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1.
  • Abdellah, Tebani, et al. (författare)
  • Integration of molecular profiles in a longitudinal wellness profiling cohort.
  • 2020
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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  • Ståhl, Patrik, Dr., et al. (författare)
  • Visualization and analysis of gene expression in tissue sections by spatial transcriptomics
  • 2016
  • Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 353:6294, s. 78-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis of the pattern of proteins or messenger RNAs (mRNAs) in histological tissue sections is a cornerstone in biomedical research and diagnostics. This typically involves the visualization of a few proteins or expressed genes at a time. We have devised a strategy, which we call "spatial transcriptomics," that allows visualization and quantitative analysis of the transcriptome with spatial resolution in individual tissue sections. By positioning histological sections on arrayed reverse transcription primers with unique positional barcodes, we demonstrate high-quality RNA-sequencing data with maintained two-dimensional positional information from the mouse brain and human breast cancer. Spatial transcriptomics provides quantitative gene expression data and visualization of the distribution of mRNAs within tissue sections and enables novel types of bioinformatics analyses, valuable in research and diagnostics.
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  • Aineskog, Helena, et al. (författare)
  • A case report of a complete degloving injury of the penile skin
  • 2016
  • Ingår i: International Journal of Surgery Case Reports. - : Elsevier BV. - 2210-2612. ; 29, s. 1-3
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Male genital degloving injuries are unusual and rarely caused by animal bite. Usually patients attend health care immediately if bitten in the genital area. Prophylactic antibiotics is routinely used (Gomes et al., 2000). A penile degloving usually begins just proximal of the coronal line and progress down to the base of the shaft. Deep erectile tissue and the spermatic cord are seldom damaged and the endogenous skin of glans usually survives (Brown and Fryer, 1957; Morey et al., 2004; Finical and Arnold, 1999).PRESENTATION OF CASE: A heavily smoking man with a previous history of bladder cancer presented himself to the emergency department 24h after a dog bite degloved his penis. The avulsed skin was necrotic and subsequently excised. Antibiotic treatment was started. A bacterial swab was found positive for canine oral flora. The skin defect was closed using a 1:1 meshed split thickness skin graft from the inner thigh. Smoking cessation was encouraged. At the three month follow up the patient expressed satisfaction with both cosmetic and functional result and was now non-smoking.DISCUSSION: Several approaches to reconstruct penile skin exist. Split thickness skin graft has been lifted as a preferable alternative (Brown and Fryer, 1957; Finical and Arnold, 1999; Paraskevas et al., 2003) [5]. In this case, the avulsed skin was necrotic and could not be used. A 1:1 meshed split-thickness graft was chosen with excellent results.CONCLUSION: 1:1mesh of the graft can be recommended for easy attachment with a good functional and esthetical result. The potential risk of losing intimacy appearance or having to go through repeated procedures in the genital area motivated smoking cessation for this patient.
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  • Asswad, Amjad Ghazal, et al. (författare)
  • Delayed, Unprovoked, Hemodynamic Collapse with Following Asystole in a Pediatric Patient Following a High-Voltage Injury : A Case Report and Literature Review
  • 2022
  • Ingår i: Pediatric Cardiology. - : Springer Nature. - 0172-0643 .- 1432-1971. ; 43:5, s. 1163-1168
  • Forskningsöversikt (refereegranskat)abstract
    • Electrical incidents are common and mostly uneventful, though can be severe and sometimes lethal. Aside from skin, muscle and soft tissue damage, electrical injuries can cause cardiac arrhythmias, the most common cardiac complication. The case of a 14-year-old girl who sustained 48.5% TBSA burns following a high-voltage electrical injury is described. She suffered five episodes of asystole 78 h following the injury, requiring extracorporeal membrane oxygenation. The cause of the delayed asystole was investigated and a PubMed literature search was conducted to explore late presenting cardiac sequelae following electrical injuries. This yielded fifteen studies, identified as relevant, of high quality and in the English language. These studies included a total of 1411 patients of whom only 3 were found to have had late potentially lethal arrhythmias, all manifesting within the first 24 h after the injury. Of these patients, 32 suffered cardiac arrests shortly after the electrical injury, 11 of which were documented as asystolic arrests though these were all from a single study with the rural locale and prolonged delay in arrival to the hospital setting contributing to this finding. To our knowledge, this is the only pediatric cardiac arrest developing in a stable patient over 72 h following the initial electrical injury. No other patient has suffered any significant cardiac complications first presenting outside the initial 24-h period following the electrical injury. Guidelines and recommendations on post electrical injury observation of patient vary and further research into this field is required to allow for guidance unification.
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  • Azzena, B, et al. (författare)
  • Late complications of high-voltage electrical injury might involve multiple systems and be related to current path
  • 2016
  • Ingår i: Annals of Burns and Fire Disasters. - 1121-1539 .- 1592-9558. ; 29:3, s. 192-194
  • Tidskriftsartikel (refereegranskat)abstract
    • SUMMARYDelayed complications of electrical burns are mostly unexpected, and the link between the injury and the symptoms oftengoes unrecognized. A possible relation between source-ground sites and late clinical manifestations was recently emphasized. We report aunique case of combined intestinal-spinal delayed complications following a high-voltage electrical injury, a possible explanation being agreater current flow through the right hemisoma. The potential for late complications is an additional feature that physicians must considerin managing electrical injuries. Manifestations are variable and presentation is confounding, but current flow path can constitute a precioussource of information to predict complications in the late phase of management.
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11.
