| 1. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 2. |
- Höglund, Odd, et al.
(författare)
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Chromogranin A and cortisol at intraoperative repeated noxious stimuli : surgical stress in a dog model
- 2015
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Ingår i: SAGE Open Medicine. - : SAGE Publications. - 2050-3121. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Biomarkers representing sympathetic tone and the surgical stress response are measured to objectively evaluate surgical techniques and anaesthetic protocols. If a part of the intraoperative procedure is repeated on the contralateral organ, one animal may potentially serve as its own control and, if so, may minimize the problem of individual differences of the stress response to anaesthesia and surgery. This study aimed to investigate the use of chromogranin A for measurement of the intraoperative sympathetic tone. Additional aims were to investigate chromogranin A and cortisol as indicators of the intraoperative surgical stress response caused by repeated noxious stimuli in dogs subjected to ovariohysterectomy and thereby to investigate the possibility of one dog serving as its own control. Methods: Experiments were carried out on 10 dogs subjected to ovariohysterectomy. Perioperative blood samples (0-6) were collected after premedication, immediately before induction of anaesthesia (0), after induction of anaesthesia and before incision (1), before (2) and after (3) removal of the first ovary, after a 15-min pause before removal of the second ovary (4), after removal of the second ovary (5) and after closing the abdomen (6). Plasma chromogranin A and cortisol were analysed. Results: Plasma chromogranin A did not change. Plasma cortisol concentration did not change between before anaesthesia and opening of the abdomen. Plasma cortisol increased at removal of the first ovary. Cortisol did not change at removal of the second ovary but remained increased compared to initial sample. Conclusion: The results suggest chromogranin A is a poor indicator of intraoperative sympathetic tone during elective surgery in dogs. Cortisol measurement was useful for assessment of intraoperative noxious stimuli. However, at these test conditions, neither plasma chromogranin A nor plasma cortisol was useful for assessment of repeated intraoperative noxious stimuli where one dog served as its own control..
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| 3. |
- Höglund, Odd, et al.
(författare)
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Blood pressure and heart rate during ovariohysterectomy in pyometra and control dogs: a preliminary investigation
- 2016
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surgery causes a stress response, a physiologic response to trauma. The intraoperative surgical stress response in dogs diagnosed with pyometra has not previously been described. The aim of this study was to investigate the intraoperative surgical stress response, assessed by blood pressure and heart rate measurements, in dogs diagnosed with pyometra and healthy controls. All dogs were premedicated with acepromazine and methadone, anaesthesia was induced with propofol and maintained with isoflurane, where after the dogs were subjected to ovariohysterectomy.Results: Eight dogs diagnosed with pyometra and eight healthy controls were used. Systolic blood pressure and heart rate were measured to assess the surgical stress response. Additionally propofol dosage at induction of anaesthesia and the end-tidal isoflurane concentration were investigated. The surgery was split into four phases. Phase 0 was the period 10 min before the skin incision, phase 1 was skin incision and opening of abdomen, phase 2 was manipulation of uterine horns, lifting of the ovary with stretching of the mesovarium, ligation and transection of mesovarium and phase 3 was ligation and transection of cervix, removal of organs and closing of the abdomen. Dosage of propofol at induction of anaesthesia was 3.6 +/- 1 mg/kg in dogs with pyometra and 4.1 +/- 1 in healthy controls (P = 0.37). In both groups, systolic blood pressure increased between phase 1 and 2, from 87 +/- 15 to 114 19 mmHg in dogs with pyometra, and from 88 +/- 18 to 106 +/- 20 mmHg in healthy controls, (both P < 0.0001). Systolic blood pressure did not differ significantly between groups in any of the phases. Heart rate and end-tidal concentration of isoflurane did not differ significantly between phases or between groups.Conclusions: The increased blood pressure at removal of ovaries during ovariohysterectomy suggests a pronounced noxious stimulus at this part of the procedure. In principle, the study parameters and response to surgery did not differ significantly between dogs with pyometra and healthy controls.
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| 4. |
- Landberg, Rikard, 1981, et al.
