| 1. |
- Bayadsi, Haytham, 1987-, et al.
(författare)
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The correlation between small papillary thyroid cancers and gamma radionuclides Cs-137, Th-232, U-238 and K-40 using spatially-explicit, register-based methods
- 2023
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Ingår i: Spatial and Spatio-Temporal Epidemiology. - : Elsevier. - 1877-5845 .- 1877-5853. ; 47
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Tidskriftsartikel (refereegranskat)abstract
- A steep increase of small papillary thyroid cancers (sPTCs) has been observed globally. A major risk factor for developing PTC is ionizing radiation. The aim of this study is to investigate the spatial distribution of sPTC in Sweden and the extent to which prevalence is correlated to gamma radiation levels (Caesium-137 (Cs-137), Thorium-232 (Th-232), Uranium-238 (U-238) and Potassium-40 (K-40)) using multiple geospatial and geo-statistical methods. The prevalence of metastatic sPTC was associated with significantly higher levels of Gamma radiation from Th-232, U-238 and K-40. The association is, however, inconsistent and the prevalence is higher in densely populated areas. The results clearly indicate that sPTC has causative factors that are neither evenly distributed among the population, nor geographically, calling for further studies with bigger cohorts. Environ-mental factors are believed to play a major role in the pathogenesis of the disease.
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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. |
- Ostman, Maria, et al.
(författare)
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Novel Calcium Phosphate Promotes Interbody Bony Fusion in a Porcine Anterior Cervical Discectomy and Fusion Model
- 2024
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Ingår i: Spine. - : Wolters Kluwer. - 0362-2436 .- 1528-1159. ; 49:17, s. 1179-1186
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Tidskriftsartikel (refereegranskat)abstract
- Study Design: Experimental porcine anterior cervical discectomy and fusion (ACDF) model: a proof-of-concept study.Objective.The effect of monetite synthetic bone graft (SBG) containing calcium pyrophosphate and beta-tricalcium phosphate on cervical spinal fusion in a noninstrumented two-level large animal model.Summary of Background Data: ACDF is the gold standard surgical technique for the treatment of degenerative cervical spinal diseases. However, pseudarthrosis associated with increased patient morbidity occurs in similar to 2.6% of the surgeries. SBG may enhance bony fusion and subsequently decrease the risk of pseudarthrosis. Recent studies on monetite-based SBGs for use in large cranial defects in humans have shown promising bone healing results, necessitating further investigation of their use in cervical spinal fusion.Materials and Methods: Four adult female Danish G & ouml;ttingen minipigs received partial cervical anterior discectomy and intervertebral defects at an upper and lower level. One defect was filled with SBG, and the other was left empty. Bony fusion was evaluated using computed tomography (CT) at three-month intervals for 12 months. Fifteen months postsurgery, the animals were euthanized for further ex vivo qualitative histopathologic and micro-CT evaluations. Fusion rates were compared using the Fisher exact test at each time point.Results.Increased interbody bony fusion rates were observed at SBG levels (4/4) compared with control levels (0/4) evaluated by CT at 6 and 9 months postsurgery (P=0.029). Fusion was observed at all SBG levels 12 months postsurgery and at only one control level. Histopathologic evaluation confirmed high-quality interbody bony fusion at all SBG levels and fusion by spondylosis at one control level.Conclusion: This proof-of-concept study provides preliminary evidence of a novel, calcium pyrophosphate-containing, and beta-tricalcium phosphate-containing monetite SBG that promotes bony fusion compared with a negative control in a clinically relevant porcine model of ACDF.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- Hedenqvist, Patricia, et al.
(författare)
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The effect of housing environment on bone healing in a critical radius defect in New Zealand White rabbits
- 2020
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- In animal studies on bone healing, the effect of housing space and physical activity are seldom taken into account. Bone formation was evaluated in New Zealand White rabbits (mean ± SEM BW: 3.9 ± 0.11 kg) with a critical bone defect after 12 weeks of rehabilitation in pair-housing in 3 m2 large floor pens (Floor, n = 10) or standard single housing in 0.43 m2 cages (Cage, n = 10). In the randomised full-factorial study, a bone replica of calcium phosphate cement (CPC, n = 10) or autologous bone (AB, n = 10) was implanted in the unilateral 20 mm radius defect. Post-mortem, the oxidative capacity was measured by citrate synthase (CS) activity in M. quadriceps and the defect filling volume and density evaluated by microcomputer tomography (μ-CT). Histology sections were evaluated by subjective scoring and histomorphometry. Fourteen rabbits remained until the end of the study. Group Floor (n = 7; 3 CPC + 4 AB) had a higher CS activity and a larger bone defect filling volume and lower density by μ-CT measurements than group Cage (n = 7; 3 CPC + 4 AB). Three out of four rabbits in AB-Floor presented fusion of the defect with reorganisation of trabecular bone, whereas three of four in AB-Cage showed areas of incomplete healing. Floor rabbits had a higher score of bony fusion between the radius and ulna than Cage rabbits. There were no differences between groups in histomorphometry. The study found that a larger housing space increased physical activity and promoted bone formation. © 2020 Hedenqvist et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 8. |
- Mellgren, Torbjörn, 1986-, et al.