  • Bergquist, Maria, et al. (författare)
  • Altered adrenal and gonadal steroids biosynthesis in patients with burn injury
  • 2016
  • Ingår i: Clinical Mass Spectrometry. - : Elsevier BV. - 2213-8005 .- 2376-9998. ; 1, s. 19-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Burn injury inevitably leads to changes in the endogenous production of cytokines, as well as adrenal and gonadal steroids. Previous studies have reported gender-related differences in outcome following burn injury, which suggests that gonadal steroids may play a role. The aim of this study was to assess alterations in concentration of endogenous steroids in patients with burn injury.Methods: For this single-center, prospective descriptive study, high-sensitivity liquid chromatography tandem mass spectrometry (LC-MS/MS)-based steroid quantification was used to determine longitudinal profiles of the concentrations of endogenous steroids in plasma from sixteen adult male patients with burn injury (14.5-72% of total body surface area). Steroids were extracted from plasma samples and analyzed using multiple reaction monitoring acquisition, with electrospray ionization on a triple quadruple mass spectrometer. Total protein concentration was measured in the samples using spectrophotometry.Results: Steroid and total protein concentration distributions were compared to reference intervals characteristic of healthy adult men. Concentrations of the following steroids in plasma of burn injured patients were found to correlate positively to the area of the burn injury: cortisol (r = 0.84), corticosterone (r = 0.73), 11-deoxycortisol (r = 0.72), androstenedione (r = 0.72), 17OH-progesterone (r = 0.68), 17OH-pregnenolone (r = 0.64) and pregnenolone (r = 0.77). Concentrations of testosterone decreased during the acute phase and were up to ten-times lower than reference values for healthy adult men, while concentrations of estrone were elevated. By day 21 after injury, testosterone concentrations were increased in younger, but not older, patients. The highest concentrations of estrone were observed on day 3 after the injury and then declined by day 21 to concentrations comparable to those observed on the day of the injury.Conclusion: Burn injury alters endogenous steroid biosynthesis, with decreased testosterone concentrations and elevated estrone concentrations, during the first 21 days after the injury. Concentrations of glucocorticoids, progestagens and androgen precursors correlated positively with the area of burn injury. The finding of increased estrone following burn injury needs to be confirmed in a larger hypothesis driven study.
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  • Bergquist, Maria, et al. (författare)
  • Glucocorticoid receptor expression and binding capacity in patients with burn injury.
  • 2016
  • Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 60:2, s. 213-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Burn injuries are associated with strong inflammation and risk of secondary sepsis which both may affect the function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in leucocytes from patients admitted to a tertiary burn center.
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  • Bergquist, Maria, et al. (författare)
  • The time-course of the inflammatory response to major burn injury and its relation to organ failure and outcome
  • 2019
  • Ingår i: Burns. - : Elsevier BV. - 0305-4179 .- 1879-1409. ; 45:2, s. 354-363
  • Tidskriftsartikel (refereegranskat)abstract
    • Burn injury causes major inflammatory activation and cytokine release, however, the temporal resolution of the acute and sub-acute inflammatory response has not yet been fully delineated. To this end, we have quantified 20 inflammatory mediators in plasma from 44 adult patients 0-21 days after burn injury and related the time course of these mediators to % total body surface area (TBSA) burned, clinical parameters, organ failure and outcome. Of the cytokines analyzed in these patients, interleukin 6 (IL-6), IL-8, IL-10 and monocyte chemoattractant protein 1 (MCP-1) correlated to the size of the injury at 24-48h after burn injury. In our study, the concentration of IL-10 had prognostic value in patients with burn injury both measured at admission and at 24-48h after injury. However, simple demographic data such as age, % burned TBSA, inhalation injury and their combination, the Baux score and modified Baux score, outperform most of the cytokines, with the exception of IL-8 and MCP1 levels on admission, in predicting death.
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  • Bergstrand, Sara, 1978- (författare)
  • Preventing pressure ulcers by assessment of the microcirculation in tissue exposed to pressure
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The overall aim of this thesis was to combine optical methods into a system with the ability to simultaneously measure blood flow changes at different tissue depths. The goal of such a system was to reveal vascular mechanisms relevant to pressure ulcer etiology under clinically relevant conditions and in relation to the evaluation of pressure-redistribution support surfaces.This thesis consists of four quantitative, cross-sectional studies measuring blood flow responses before, during, and after pressure exposure of the sacral tissue. Two optical methods – photoplethysmography and laser Doppler flowmetry – were combined in a newly developed system that has the ability to discriminate blood flows at different tissue depths. Studies I and II explored blood flow responses at different depths in 17 individuals. In Study I the blood flow was related to tissue thickness and tissue compression during pressure exposure of ≥ 220 mmHg. In Study II, the sacral tissue was loaded with 37.5 mmHg and 50.0 mmHg, and the variation in blood flow was measured. Studies III and IV included 42 healthy individuals < 65 years, 38 healthy individuals ≥ 65 years, and 35 patients ≥ 65 years. Study III included between-subject comparisons of blood flow and pressure between individuals in the three study groups lying in supine positions on a standard hospital mattress. Study IV added within-subject comparisons while the individual was lying on four different types of mattress. The studies explored the vascular phenomena pressure-induced vasodilation (PIV) and reactive hyperemia (RH).The most common blood flow response to tissue exposure in this thesis was PIV, although a decrease in blood flow (a lack of PIV) was observed in some individuals. The patients tended to have higher interface pressure during pressure exposure than the healthy groups but no differences in blood flow responses were seen. Our results showed that pressure levels that are normally considered to be harmless could have a significant effect on the microcirculation in different tissue structures. Differences in individual blood flow responses in terms of PIV and RH were seen, and a larger proportion of individuals lacked these responses in the deeper tissue structures compared to more superficial tissue structures.This thesis identified PIV and RH that are important vascular mechanisms for pressure ulcer development and revealed for the first time that PIV and RH are present at different depths under clinically relevant conditions. The thesis also identified a population of individuals not previously identified who lack both PIV and RH and seem to be particularly vulnerable to pressure exposure. Further, this thesis has added a new perspective to the microcirculation in pressure ulcer etiology in terms of blood flow regulation and endothelial function that are anchored in clinically relevant studies. Finally, the evaluation of pressureredistribution support surfaces in terms of mean blood flow during and after tissue exposure was shown to be unfeasible, but the assessment of PIV and RH could provide a new possibility for measuring individual physiological responses that are known to be related to pressure ulcer development.