(författare)
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New alkylresorcinol metabolites in spot urine as biomarkers of whole grain wheat and rye intake in a Swedish middle-aged population
- 2018
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 72:10, s. 1439-1446
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Tidskriftsartikel (refereegranskat)abstract
- Background/objectives: Studies on the health effects of whole grains typically use self-reported intakes which are prone to large measurement errors. Dietary biomarkers that can provide an objective measure of intake are needed. New alkylresorcinol (AR) metabolites (3,5-dihydroxycinnamic acid (DHCA), 2-(3,5-dihydroxybenzamido)acetic acid (DHBA-glycine) and 5-(3,5-dihydroxyphenyl) pentanoic acid (DHPPTA)) in 24 h urine samples have been suggested as biomarkers for whole grain (WG) wheat and rye intake but remain to be evaluated in spot urine samples. Subjects/methods: The reproducibility of the new AR metabolites (DHCA, DHBA-glycine and DHPPTA) was investigated in 4 repeated samples over a period of 2 wk in spot urine from 40 Swedish men and women enroled in the SCAPIS-study, after adjustment of creatinine. Metabolite concentrations were correlated with total whole grain intake estimated during the same period. Results: The medium-term reproducibility determined for DHCA, DHPPTA and DHBA-glycine varied from moderate to excellent (intra-class correlation coefficient = 0.35–0.67). Moreover, DHCA and DHBA-glycine were independently associated with self-reported total WG intake (β = 0.18, P = 0.08 and β = 0.18, P = 0.02, respectively) and all metabolites except for DHPPA were higher among women. Conclusions: This study supports the idea of using AR metabolites in one or several spot urine samples as biomarkers of whole grain intake. These findings need to be confirmed in different populations.
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| 5. |
- Peura, Sari, et al.
(författare)
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Normal values for calprotectin in stool samples of infants from the population-based longitudinal born into life study
- 2018
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - Stockholm : Taylor & Francis Group. - 0036-5513 .- 1502-7686. ; 78:1-2, s. 120-124
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Tidskriftsartikel (refereegranskat)abstract
- Faecal calprotectin is a protein used as a diagnostic marker for inflammatory bowel diseases. We determined upper limits for normal calprotectin values for neonatal, 6, 12 and 24 months old children using a turbidimetric immunoassay in a cohort of Swedish children. The advantage of the method is that opposite to previously used enzyme-linked immunosorbent assay (ELISA) method, it enables measuring single samples, and thus, shortens the analysis time significantly. There were 72 samples (41.7% female) collected neonatally, 63 samples (34.9% female) at 6 months, 60 samples (40.0% female) at 12 months and 51 samples (43.1% female) at 24 months. The upper limits for normal values were 233, 615, 136 and 57 µg mg-1 for infants aged 0, 6, 12 and 24 months, respectively.
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| 6. |
- Buratovic, Sonja, 1986-, et al.
(författare)
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Effects on adult cognitive function after neonatal exposure to clinically relevant doses of ionising radiation and ketamine in mice
- 2018
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Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 120:3, s. 546-554
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radiological methods for screening, diagnostics and therapy are frequently used in healthcare. In infants and children, anaesthesia/sedation is often used in these situations to relieve the patients' perception of stress or pain. Both ionising radiation (IR) and ketamine have been shown to induce developmental neurotoxic effects and this study aimed to identify the combined effects of these in a murine model. Methods: Male mice were exposed to a single dose of ketamine (7.5 mg kg(-1) body weight) s.c. on postnatal day 10. One hour after ketamine exposure, mice were whole body irradiated with 50-200 mGy gamma radiation (Cs-137). Behavioural observations were performed at 2, 4 and 5 months of age. At 6 months of age, cerebral cortex and hippocampus tissue were analysed for neuroprotein levels. Results: Animals co-exposed to IR and ketamine displayed significant (P <= 0.01) lack of habituation in the spontaneous behaviour test, when compared with controls and single agent exposed mice. In the Morris Water Maze test, co-exposed animals showed significant (P <= 0.05) impaired learning and memory capacity in both the spatial acquisition task and the relearning test compared with controls and single agent exposed mice. Furthermore, in co-exposed mice a significantly (P <= 0.05) elevated level of tau protein in cerebral cortex was observed. Single agent exposure did not cause any significant effects on the investigated endpoints. Conclusion: Co-exposure to IR and ketamine can aggravate developmental neurotoxic effects at doses where the single agent exposure does not impact on the measured variables. These findings show that estimation of risk after paediatric low-dose IR exposure, based upon radiation dose alone, may underestimate the consequences for this vulnerable population.
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| 7. |
- Eriksson, Olle, 1954-, et al.
(författare)
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Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms.
- 2016
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls.Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women.Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single "whole brain".There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual-follicular) correlated with changes in self ratings of 'irritability' for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (premenstrual-follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (rs = -0.635; 0.027). The control group showed no such correlation.Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral prefrontal cortices was found to strongly correlate to premenstrual irritability. A causal relationship here seems plausible, and the findings give further support to an underlying frontal brain disturbance in hormonally influenced serotonergic activity in women with PMD. Because of the small number of subjects in the study, these results should be considered preliminary, requiring verification in larger studies.
