lowest quintile: OR = 0.36, 95% CI = 0.15-0.85, p for trend = 0.02).CONCLUSIONS: These findings support the hypothesis that high levels of free 25(OH)D3 at a young age reduce the risk of MS later in life. They also implicate a role for DBP in MS etiology.
|
|
| 7. |
- Grut, Viktor, et al.
(author)
-
Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis
- 2024
-
In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 147:1, s. 177-185
-
Journal article (peer-reviewed)abstract
- Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A.A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI).Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis).In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases.
|
|
| 8. |
- Grut, Viktor, et al.
(author)
-
Interactions between high seroreactivity to human herpes virus 6A and Epstein–Barr virus in MS development : a presymptomatic case–control study
- 2024
-
In: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 96:2, s. 302-305
-
Journal article (peer-reviewed)abstract
- Synergistic interactions between human herpesvirus 6A (HHV-6A) and Epstein–Barr virus (EBV) are hypothesized in the etiopathogenesis of multiple sclerosis (MS). This study investigated if HHV-6A and EBV seroreactivities interact regarding the risk of developing MS. Antibodies against viral antigens were analyzed in biobank samples from 670 individuals who later developed MS and matched controls. Additive interactions were analyzed. A significant interaction between HHV-6A and EBNA-1 seroreactivities was observed in study participants above the median age of 24.9 years (attributable proportion due to interaction = 0.45). This finding supports the hypothesis that HHV-6A and EBV infections interact in MS development. ANN NEUROL 2024.
|
|
| 9. |
- Grut, Viktor, et al.
(author)
-
Systemic inflammation and risk of multiple sclerosis – A presymptomatic case-control study
- 2022
-
In: Multiple Sclerosis Journal - Experimental, Translational and Clinical. - : SAGE Publications. - 2055-2173. ; 8:4
-
Journal article (peer-reviewed)abstract
- Background: C-reactive protein (CRP) is a marker of systemic inflammation. Increased levels of CRP in young persons have been suggested to decrease the risk of multiple sclerosis (MS). Objectives: To assess CRP as a risk factor for MS. Methods: Levels of CRP were measured with a high-sensitive immunoassay in biobank samples from 837 individuals who later developed MS and 984 matched controls. The risk of developing MS was analysed by conditional logistic regression on z-scored CRP values. Results: Levels of CRP were not associated with MS risk. Conclusions: We found no association between CRP levels and risk of MS development.
|
|
| 10. |
- Hedström, Anna Karin, et al.
(author)
-
Association between exposure to combustion-related air pollution and multiple sclerosis risk
- 2023
-
In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 52:3, s. 703-714
-
Journal article (peer-reviewed)abstract
- Background: Smoking and occupational pulmonary irritants contribute to multiple sclerosis (MS) development. We aimed to study the association between ambient air pollution and MS risk and potential interaction with the human leukocyte antigen (HLA)-DRB1*15:01 allele.Methods: Exposure to combustion-related air pollution was estimated as outdoor levels of nitrogen oxides (NOx) at the participants’ residence locations, by spatially resolved dispersion modelling for the years 1990–18. Using two population-based case-control studies (6635 cases, 8880 controls), NOx levels were associated with MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models. Interaction between high NOx levels and the HLA-DRB1*15:01 allele regarding MS risk was calculated by the attributable proportion due to interaction (AP). In addition, a register study was performed comprising all MS cases in Sweden who had received their diagnosis between 1993 and 2018 (n = 22 173), with 10 controls per case randomly selected from the National Population register.Results: Residential air pollution was associated with MS risk. NOx levels (3-year average) exceeding the 90th percentile (24.6 µg/m3) were associated with an OR of 1.37 (95% CI 1.10–1.76) compared with levels below the 25th percentile (5.9 µg/m3), with a trend of increasing risk of MS with increasing levels of NOx (P <0.0001). A synergistic effect was observed between high NOx levels (exceeding the lower quartile among controls) and the HLA-DRB1*15:01 allele regarding MS risk (AP 0.26, 95% CI 0.13–0.29).Conclusions: Our findings indicate that moderate levels of combustion-related ambient air pollution may play a role in MS development.
|
|