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  • Bersani, Cinzia, et al. (författare)
  • Genome-wide identification of Wig-1 mRNA targets by RIP-Seq analysis
  • 2016
  • Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 7:2, s. 1895-1911
  • Tidskriftsartikel (refereegranskat)abstract
    • RNA-binding proteins (RBPs) play important roles in the regulation of gene expression through a variety of post-transcriptional mechanisms. The p53-induced RBP Wig-1 (Zmat3) binds RNA through its zinc finger domains and enhances stability of p53 and N-Myc mRNAs and decreases stability of FAS mRNA. To identify novel Wig-1-bound RNAs, we performed RNA-immunoprecipitation followed by high-throughput sequencing (RIP-Seq) in HCT116 and Saos-2 cells. We identified 286 Wig-1-bound mRNAs common between the two cell lines. Sequence analysis revealed that AU-rich elements (AREs) are highly enriched in the 3'UTR of these Wig-1-bound mRNAs. Network enrichment analysis showed that Wig-1 preferentially binds mRNAs involved in cell cycle regulation. Moreover, we identified a 2D Wig-1 binding motif in HIF1A mRNA. Our findings confirm that Wig-1 is an ARE-BP that regulates cell cycle-related processes and provide a novel view of how Wig-1 may bind mRNA through a putative structural motif. We also significantly extend the repertoire of Wig-1 target mRNAs. Since Wig-1 is a transcriptional target of the tumor suppressor p53, these results have implications for our understanding of p53-dependent stress responses and tumor suppression.
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  • Bodin, Maja, et al. (författare)
  • Svåra skador och dödsfall till följd av brand : En genomgång av brandskadade i Sverige 2010
  • 2012
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • En genomgång av brandskadade i Sverige 2010. Den epidemiologiska kunskapen om, och omfattningen av, personskador orsakade av eld och rök (såväl lindriga som svåra och dödliga) är otillräcklig. Målet med denna studie, som genomförts av Institutionen för Kirurgiska vetenskaper vid Uppsala universitet i samverkan med MSB, har varit att sammanställa tillgänglig data över skador som kan kopplas till en brand under 2010 och lyfta fram särskilt utsatta grupper. Detta för att skapa en epidemiologisk kunskapsbas som kan ligga till grund för preventionsarbete och vidare forskning.
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  • Boissin, Constance, et al. (författare)
  • Development and evaluation of deep learning algorithms for assessment of acute burns and the need for surgery
  • 2023
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Assessment of burn extent and depth are critical and require very specialized diagnosis. Automated image-based algorithms could assist in performing wound detection and classification. We aimed to develop two deep-learning algorithms that respectively identify burns, and classify whether they require surgery. An additional aim assessed the performances in different Fitzpatrick skin types. Annotated burn (n = 1105) and background (n = 536) images were collected. Using a commercially available platform for deep learning algorithms, two models were trained and validated on 70% of the images and tested on the remaining 30%. Accuracy was measured for each image using the percentage of wound area correctly identified and F1 scores for the wound identifier; and area under the receiver operating characteristic (AUC) curve, sensitivity, and specificity for the wound classifier. The wound identifier algorithm detected an average of 87.2% of the wound areas accurately in the test set. For the wound classifier algorithm, the AUC was 0.885. The wound identifier algorithm was more accurate in patients with darker skin types; the wound classifier was more accurate in patients with lighter skin types. To conclude, image-based algorithms can support the assessment of acute burns with relatively good accuracy although larger and different datasets are needed.
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  • Danielsson, Frida, et al. (författare)
  • Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model
  • 2013
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:17, s. 6853-6858
  • Tidskriftsartikel (refereegranskat)abstract
    • The transformation of normal cells to malignant, metastatic tumor cells is a multistep process caused by the sequential acquirement of genetic changes. To identify these changes, we compared the transcriptomes and levels and distribution of proteins in a four-stage cell model of isogenically matched normal, immortalized, transformed, and metastatic human cells, using deep transcriptome sequencing and immunofluorescence microscopy. The data show that similar to 6% (n = 1,357) of the human protein-coding genes are differentially expressed across the stages in the model. Interestingly, the majority of these genes are down-regulated, linking malignant transformation to dedifferentiation. The up-regulated genes are mainly components that control cellular proliferation, whereas the down-regulated genes consist of proteins exposed on or secreted from the cell surface. As many of the identified gene products control basic cellular functions that are defective in cancers, the data provide candidates for follow-up studies to investigate their functional roles in tumor formation. When we further compared the expression levels of four of the identified proteins in clinical cancer cohorts, similar differences were observed between benign and cancer cells, as in the cell model. This shows that this comprehensive demonstration of the molecular changes underlying malignant transformation is a relevant model to study the process of tumor formation.
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21.
  • Danielsson, Pär, et al. (författare)
  • A Novel Concept for Treating Large Necrotizing Fasciitis Wounds With Bilayer Dermal Matrix, Split-thickness Skin Grafts, and Negative Pressure Wound Therapy
  • 2009
  • Ingår i: Wounds (King of Prussia, Pa.). - 1044-7946 .- 1943-2704. ; 21:8, s. 215-220
  • Tidskriftsartikel (refereegranskat)abstract
    • Treatment of necrotizing fasciitis (NF) includes radical surgical debridement often resulting in large wounds that need to be closed with methods including split-thickness skin grafts (STSG), local flaps, or guided tissue regeneration procedures. In this case report, a 45 year-old Caucasian male was surgically treated for a benign left groin hernia, developed NF, and was transferred to the authors burn unit. The wound was treated initially with wide debridement and with a brief delay before finally closing the wound. A collagen matrix such as Integra (R) Dermal Regeneration Template (Integra LifeSciences, Plainsboro, NJ) in combination with STSG and negative pressure wound treatment, can provide fast recovery resulting in pliable, functional skin.