(författare)
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Guided bone tissue regeneration using a hollow calcium phosphate based implant in a critical size rabbit radius defect
- 2021
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Ingår i: Biomedical Materials. - : Institute of Physics Publishing (IOPP). - 1748-6041 .- 1748-605X. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Long bone fractures are common and sometimes difficult to treat. Autologous bone (AB), bovine bone and calcium phosphates are used to stimulate bone growth with varying results. In the present study, a calcium phosphate cement (CPC) that previously showed promising grafting capabilities was evaluated for the first time in a long bone defect. A radius defect of 20 mm was created in 20 rabbits. The defect was filled by either a hollow CPC implant that had been manufactured as a replica of a rabbit radius through indirect 3D printing, or by particulate AB as control. Defect filling and bone formation was evaluated after 12 weeks by combining micro computed tomography (mu CT) and scoring of 3D images, together with histomorphometry and histology. The mu CT and histomorphometric evaluations showed a similar amount of filling of the defect (combining graft and bone) between the CPC and AB group, but the scoring of 3D images showed that the filling in the CPC group was significantly larger. Histologically the AB graft could not be distinguished from the new bone. The AB treated defects were found to be composed of more bone than the CPC group, including reorganised cancellous and cortical bone. Both the CPC and AB material was associated with new bone formation, also in the middle of the defect, which could result in closing of the otherwise critically sized gap. This study shows the potential for an indirectly 3D printed implant in guided bone regeneration in critically sized long bone defects.
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| 9. |
- Öhnstedt, Emelie, et al.
(författare)
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Engineered bacteria to accelerate wound healing : an adaptive, randomised, double-blind, placebo-controlled, first-in-human phase 1 trial
- 2023
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Ingår i: eClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 60
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Tidskriftsartikel (refereegranskat)abstract
- Background: Impaired wound healing is a growing medical problem and very few approved drugs with documented clinical efficacy are available. CXCL12-expressing lactic acid bacteria, Limosilaoocillus reuteri (ILP100-Topical), has been demonstrated to accelerate wound healing in controlled preclinical models. In this first-in-human study, the primary objective was to determine safety and tolerability of the drug candidate ILP100-Topical, while secondary objectives included assessments of clinical and biologic effects on wound healing by traditionally accepted methods and explorative and traceable assessments.Methods: SITU-SAFE is an adaptive, randomised, double-blind, placebo-controlled, first-in-human phase 1 trial (EudraCT 2019-000680-24) consisting of a single (SAD) and a multiple ascending dose (MAD) part of three dose cohorts each. The study was performed at the Phase 1 Unit, Uppsala University Hospital, Uppsala, Sweden. Data in this article were collected between Sep 20th, 2019 and Oct 20th 2021. In total 240 wounds were induced on the upper arms in 36 healthy volunteers. SAD: 12 participants, 4 wounds (2/arm), MAD: 24 participants, 8 wounds (4/arm). Wounds in each participant were randomised to treatment with placebo/saline or ILP100-Topical.Findings: In all individuals and doses, ILP100-Topical was safe and well-tolerated with no systemic exposure. A combined cohort analysis showed a significantly larger proportion of healed wounds (p = 0.020) on Day 32 by multi-dosing of ILP100-Topical when compared to saline/placebo (76% (73/96) and 59% (57/96) healed wounds, respectively). In addition, time to first registered healing was shortened by 6 days on average, and by 10 days at highest dose. ILP100-Topical increased the density of CXCL12+ cells in the wounds and local wound blood perfusion.Interpretation: The favourable safety profile and observed effects on wound healing support continued clinical development of ILP100-Topical for the treatment of complicated wounds in patients.
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| 10. |
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