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  • Ahrén, Maria, et al. (författare)
  • Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement
  • 2010
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:8, s. 5753-5762
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study. We report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in NI RI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3-5 nm) gadolinium oxide (DEG-Gd2O3) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy. X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd2O3 nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd2O3 nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r(1) and r(2) values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd2O3. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is. an extremely high MR signal at the cellular and molecular level.
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  • Engström, Maria, et al. (författare)
  • High Proton Relaxivity for Gadolinium Oxide Nanoparticles
  • 2006
  • Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 19:4, s. 180-186
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The objective of the present study was to investigate proton relaxation enhancement by ultrasmall (5 to 10 nm) Gd2O3 nanocrystals.Materials and methods: Gd2O3 nanocrystals were synthesized by a colloidal method and capped with diethylene glycol (DEG). The oxidation state of Gd2O3 was confirmed by X-ray photoelectron spectroscopy. Proton relaxation times were measured with a 1.5-T MRI scanner. The measurements were performed in aqueous solutions and cell culture medium (RPMI).Results: Results showed a considerable relaxivity increase for the Gd2O3–DEG particles compared to Gd-DTPA. Both T 1 and T 2 relaxivities in the presence of Gd2O3–DEG particles were approximately twice the corresponding values for Gd–DTPA in aqueous solution and even larger in RPMI. Higher signal intensity at low concentrations was predicted for the nanoparticle solutions, using experimental data to simulate a T1-weighted spin echo sequence.Conclusion: The study indicates the possibility of obtaining at least doubled relaxivity compared to Gd–DTPA using Gd2O3–DEG nanocrystals as contrast agent. The high T 1 relaxation rate at low concentrations of Gd2O3 nanoparticles is very promising for future studies of contrast agents based on gadolinium-containing nanocrystals.
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  • Fortin, Marc-André, et al. (författare)
  • Polyethylene glycol-cover ultra-small Gd2O3 nanoparticles for positive contras at 1.5 T magnetic resonance clinical scanning
  • 2007
  • Ingår i: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 18:39, s. 395501-
  • Tidskriftsartikel (refereegranskat)abstract
    • The size distribution and magnetic properties of ultra-small gadolinium oxide crystals (US-Gd2O3) were studied, and the impact of polyethylene glycol capping on the relaxivity constants (r1, r2) and signal intensity with this contrast agent was investigated. Size distribution and magnetic properties of US-Gd2O3 nanocrystals were measured with a TEM and PPMS magnetometer. For relaxation studies, diethylene glycol (DEG)-capped US-Gd2O3 nanocrystals were reacted with PEG-silane (MW 5000). Suspensions were adequately dialyzed in water to eliminate traces of Gd3+ and surfactants. The particle hydrodynamic radius was measured with dynamic light scattering (DLS) and the proton relaxation times were measured with a 1.5 T MRI scanner. Parallel studies were performed with DEG–Gd2O3 and PEG-silane–SPGO (Gd2O3,< 40 nm diameter). The small and narrow size distribution of US-Gd2O3 was confirmed with TEM (~3 nm) and DLS. PEG-silane–US-Gd2O3 relaxation parameters were twice as high as for Gd–DTPA and the r2/r1 ratio was 1.4. PEG-silane–SPGO gave low r1 relaxivities and high r2/r1 ratios, less compatible with positive contrast agent requirements. Higher r1 were obtained with PEG-silane in comparison to DEG–Gd2O3. Treatment of DEG–US-Gd2O3 with PEG-silane provides enhanced relaxivity while preventing aggregation of the oxide cores. This study confirms that PEG-covered Gd2O3 nanoparticles can be used for positively contrasted MR applications requiring stability, biocompatible coatings and nanocrystal functionalization.