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22.
  • Dimander, Josefin, et al. (författare)
  • Documented nutritional therapy in relation to nutritional guidelines post burn injury : a retrospective observational study
  • 2023
  • Ingår i: Clinical Nutrition ESPEN. - : Elsevier. - 2405-4577. ; 56, s. 222-229
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & aims: Intensive nutritional therapy is an essential component of burn care. Regardingpost-minor burn injuries, the literature is lacking. The aim of this study was to evaluate documentednutritional therapy in relation to international guidelines after both minor and major burn injuries. The secondary aim of this study was to evaluate the adequacy of energy and protein intake compared toindividual nutritional goals post-burn injury.Methods: A retrospective observational single-centre study including patients admitted between 2017and 2019 at a burn centre in Sweden was performed. The patients included in the study were >18 years old and in need of hospital care for > 72 h post-burn injury. Information about patients' demographics,nutritional therapy, and clinical characteristics of burn injury was collected. The patients were dividedaccording to total body surface area burnt (TBSA %) into minor burn injuries (TBSA <20%) and major burninjuries (TBSA >20%). Descriptive statistics were used to analyse data. Adherence to guidelines wasestablished by comparing 24 nutritional therapy recommendations to documented treatment. If documented nutritional treatment were in accordance with guidelines, adherence was considered high(>80%), moderate (60-79.9%) or low (<59.9%).Results: One hundred thirty-four patients were included, 90 patients with minor burn injuries and 44patients with major burn injuries. Documented adherence to the nutritional guideline was overall low.After minor burn injury, 8% (2/24) of nutritional therapy recommendations had a high adherence (fatintake <35% of total energy intake and enteral nutrition as prioritized feeding route), 17% (4/24) amoderate adherence, and 75% (18/24) a low adherence. In patients treated after a major burn injury,there were two recommendations with documented high adherence (Vitamin C and Zinc); 25% (6/24)had moderate adherence, and 67% (16/24) had low adherence. In addition, quite a large amount ofmissing data was found.Adequacy of documented nutritional intake, compared to the individual documented goal, was 78%(±23%) for energy and 66% (±22%) for protein after minor burn injury. After major burn injury, the adequacy was 89% (±21%) for energy and 78% (±19%) for protein, respectively.Conclusions: This study revealed low adherence to nutritional guidelines in patients treated for minorand major burn injuries. Compared to major burn injuries, lower documented adequacy for both energyand proteins was found in minor burn injuries. Given the disparity between guidelines and documentednutritional therapy, and the lack of specific guidelines for minor burn injuries, there could be aconsiderable risk of inadequate nutritional therapy post-burn injury.
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  • Dimander, Josefin, et al. (författare)
  • Two Modified Questionnaires for the Assessment of Nutrition Impact Symptoms in the Rehabilitation Phase after Burn Injury : A Content Validation Study
  • 2022
  • Ingår i: European Burn Journal. - : MDPI. - 2673-1991. ; 3:1, s. 156-164
  • Tidskriftsartikel (refereegranskat)abstract
    • Disease Related Appetite Questionnaire (DRAQ) and Eating Symptom Questionnaire(ESQ) are used to assess nutrition impact symptoms, which are symptoms that can negatively affectthe patients’ food intake. However, these questionnaires have not yet been adapted to the needsof patients recovering from burn injuries. Our aim was therefore to develop DRAQ and ESQ forassessments of nutrition impact symptoms after burn injury. A content validation index (I-CVI) foritems included in DRAQ and ESQ, regarding their relevance for possible nutrition impact symptomsin a burn-injured patient (Likert scale 1–4), was performed by an expert review group. A clarityvalidation by expert and non-expert reviewers was carried out. Two of the eleven questions inDRAQ and eight of the fourteen questions in ESQ were not considered relevant and were thereforeremoved from the questionnaires. Five additional questions were added to DRAQ and two to ESQ.A high degree of consensus on relevance (scale-content validity index average, S-CVI/Ave, 0.86 forDRAQ-burn and 0.83 for ESQ-burn) was reached in the expert group. To conclude, it is suggestedthat we use developed forms of DRAQ and ESQ (DRAQ-burn and ESQ-burn) for the assessment ofnutrition impact symptoms, specifically during the rehabilitation phase of burn-injured patients.
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  • Eggert, Erik, et al. (författare)
  • Medical and biological factors affecting mortality in elderly residential fire victims : a narrative review of the literature
  • 2017
  • Ingår i: Scars, Burns & Healing. - : SAGE Publications. - 2059-5131. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • For older people (aged over 65 years), the risk of dying in a residential fire is doubled compared to the general population. Obvious causes of death mainly include smoke inhalation and burn injuries. That older people are more fragile and have more concurrent diseases is inherent, but what is it that makes them more vulnerable? It is known that the number of elderly people is increasing globally and that the increased risk of death in fires can be explained, at least in part, by physical and/or cognitive disabilities as well as socioeconomic and behavioural factors. The possibility that medical illnesses and an aging organism/tissues might explain this increased risk has not been shown to the same extent. Therefore, this narrative literature review focuses on medical and biological explanations. An initial search using the terms ‘elderly’, ‘fatal’, ‘residential’ and ‘fire’ yielded some interesting articles. Using a broader snowball search also accepting grey literature, several additional risk factors could be identified. Cardiovascular diseases, in particular atherosclerotic heart disease, greatly increases the vulnerability to, for example, carbon monoxide and probably also other asphyxiating gases. Cardiovascular diseases and lack of physical fitness may also increase vulnerability to heat. Burned elderly patients are also at a higher risk of death than younger patients, but it is controversial whether it is age itself or the pre-existing illnesses that come with age that increase the risk. Immunosenescence, malnutrition and female gender are other risk factors for poorer outcome after burns, all of which are common among older people.