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| 8. |
- Höglund, Odd, et al.
(författare)
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Online dosimetri för temoporfin-medierad interstitiell fotodynamisk terapi av prostata på hund
- 2012
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Ingår i: SUF-nytt. - 2001-3981. ; , s. 34-34
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Annan publikation (refereegranskat)abstract
- Bakgrund: Prostatacancer är vanligt förekommande hos män och orsakar fler dödsfall än andra cancerformer, förutom lungcancer. Ca 1 av 6 män får diagnosen prostatacancer under sin livstid (1, 2). Eftersom kirurgisk behandling och strålning av prostatavävnad orsakar biverkningar, framförallt impotens och inkontinens söks alternativa behandlingsmetoder. Interstitiell fotodynamisk terapi (PDT) är ett alternativ till att behandla tumöromvandlad prostatavävnad. Vid PDT bildas cytotoxiska radikaler som orsakar vävnadsnekros. Med hjälp av Spectracures P18-system erbjuds kontrollerad dosering av energimängden som överförs till prostatan. Syftet med denna studie var att verifiera korrelationen mellan energidos, vävnadsrespons och tröskeldos för induktion av nekros i prostata.Metod: Nio destinationsuppfödda friska beaglar användes i studien. Tre dagar före PDT gavs Temoporfin (Foscan) för fotosensibilisering. Med hjälp av transrektalt ultraljud bedömdes prostatans storlek och dosberäkning utfördes. Sju brakyterapinålar fördes in i prostatan via perineum under guidning av ultraljud och dosberäknad PDT utfördes. Sju dagar efter behandlingen avlivades hundarna.Resultat: Vid histopatologisk undersökning sågs nekroser i prostatan och förändringar i periprostata-vävnaden. En dos-responskorrelation för induktion av nekros bestämdes till 20-30 J/cm2. Online-dosimetri resulterade i mer fokuserad behandling och mindre skada på omkringliggande vävnad jämfört med PDT utan dosimetri.Konklusion: Denna studie visar att temoporfin-medierad interstitiell fotodynamisk terapi kan åstadkomma nekros av prostatavävnad. Metoden är en potentiell alternativ behandling till prostatektomi och brakyterapi.1. National Cancer Institute http://www.cancer.org/Cancer/ProstateCancer/OverviewGuide/prostate-cancer-overview-key-statistics 2. American Cancer Society 2008 Cancer Facts and Figures
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| 9. |
- Höglund, Odd, et al.
(författare)
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Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model
- 2016
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Ingår i: Journal of Biomedical Optics. - 1083-3668 .- 1560-2281. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30 J/cm(2). (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE)
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| 10. |
- Velandia, Marianne, et al.
(författare)
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Onset of Vocal Interaction Between Parents and Newborns in Skin-to-Skin Contact Immediately After Elective Cesarean Section
- 2010
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Ingår i: Birth. - : Wiley Periodicals Inc.. - 0730-7659 .- 1523-536X. ; 7:3, s. 192-201
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cesarean section is associated with delayed mother-infant interaction because neither the mother nor the father routinely maintains skin-to-skin contact with the infant after birth. The aim of the study was to explore and compare parent-newborn vocal interaction when the infant is placed in skin-to-skin contact either with the mother or the father immediately after a planned cesarean section. Methods: A total of 37 healthy infants born to primiparas were randomized to 30 minutes of skin-to-skin contact either with fathers or mothers after an initial 5 minutes of skin-to-skin contact with the mothers after birth. The newborns’ and parents’ vocal interaction were recorded on a vid-eotape and audiotape. The following variables were explored: newborns’ and parents’ soliciting, newborns’ crying and whining, and parental speech directed to the other parent and to the newborn. Results: Newborns’ soliciting increased over time (p = 0.032). Both fathers and mothers in skin-to-skin contact communicated more vocally with the newborn than did fathers (p = 0.003) and mothers (p = 0.009) without skin-to-skin contact. Fathers in skin-to-skin contact also communicated more with the mother (p = 0.046) and performed more soliciting responses than the control fathers (p = 0.010). Infants in skin-to-skin con-tact with their fathers cried significantly less than those in skin-to-skin contact with their mothers (p = 0.002) and shifted to a relaxed state earlier than in skin-to-skin contact with mothers (p = 0.029). Conclusions: Skin-to-skin contact between infants and parents immediately after planned cesarean section promotes vocal interaction. When placed in skin-to-skin contact and exposed to the parents’ speech, the infants initiated communication with soliciting calls with the parents within approximately 15 minutes after birth. These findings give reason to encourage parents to keep the newborn in skin-to-skin contact after cesarean section, to support the early onset of the first vocal communication.
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