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  • Hafström, Anna, et al. (författare)
  • Predictors of survival in advanced oral cancers after salvage surgery with free tissue flap reconstruction
  • 2023
  • Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 280:6, s. 2953-2964
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To identify prognostic factors for patients with advanced persistent, recurrent, or 2nd primary oral cavity squamous cell carcinoma (OCSCC) potentially unsuitable for salvage surgery with free tissue flap (FTF) reconstruction. Materials and methods: A population-based cohort of 83 consecutive patients with advanced OCSCC who underwent salvage surgery with FTF reconstruction at a tertiary referral centre between 1990 and 2017. Retrospective uni- and multivariable analyses were performed to identify factors affecting all-cause mortality (ACM), i.e., overall survival (OS), as well as disease-specific mortality (DSM), i.e., disease-specific survival (DSS) after salvage surgery. Results: Median disease-free interval until recurrence was 15 months with recurrent stage I/II in 31% and III/IV in 69%. Median age at salvage surgery was 67 years (range 31–87) and the median follow-up (alive patients) 126 months. At 2, 5, and 10 years after salvage surgery, respectively, DSS rates were 61%, 44%, and 37% and OS rates 52%, 30%, and 22%. Median DSS was 26 and OS 43 months. Multivariable analysis identified recurrent clinical regional (cN-plus) disease [HR 3.57; p <.001] and elevated gamma-glutamyl transferase (GGT) [HR 3.30; p =.003] as independent pre-salvage predictors for poor OS after salvage, whereas initial cN-plus [HR 2.07; p =.039] and recurrent cN-plus disease [HR 5.14; p <.001] predicted poor DSS. Among post-salvage factors, extranodal extension according to histopathology [HR ACM 6.11; HR DSM 9.99; p <.001] as well as positive [HR ACM 4.98; DSM 7.51; p < 0.001] and narrow surgical margins [HR ACM 2.12; DSM HR 2.80; p < 0.01] emerged as independent factors for poor survival. Conclusion: While salvage surgery with FTF reconstruction is the primary curative option for patients with advanced recurrent OCSCC, the present findings may help guide discussions with patients who have advanced recurrent regional disease and high GGT preoperatively, especially if there is a small chance of reaching surgical radicality.
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  • Hedberg, Suzanne, et al. (författare)
  • The Jejunojejunostomy: an Achilles Heel of the Roux-en-Y Gastric Bypass Construction
  • 2021
  • Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 31, s. 5141-5147
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Laparoscopic Roux-en-Y gastric bypass (RYGB) has for long been the gold standard technique in bariatric surgery, especially in the Scandinavian countries. In a tertiary hospital setting, we observed an increasing number of patients with postprandial abdominal pain and nausea, often associated with complex hypoglycemia. Objectives The present study aimed to characterize the clinical patterns, patient characteristics, and clinical outcomes after surgical revision of dysfunctional RYGB at Sahlgrenska University Hospital in Gothenburg, Sweden. Methods This cohort study included patients with RYGB who underwent revision of the jejunojejunostomy (JJ) after 2013. Information was obtained by reviewing medical records and performing complementary interviews. Results Laparoscopic revisional surgery was performed in 115 cases with either adhesiolysis or total revision of the JJ (mean age 41 years, range 19-67 years; 90% women). The median time to assessment after the last revision was 33 months (range 12-75 months). Forty-four (38%) patients reported that they were symptom-free long-term after the intervention, and 32 (28%) patients experienced an improvement in the symptoms that were the indication for revision. However, 31 (27%) patients reported no long-term improvement, and half of them (n = 16) subsequently had a reversal of the anatomy. Eight (7%) patients were lost to follow-up. Conclusions Dysfunction of the JJ appears to be a relatively common cause of postprandial pain and nausea after ante-colic/ante-gastric RYGB. Most patients with symptoms of dysfunction experienced partial or total relief following revisional surgery, but a substantial minority had persistent problems, with one in five eventually undergoing reversal of the anatomy.
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  • Klasson, Anna, 1973- (författare)
  • MRI Contrast Enhancement using Gd2O3 Nanoparticles
  • 2008
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • There is an increasing interest for nanomaterials in biomedical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3) have been investigated as a novel contrast agent for Magnetic Resonance Imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were also investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI.Results show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and a distinct increase in signal intensity in T1-mapped images. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as a multimodal contrast agent.This study shows that Gd2O3 nanoparticles possess excellent relaxation properties that are retained in more biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in for instance cell labeling experiments.
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  • Klasson, Anna, et al. (författare)
  • Positive MRI Enhancement in THP-1 Cells with Gd2O3 Nanoparticles
  • 2008
  • Ingår i: Contrast Media and Molecular Imaging. - : Wiley. - 1555-4309 .- 1555-4317. ; 3:3, s. 106-111
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a demand for more efficient and tissue-specific MRI contrast agents and recent developments involve the design of substances useful as molecular markers and magnetic tracers. In this study, nanoparticles of gadolinium oxide (Gd2O3) have been investigated for cell labeling and capacity to generate a positive contrast. THP-1, a monocytic cell line that is phagocytic, was used and results were compared with relaxivity of particles in cell culture medium (RPMI 1640). The results showed that Gd2O3-labeled cells have shorter T1 and T2 relaxation times compared with untreated cells. A prominent difference in signal intensity was observed, indicating that Gd2O3 nanoparticles can be used as a positive contrast agent for cell labeling. The r1 for cell samples was 4.1 and 3.6 s-1 mm-1 for cell culture medium. The r2 was 17.4 and 12.9 s-1 mm-1, respectively. For r1, there was no significant difference in relaxivity between particles in cells compared to particles in cell culture medium, (pr1 = 0.36), but r2 was significantly different for the two different series (pr2 = 0.02). Viability results indicate that THP-1 cells endure treatment with Gd2O3 nanoparticles for an extended period of time and it is therefore concluded that results in this study are based on viable cells.