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28.
  • Enblom, Sara, et al. (författare)
  • Fatigue after burn – Is it common? A preliminary survey
  • 2021
  • Ingår i: Burns Open. - : Elsevier. - 2468-9122. ; 5:3, s. 134-136
  • Tidskriftsartikel (refereegranskat)abstract
    • Physical function and daily activities are often affected after burn injury. Fatigue is a condition that is rarely assessed. Being a well-known sequela after traumatic brain-injury or diseases of the nervous system, fatigue has also been described among the burn population with a negative impact on daily activities and reduced capacity for work.The aim of this study was to examine if, and to what extent, fatigue is a problem among our burn victims.Twenty consecutive patients scheduled for follow-up at the Burn center’s outpatient clinic in Uppsala, were asked to fill out the Fatigue Severity Scale (FSS). A healthy reference group without a burn injury, gender and age matched, were asked to fill out the same questionnaire.The results show that the patient group has a statistically significant higher score of fatigue compared to the reference group (p = 0.004). However, the results must be interpreted with caution considering the relatively small sample size. In future research it is also important to investigate the relationship between fatigue and daily activities, depression, return to work, and quality of life.
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29.
  • Enblom, Sara, et al. (författare)
  • The Relationship between Health-Related Quality of Life, Subjective Scar Estimation, and Activity Performance in Adult Burn Patients 6 and 12 Months after Injury
  • 2022
  • Ingår i: European Burn Journal. - : MDPI. - 2673-1991. ; 3:4, s. 486-492
  • Tidskriftsartikel (refereegranskat)abstract
    • A burn injury affects a person’s health-related quality of life (HRQoL) in different ways and might influence their daily life for months and years afterward. The aim of this study was to examine how activity performance and subjective scar estimation relate to self-rated health and whether this changes in the first year post-burn. Fifty consecutive patients who were scheduled for follow-up at the Burn Center’s outpatient clinic in Uppsala were included. Assessments of HRQoL (EQ-5D), activity performance (DASH), and subjective scar evaluation (POSAS) were conducted at 6 and 12 months post-burn. The results show a statistically significant correlation between self-rated HRQoL and activity performance (p = 0.001) and between self-rated HRQoL and subjective scar estimation (p = 0.000) at 6 but not at 12 months post-burn. A possible explanation of the lack of correlation at one year post-burn might be the patient´s expectations of his or her recovery. In future research, it would be interesting to investigate the long-term correlations between quality of life and activity performance.
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33.
  • Fagerberg, Linn, et al. (författare)
  • Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
  • 2014
  • Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
  • Tidskriftsartikel (refereegranskat)abstract
    • Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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34.
  • Fransén, Jian, et al. (författare)
  • A proof-of-concept study on mortality prediction with machine learning algorithms using burn intensive care data
  • 2022
  • Ingår i: Scars, Burns & Healing. - : Sage Publications. - 2059-5131.
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionBurn injuries are a common traumatic injury. Large burns have high mortality requiring intensive care and accurate mortality predictions. To assess if machine learning (ML) could improve predictions, ML algorithms were tested and compared with the original and revised Baux score.MethodsAdmission data and mortality outcomes were collected from patients at Uppsala University Hospital Burn Centre from 2002 to 2019. Prognostic variables were selected, ML algorithms trained and predictions assessed by analysis of the area under the receiver operating characteristic curve (AUC). Comparison was made with Baux scores using DeLong test.ResultsA total of 17 prognostic variables were selected from 92 patients. AUCs in leave-one-out cross-validation for a decision tree model, an extreme boosting model, a random forest model, a support-vector machine (SVM) model and a generalised linear regression model (GLM) were 0.83 (95% confidence interval [CI] = 0.72–0.94), 0.92 (95% CI = 0.84–1), 0.92 (95% CI = 0.84–1), 0.92 (95% CI = 0.84–1) and 0.84 (95% CI = 0.74–0.94), respectively. AUCs for the Baux score and revised Baux score were 0.85 (95% CI = 0.75–0.95) and 0.84 (95% CI = 0.74–0.94). No significant differences were observed when comparing ML algorithms with Baux score and revised Baux score. Secondary variable selection was made to analyse model performance.ConclusionThis proof-of-concept study showed initial credibility in using ML algorithms to predict mortality in burn patients. The sample size was small and future studies are needed with larger sample sizes, further variable selections and prospective testing of the algorithms.
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35.
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36.
  • Fransén, Jian, et al. (författare)
  • Evaluating topical opioid gel on donor site pain : A small randomised double blind controlled trial
  • 2016
  • Ingår i: International Journal of Surgery Open. - : Elsevier BV. - 2405-8572. ; 4, s. 5-9
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAutologous donor skin harvested for transplantation is a common procedure in patients with burns, and patients often feel more pain at the donor site than is justified by the extent of trauma. Topical morphine gels have been thought to have an effect on peripheral opioid receptors by creating antinociceptive and anti-inflammatory effects, which could potentially reduce the systemic use of morphine-like substances and their adverse effects.MethodsWe therefore did a paired, randomised, double-blind placebo study to investigate the effect of morphine gel and placebo on dual donor sites that had been harvested in 13 patients. Pain was measured on a visual analogue scale (VAS) 15 times in a total of 5 days.ResultsThe mean (SD) VAS was 1.6 (2.3) for all sites, 1.5 (2.2) for morphine, and 2.0 (2.5) for placebo. The pain relieving effects of morphine gel were not significantly better than placebo.ConclusionThe assessment of pain at donor sites is subjective, and more systematic and objective studies are needed.