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  • Klasson, Caritha, et al. (författare)
  • Sex Differences in the Effect of Vitamin D on Fatigue in Palliative Cancer Care : A Post Hoc Analysis of the Randomized, Controlled Trial 'Palliative-D'
  • 2022
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:3
  • Tidskriftsartikel (refereegranskat)abstract
    • In the randomized, placebo-controlled, double-blind trial 'Palliative-D', vitamin D treatment of 4000 IE/day for 12 weeks reduced opioid use and fatigue in vitamin-D-deficient cancer patients. In screening data from this trial, lower levels of vitamin D were associated with more fatigue in men but not in women. The aim of the present study was to investigate possible sex differences in the effect of vitamin D in patients with advanced cancer, with a specific focus on fatigue. A post hoc analysis of sex differences in patients completing the Palliative-D study (n = 150) was performed. Fatigue assessed with the Edmonton Symptom Assessment Scale (ESAS) was reduced in vitamin-D-treated men; -1.50 ESAS points (95%CI -2.57 to -0.43; p = 0.007) but not in women; -0.75 (95%CI -1.85 to 0.36; p = 0.18). Fatigue measured with EORTC QLQ-C15-PAL had a borderline significant effect in men (-0.33 (95%CI -0.67 to 0.03; p = 0.05)) but not in women (p = 0.55). The effect on fatigue measured with ESAS in men remained the same after adjustment for opioid doses (p = 0.01). In conclusion, the positive effect of the correction of vitamin D deficiency on fatigue may be more pronounced in men than in women. However, studies focused on analyzing sex differences in this context must be performed before firm conclusions can be drawn.
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  • Larsson, Maria, et al. (författare)
  • Omvårdnad vid cancersjukdom
  • 2021. - 3
  • Ingår i: Klinisk omvårdnad 2. - Stockholm : Liber. - 9789147113606 ; , s. 403-499
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Klinisk omvårdnad 2 är del två av en serie om två böcker. Klinisk omvårdnad del 1 och 2 tydliggör vilka konsekvenser olika sjukdomar och skador har för patienten. Hur upplever patienten att vara sjuk, hur påverkas hens grundläggande behov och vilka copingstrategier behövs? Böckerna tillhandahåller systematisk kunskap om datainsamling, de kliniska bedömningar och omvårdnadsåtgärder som behövs för att kunna tillgodose patientens grundläggande behov samt om sjuksköterskans ansvar och kompetens i sin professionsutövning. Alla kapitel har en liknande struktur, vilket gör det enkelt att orientera sig. Texterna är granskade av svenska experter och anpassade till svenska förhållanden. Böckerna vänder sig till blivande sjuksköterskor och kan användas som referens för sjuksköterskor inom olika verksamhetsområden.
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  • Mobargha, Nathalie, et al. (författare)
  • Scapular osseous free flap in head and neck reconstruction : An assessment of the postoperative function of the donor site
  • 2022
  • Ingår i: Journal of Plastic, Reconstructive and Aesthetic Surgery. - : Elsevier BV. - 1748-6815. ; 75:2, s. 753-760
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The scapular osseous free flap (SOFF) has become an important reconstructive option for complex head and neck defects. Postoperative donor site function is, however, an important consideration. The objective of this study was to prospectively investigate SOFF donor site morbidity and to relate the findings to hand dominance and neck dissection. Methods: Objective assessment included bilateral measurement of shoulder, elbow, and hand range of motion (ROM), hand strength, and distal nerve function in consecutive patients with head and neck cancer SOFF reconstruction at a tertiary referral center in Sweden between 2016 and 2019. The subjective function was assessed by the Disability of the Arm, Shoulder and Hand (DASH) questionnaire. Results: Sixteen of 20 consecutive patients were evaluated (median follow-up 10 months [range 3–17]). Significant side differences in shoulder range of motion (ROM) (flexion, abduction, external and internal rotation) were observed for patients where the SOFF had been harvested from the same side as their dominant hand (n = 9; Ps ≤ 0.04). For patients where the SOFF was harvested from the non-dominant hand side, no significant shoulder ROM side differences were observed (n = 7; Ps ≥ 0.08). There were significant side differences in shoulder ROM for patients who underwent neck dissections (n = 12; Ps ≤ 0.03), not for the other four patients. Patients reported low but varying DASH scores (median 2.5, range 0–57). Conclusion: Postoperative donor site morbidity seems to be quite acceptable after SOFF surgery. The results indicate possible benefits of choosing the non-dominant hand side for the SOFF and that a neck dissection affects postoperative shoulder outcome. Further studies are however needed.
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  • Nystedt, Björn, et al. (författare)
  • The Norway spruce genome sequence and conifer genome evolution
  • 2013
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 497:7451, s. 579-584
  • Tidskriftsartikel (refereegranskat)abstract
    • Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.