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37.
  • Fransén, Jian, 1986- (författare)
  • Large data and machine learning in analysis, diagnostics, and clinical decision making: applications in the treatment of burn injury
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Burn injury is a common trauma globally. Large burns require fluid resuscitation, infection control, and specialized intensive care. The size of the burn and infections caused by resistant microbes are correlated to mortality, and accurate mortality predictions are important. Errors are common when diagnosing burn depth, but early diagnosis is necessary to make correct surgical decisions. Machine learning (ML) is a set of mathematical algorithms with self-learning capabilities, which might make them suitable for medical applications.This thesis explores systematic large data analysis and ML algorithms for clinical applications in burn treatment by examining antibiotic resistance, improving mortality predictions, and automating diagnosis of burn depth.Paper I aims to find relevant trends and correlations on clinical outcomes such as mortality, microbial distribution, and antibiotic resistance from pooled data from a burn center. Data from 1570 patients and 15,006 microbiology cultures were systematically analyzed. Our results show a sustained low risk of harmful microbes, resistance, and a suggested low mortality rate.Paper II used clinical biomarkers from burn patients to train ML algorithms to predict mortality and compare it with Baux scores. When applying five types of ML algorithms, it showed no significant difference in mortality prediction compared with Baux scores.Paper III examines convolutional neural network (CNN) algorithms for two purposes. One to segment a burn wound and the other to classify whole wound images for surgery or conservative treatment. A total of 1105 diverse images were collected from patients at admission to burn centers in Sweden and South Africa. The algorithm was adequate for segmenting burn wounds and could be improved when categorizing images for surgery or conservative treatment.Paper IV further assesses CNN to automatically segment and diagnose a diverse set of early burn images for deep or superficial burn injury. A total of 1004 images were included. The algorithm proved adequate in segmenting superficial injuries but not deep injuries and performed similarly between darker and lighter skin patients.Future studies might incorporate infection variables in ML mortality predictions and larger sample sizes. Regarding automated burn image diagnosis, including multiple non-image variables might improve usability.
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38.
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39.
  • Fransen, Jian, et al. (författare)
  • Surveillance of antibiotic susceptibility in a Swedish Burn Center 1994-2012
  • 2016
  • Ingår i: Burns. - : Elsevier BV. - 0305-4179 .- 1879-1409. ; 42:6, s. 1295-1303
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with burn trauma are at risk for infections caused by antibiotic resistant bacteria (ABR) with subsequent increase in morbidity and mortality. As part of the Swedish strategic program against antibiotic resistance in intensive care (ICU-Strama), we have surveyed the distribution of species and ABR in isolates from patients admitted to a Swedish burn center at Linkoping University Hospital from 1994 through 2012. In an international comparison Strama has been successful in reducing the antibiotic consumption among animals and humans in primary care. The aim of this study was to investigate the antibiotic consumption pressure and resistance rates in a Swedish burn unit. Methods: Microbiology data, total body surface area (TBSA), patient days, and mortality were collected from a hospital database for all patients admitted to the Burn Center at the University Hospital of Linkoping from April 1994 through December 2012. Results: A total of 1570 patients were admitted with a mean annual admission rate of 83 patients (range: 57-152). 15,006 microbiology cultures (approximately 10 per patient) were collected during the study period and of these 4531 were positive (approximately 3 per patient). The annual mean total body surface area (TBSA) was 13.4% (range 9.5-18.5) with an annual mortality rate of 5.4% (range 1-8%). The MRSA incidence was 1.7% (15/866) which corresponds to an MRSA incidence of 0.34/1000 admission days (TAD). Corresponding figures were for Escherichia coli resistant to 3rd generation cephalosporins (ESBL phenotype) 8% (13/170) and 0.3/TAD, Klebsiella spp. ESBL phenotype 5% (6/134) and 0.14/TAD, carbapenem resistant Pseudomonas aeruginosa 26% (56/209) and 1.28/TAD, and carbapenem resistant Acinetobacter spp. 3% (2/64) and 0.04/TAD. Conclusions: Our results show a sustained low risk for MRSA and high, although not increasing, risk for carbapenem resistant P. aeruginosa.
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40.
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41.
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42.
  • Fredriksson, Camilla, et al. (författare)
  • Accumulation of Silver and Delayed Re-epithelialization in Normal Human Skin : An ex-vivo Study of Different Silver Dressings.
  • 2009
  • Ingår i: Wounds (King of Prussia, Pa.). - 1044-7946 .- 1943-2704. ; 21:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Silver is commonly used in wound dressings and topical formulations to assist in the management of wounds that are infected or at risk of becoming infected. They provide potent broad-spectrum antimicrobial activity, but should not cause sustained staining of the skin, dermal or systemic accumulation of silver, or discomfort to the patient. However, clinicians and healthcare personnel have been concerned about topical staining of the skin and complaints of additional pain from patients treated with certain silver dressings. Some delay in re-epithelialization has also been noticed and reported. The reasons for this are not clear, and the authors believed further study regarding the possible effects of silver accumulation and silver dressings' effect on re-epithelialization was required. The authors studied possible silver accumulation and re-epithelialization in normal human dermal skin. The results showed that most of the dressings or treatments discolored the wound surface and that there was a dermal accumulation of what were assumed to be silver particles. Varying grades of accumulation were found in deep dermal tissue, particularly around blood vessels, depending on the dressing used. The results also indicated that all of the tested products delayed re-epithelialization in this model. .
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43.
  • Fredriksson, Camilla, 1969- (författare)
  • Keratinocytes in tissue engineering of human skin: invitro and in vivo studies
  • 2008
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Full thickness wounds, such as deep burns, need restoration of both the dermal and epidermal layers of the skin. In normal wound healing, re-epithelialization occurs by migration and proliferation of keratinocytes from the wound edges and by differentiation of stem cells from remaining hair follicles. Restoration of dermis occurs by influx of growth factors secreted by macrophages, platelets, and fibroblasts; by fibroblast proliferation and subsequent synthesis and remodeling of collagenous dermal matrix. In the case of full-thickness acute burn injuries and chronic wounds (e.g. pressure ulcers, venous ulcers and diabetic foot ulcers), these processes are defective. With the principles of tissue engineering in mind (to correct, improve and maintain tissues and their functions), researchers have developed promising materials and methods to make it possible to restore either the dermal (Integra® DRT, Alloderm®) or the epidermal layer (split thickness skin grafts (STSG), cultured epithelial autografts (CEA), autologous keratinocytes in single cell suspension). It is now well established that superior results are obtained if both dermal and epidermal components are combined, for example in a bilayered skin equivalent. Apligraf® is recommended for use on venous ulcers and is the only bilayered living skin equivalent currently approved by the FDA. Studies on different factors affecting the wound healing capacity as well as techniques in use provide valuable information for further development.In this licentiate thesis, we evaluated different transplantation techniques for delivering cultured human keratinocytes in single cell suspension, a measure becoming more frequently used in addition to STSG and CEA for restoring the epidermal layer of the skin. We found that the pressure device, commonly used to spray cell suspension onto the wound with pressures as high as 200 kPa, killed around 0% of the cells. In comparison, an ordinary syringe with the attachment of a spray nozzle showed almost 90% viable cells post transplantation and provided an equally good distribution of the cell suspension.We also studied different silver containing dressings regarding silver accumulation in human skin. In addition, we graded the re-epithelialization to evaluate whether the dressings caused any delay in the wound healing process. We found that the silver dressings tested, with few exceptions, caused dermal accumulation of silver, primarily aggregated around blood vessels. We could also show that most of the dressings had negative effect on the re-epithelialization.For the restoration of the dermal layer of the skin, Integra® DRT functions as a scaffold for guided tissue regeneration of the dermis. We had the possibility to study a case of necrotizing fasciitis were the treatment consisted of the use of Integra® DTR together with sub-atmospheric pressure (after initial surgical debridement) and later transplantation of split thickness skin grafts. This measure proved to be safe as well as giving satisfactory pliable and aesthetically acceptable result.
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44.
  • Fredriksson, Camilla, et al. (författare)
  • Tissue Response to Subcutaneously Implanted Recombinant Spider Silk : An in Vivo Study
  • 2009
  • Ingår i: Materials. - Basel, Switzerland : MDPI AG. - 1996-1944. ; 2:4, s. 1908-1922
  • Tidskriftsartikel (refereegranskat)abstract
    • Spider silk is an interesting biomaterial for medical applications. Recently, a method for production of recombinant spider silk protein (4RepCT) that forms macroscopic fibres in physiological solution was developed. Herein, 4RepCT and MersilkTM (control) fibres were implanted subcutaneously in rats for seven days, without any negative systemic or local reactions. The tissue response, characterised by infiltration of macrophages and multinucleated cells, was similar with both fibres, while only the 4RepCT-fibres supported ingrowth of fibroblasts and newly formed capillaries. This in vivo study indicates that 4RepCT-fibres are well tolerated and could be used for medical applications, e.g., tissue engineering.
  •  
45.
  •  
46.
  • Fredriksson, Camilla, et al. (författare)
  • Transplantation of cultured human keratinocytes in single cell suspension: a comparative in vitro study of different application techniques
  • 2008
  • Ingår i: Burns. - : Institutionen för klinisk och experimentell medicin. - 0305-4179 .- 1879-1409. ; 34:2, s. 212-219
  • Tidskriftsartikel (refereegranskat)abstract
    • Transplantation of autologous cultured keratinocytes in single cell suspension is useful in the treatment of burns. The reduced time needed for culture, and the fact that keratinocytes in suspension can be transported from the laboratory to the patient in small vials, thus reducing the costs involved and be stored (frozen) in the clinic for transplantation when the wound surfaces are ready, makes it appealing. We found few published data in the literature about actual cell survival after transplantation of keratinocytes in single cell suspension and so did a comparative in vitro study, considering commonly used application techniques. Human primary keratinocytes were transplanted in vitro in a standard manner using different techniques. Keratinocytes were counted before and after transplantation, were subsequently allowed to proliferate, and counted again on days 4, 8, and 14 by vital staining. Cell survival varied, ranging from 47% to >90%, depending on the technique. However, the proliferation assays showed that the differences in numbers diminished after 8 days of culture. Our findings indicate that a great number of cells die during transplantation but that this effect is diminished if cells are allowed to proliferate in an optimal milieu. A burned patient’s wounds cannot be regarded as the optimal milieu, and using less harsh methods of transplantation may increase the take rate and wound closing properties of autologous keratinocytes transplanted in a single cell suspension.
  •  
47.
  • Frestadius, Andrea, et al. (författare)
  • Intranasal dexmedetomidine and rectal ketamine for young children undergoing burn wound procedures
  • 2022
  • Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 48:6, s. 1445-1451
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Safe and effective methods for sedation and analgesia in pediatric burn patients are strongly warranted. This retrospective study of electronic health care records aims to evaluate the safety and efficacy of intranasal dexmedetomidine combined with rectal ketamine as procedural sedation for young children undergoing dressing changes and debridement of burn wounds.Methods: Documentation was analyzed from 90 procedures in 58 pediatric patients aged <5 years. Safety and efficacy of the method were assessed based on documentation for complications, adverse effects, pain level, level of sedation and preoperative and recovery time.Results: All 90 sedations were completed without significant adverse events with acute airway management or medical intervention. The combination of dexmedetomidine-ketamine produced acceptable analgesia during the procedure and effectively relieved postoperative pain. However, the approach was insufficient for 7/58 patients (7.8%); these patients were converted from the dexmedetomidine-ketamine combination to intravenous anesthesia. In 23% of the cases an extra dose of either ketamine of dexmedetomidine was administered. Moreover, there were two cases of delayed awakening with recovery time >120 min.Conclusion: The drug combination intranasal dexmedetomidine and rectal ketamine is a safe and reliable approach for procedural sedation and analgesia in pediatric patients undergoing burn wound procedures, producing a clinically stable sedative condition requiring only basic monitoring.