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  • Petoral, Rodrigo M, et al. (författare)
  • Synthesis and Characterization of Tb3+-Doped Gd2O3 Nanocrystals : A Bifunctional Material with Combined Fluorescent Labeling and MRI Contrast Agent Properties
  • 2009
  • Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 113:17, s. 6913-6920
  • Tidskriftsartikel (refereegranskat)abstract
    • Ultrasmall gadolinium oxide nanoparticles doped with terbium ions were synthesized by the polyol route and characterized as a potentially bifunctional material with both fluorescent and magnetic contrast agent properties. The structural, optical, and magnetic properties of the organic-acid-capped and PEGylated Gd2O3:Tb3+ nanocrystals were studied by HR-TEM, XPS, EDX, IR, PL, and SQUID. The luminescent/fluorescent property of the particles is attributable to the Tb3+ ion located on the crystal lattice of the Gd2O3 host. The paramagnetic behavior of the particles is discussed. Pilot studies investigating the capability of the nanoparticles for fluorescent labeling of living cells and as a MRI contrast agent were also performed. Cells of two cell lines (THP-1 cells and fibroblasts) were incubated with the particles, and intracellular particle distribution was visualized by confocal microscopy. The MRI relaxivity of the PEGylated nanoparticles in water at low Gd concentration was assessed showing a higher T-1 relaxation rate compared to conventional Gd-DTPA chelates and comparable to that of undoped Gd2O3 nanoparticles.
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  • Sjöberg, Sara, 1979, et al. (författare)
  • CD44-deficiency on hematopoietic cells limits T-cell number but does not protect against atherogenesis in LDL receptor-deficient mice
  • 2009
  • Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 206:2, s. 369-374
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Vascular and inflammatory cells express adhesion molecule CD44. We demonstrated previously that enhanced CD44 localizes in human atherosclerotic lesions. Apolipoprotein E/cd44 double-deficient mice and apolipoprotein E-deficient mice transplanted with CD44-deficient bone marrow (BM) exhibit reduced atherosclerosis. Since CD44 is a novel factor in atherogenesis, it is imperative that it is investigated in more than one animal model to conclusively determine its role in this particular disease pathology. To test the hypothesis that CD44 expressed by hematopoietic cells plays a critical role in atherogenesis in the low density lipoprotein (LDL) receptor-deficient mouse model, we performed BM reconstitution experiments.METHODS: Lethally irradiated LDL receptor-deficient mice were transplanted with either CD44-deficient or wild-type BM. Beginning 10 weeks after successful reconstitution, mice consumed a cholesterol-enriched atherogenic diet for 6 or 11 weeks.RESULTS: Surprisingly, CD44-deficiency on BM-derived inflammatory cells did not affect lesion size. Additionally, neither group displayed differences in smooth muscle cell, macrophage, collagen, or elastin content as well as lipoprotein levels. However, lesions in CD44-deficient BM-recipient mice contained fewer T-cells compared to wild-type BM mice. Interestingly, CD44-deficient T-cells expressed less chemokine receptor-5 mRNA. Furthermore, in vivo leukocyte adhesion decreased in CD44-deficient mice compared to wild-type mice.CONCLUSION: This study surprisingly revealed that atherogenesis does not require CD44 expression on hematopoietic cells in the LDL receptor-deficient mouse model. However, CD44 promotes T-cell recruitment, downregulates chemokine receptor-5, and participates critically in leukocyte adhesion in vivo. Consequently, the anti-atherogenic role of CD44 may require CD44-deficiency on cell types other than inflammatory cells in the LDL receptor-deficient mouse model.
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  • Söderlind, Fredrik, et al. (författare)
  • Colloidal synthesis and characterization of ultrasmall perovskite GdFeO3 nanocrystals
  • 2008
  • Ingår i: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 19:8, s. 085608-
  • Tidskriftsartikel (refereegranskat)abstract
    • Synthesis of very small (about 4 nm) perovskite structured gadolinium orthoferrite nanoparticles (GdFeO3) was performed by the polyol method. The material shows promising relaxivity properties and potential as a contrast agent in magnetic resonance imaging. The perovskite nanoparticles were characterized by x-ray diffraction, transmission electron microscopy, energy dispersive x-ray spectroscopy, Fourier transform infrared spectroscopy, magnetic resonance, and magnetization measurements. Upon heating in air at 800 °C for 3 h the size of the crystals increased to about 40 nm. The crystalline structure of the heat treated compound is in good agreement with perovskite GdFeO3 as the primary product. Contributions from various secondary phases were also identified, including one hitherto unknown phase with the suggested composition 'Gd3FeO6' and isostructural with Gd3GaO6. The novel 'Gd3FeO6' phase appears to be kinetically stabilized in the nano state.
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