  •  
48.
  • Frew, Quentin, et al. (författare)
  • Betulin wound gel accelerated healing of superficial partial thickness burns : Results of a randomized, intra-individually controlled, phase III trial with 12-months follow-up
  • 2019
  • Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 45:4, s. 876-890
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Acceleration of wound healing promises advantages for patients and caregivers in reducing the burden of disease, avoiding complications such as wound infections, and improving the long-term outcome. However, medicines that can accelerate wound healing are lacking. The objective of this open, blindly evaluated, randomized, multicenter phase III study was to compare intra-individually the efficacy and tolerability of Oleogel-S10 with fatty gauze dressing versus Octenilin (R) wound gel with fatty gauze dressing in accelerating the healing of superficial partial thickness burn wounds. Methods: Acute superficial partial thickness burn wounds in adults caused by fire, heat burn or scalding were divided into 2 halves and randomly assigned to treatment with Oleogel-S10 or Octenilin (R) wound gel. Photos for observer-blinded analysis of wound healing were taken at each wound dressing change. Percentages of reepithelialization were assessed at defined intervals. Efficacy and tolerability were evaluated based on a 5-point Likert scale. Results: Of 61 patients that were enrolled, 57 received the allocated intervention and 48 completed treatment. The percentage of patients with earlier wound healing was significantly higher for Oleogel-S10 (85.7%, n=30) compared to Octenilin (R) wound gel (14.3%, n= 5, p <0.0001). The mean intra-individual difference in time to wound closure was -1.0 day in favour of Oleogel-S10 (-1.4, -0.6; 95% CI, p <0.0001). Most investigators (87.0%) and patients (84.8%) evaluated the efficacy of Oleogel-S10 to be 'better' or 'much better' than that of Octenilin (R) wound gel. Long-term outcome 3 months and 12 months post injury was improved in some patients. Conclusions: Oleogel-S10 (Episalvan) significantly accelerated the healing of superficial partial thickness burn wounds. It was safe and well tolerated. (C) 2018 Elsevier Ltd and ISBI. All rights reserved.
  •  
49.
  • Garvin, Stina, et al. (författare)
  • Estradiol increases VEGF in human breast studied by whole-tissue culture.
  • 2006
  • Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 325:2, s. 245-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Sex steroid exposure constitutes a risk factor for breast cancer, but little is known about the effects of sex steroids on the normal breast, largely because of the lack of convenient models. We have developed a method of culturing normal breast tissue ex vivo. We have applied this method to investigate the effects of estradiol and progesterone on the key angiogenic mediator, vascular endothelial growth factor (VEGF), in the breast. Whole breast tissue was obtained from routine reduction mammoplasty. Tissue biopsies were cultured in vitro for 1-3 weeks, and the expression of luminal cytokeratin 18 was determined by immunohistochemistry. As an application, tissue biopsies were treated in vitro for 1 week with or without estradiol or estradiol and progesterone. Estrogen receptor, progesterone receptor, and Ki-67 were analyzed, and VEGF levels were examined by quantitative immunoassay and immunohistochemistry. Whole breast tissue was cultured ex vivo for 1 week with preserved morphology. Increased detachment of the luminal epithelium was observed after 2 weeks. Estradiol increased extracellular levels of VEGF in normal breast tissue biopsy medium. The addition of progesterone had neither stimulatory nor inhibitory effects on secreted VEGF. The method of whole breast tissue culturing thus provide a means by which to explore the biology of normal breast tissue. Our results suggest that estradiol exerts pro-angiogenic effects in normal breast by increasing levels of biologically active VEGF.
  •  
50.
  • Garvin, Stina, et al. (författare)
  • Estradiol increases VEGF in normal human breast studied by whole-tissue culture
  • 2006
  • Ingår i: Cell Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 325:2, s. 245-251
  • Tidskriftsartikel (refereegranskat)abstract
    • Sex steroid exposure constitutes a risk factor for breast cancer, but little is known about the effects of sex steroids on the normal breast, largely because of the lack of convenient models. We have developed a method of culturing normal breast tissue ex vivo. We have applied this method to investigate the effects of estradiol and progesterone on the key angiogenic mediator, vascular endothelial growth factor (VEGF), in the breast. Whole breast tissue was obtained from routine reduction mammoplasty. Tissue biopsies were cultured in vitro for 1–3 weeks, and the expression of luminal cytokeratin 18 was determined by immunohistochemistry. As an application, tissue biopsies were treated in vitro for 1 week with or without estradiol or estradiol and progesterone. Estrogen receptor, progesterone receptor, and Ki–67 were analyzed, and VEGF levels were examined by quantitative immunoassay and immunohistochemistry. Whole breast tissue was cultured ex vivo for 1 week with preserved morphology. Increased detachment of the luminal epithelium was observed after 2 weeks. Estradiol increased extracellular levels of VEGF in normal breast tissue biopsy medium. The addition of progesterone had neither stimulatory nor inhibitory effects on secreted VEGF. The method of whole breast tissue culturing thus provide a means by which to explore the biology of normal breast tissue. Our results suggest that estradiol exerts pro-angiogenic effects in normal breast by increasing levels of biologically active VEGF.
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