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  • 901.
    Westman, Anton
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Kirurgi.
    Björnstig, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Kirurgi.
    Injuries in Swedish skydiving2007In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 41, no 6, p. 356-364Article in journal (Refereed)
  • 902.
    Westman, Anton
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Rosén, M
    Berggren, P
    Björnstig, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Parachuting from fixed objects: descriptive study of 106 fatal events in BASE jumping 1981-20062008In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 42, no 6, p. 431-436Article in journal (Refereed)
    Abstract [en]

    Objective: To analyse the characteristics of fatal incidents in fixed object sport parachuting (building, antenna, span, earth (BASE) jumping) and create a basis for prevention.

    Design: Descriptive epidemiological study.

    Participants: Data on reported fatal injury events (n = 106) worldwide in 1981–2006 retrieved from the BASE fatality list.

    Assessment of risk factors: Human, equipment and environmental factors.

    Main outcome measurements: Identification of typical fatal incident and injury mechanisms for each of the four fixed object types of BASE jumping (building, antenna, span, earth).

    Results: Human factors included parachutist free fall instability (loss of body control before parachute deployment), free fall acrobatics and deployment failure by the parachutist. Equipment factors included pilot chute malfunction and parachute malfunction. In cliff jumping (BASE object type E), parachute opening towards the object jumped was the most frequent equipment factor. Environmental factors included poor visibility, strong or turbulent winds, cold and water. The overall annual fatality risk for all object types during the year 2002 was estimated at about one fatality per 60 participants.

    Conclusions: Participants in BASE jumping should target risk factors with training and technical interventions. The mechanisms described in this study should be used by rescue units to improve the management of incidents.

  • 903.
    Westman, Anton
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Sjöling, Mats
    Lindberg, Ann
    Björnstig, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    The SKYNET data: demography and injury reporting in Swedish skydiving.2010In: Accident Analysis and Prevention, ISSN 0001-4575, E-ISSN 1879-2057, Vol. 42, no 2, p. 778-783Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Swedish Parachute Association (SFF) national registry of skydiving injuries is one of the few trauma databases available for research on sport parachuting. The usefulness of this compulsory reporting system may benefit from a description of its base population and an evaluation of its sensitivity and specificity. METHODS: Cross-sectional analysis based on data collected through a web-based questionnaire (SKYNET), from all persons renewing a Swedish skydiving license 2008 (n=1049). Sensitivity was measured as the proportion of injury events fulfilling the reporting criterion (injury event requiring care of a physician) that were actually reported, by comparing the injury events reported to the SFF during the skydiving seasons 2006 and 2007 with the injury events retrospectively reported to the web-based questionnaire for the same time period. Specificity was measured as the proportion of false positives in relation to the defined reporting criterion for the same time period. Self-stated bone fractures, shoulder dislocations and cruciate ligament injuries were labeled as non-minor injuries. Factors affecting the likelihood of reporting were evaluated using logistic regression. RESULTS: The response rate was 100%. The overall sensitivity of the reporting system 2006/2007 was 0.37 (95% confidence interval (CI) 0.24-0.51). With self-stated non-minor injuries as the target for reporting, the sensitivity was 0.67 (95% CI 0.43-0.85). No significant effect on reporting was found for gender, age, license level, years in the sport, total number of jumps or club affiliation. The specificity was 0.91 (95% CI 0.83-0.95). Descriptive statistics of the Swedish skydiving population show several gender differences. CONCLUSIONS: The low sensitivity will yield false low incidence calculations, but as there is no evidence for differential underreporting, risk comparisons related to the candidate predictor variables appear reasonably valid. The false positive reporting warrants assortment of incoming data and a clarification of the reporting criteria. Attitudes to reporting may be of value to study, to understand the drivers and constraints for achieving a more complete notification of skydiving injuries.

  • 904.
    Westman, Anton
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sjöling, Mats
    Research and Development Centre, County Council of Västernorrland.
    Lindberg, Ann
    Department of Disease Control, National Veterinary Institute .
    Björnstig, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Validity of injury reporting among active Swedish skydivers2009Manuscript (preprint) (Other academic)
    Abstract [en]

    Objective: Evaluation of a national compulsory reporting system for skydiving injuries.

    Design: Self-report survey.

    Setting: The Swedish Parachute Association (SFF).

    Subjects: All persons renewing a Swedish skydiving license 2008 (n=1049).

    Main outcome measures: Sensitivity was measured as the proportion of injury events fulfilling the reporting criterion that were actually reported; Specificity was measured as the proportion of false positives in relation to the defined gold standard. Self-stated bone fractures, shoulder dislocations and cruciate ligament injuries were labeled as non-minor injuries.

    Results: The response rate was 100%. The overall sensitivity of the reporting system 2006/2007 was 0.37 (95% confidence interval (CI) 0.24-0.51). With selfstated non-minor injuries as the target for reporting, the sensitivity was 0.67 (95% CI 0.43-0.85). No significant effect on reporting was found for gender, age, license level, years in the sport, total number of jumps or club affiliation. The specificity was 0.91 (95% CI 0.83-0.95).

    Conclusions: The low sensitivity will yield false low incidence calculations, but risk comparisons related to the candidate predictor variables appear reasonably valid. The false positive reporting warrants assortment of incoming data and a clarification of the reporting criterions. We propose the addition of “hospitalization Yes/No” in future reporting and endorse coordinating skydiving data collection in the Nordic countries. Further studies on attitudes to reporting are necessary to understand the drivers and constraints for achieving a more complete notification of skydiving injuries. 

  • 905.
    Westrin, Charlotte
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Perioperative evaluation of liver metabolism by surface microdialysis – An explorative pilot study2019Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 906.
    Wikberg, Maria L.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Edin, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundberg, Ida V.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dahlin, Anna M.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis.2013In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 34, no 2, p. 1013-1020Article in journal (Refereed)
    Abstract [en]

    -An active stroma is important for cancer cell invasion and metastasis. We investigated the expression of fibroblast activation protein (FAP) in relation to patient prognosis in colorectal cancer. Colorectal cancer specimens from 449 patients were immunohistochemically stained with a FAP antibody and evaluated in the tumor center and tumor front using a semiquantitative four-level scale. FAP was expressed by fibroblasts in 85-90 % of the tumors examined. High versus no/low expression in the tumor center was associated with poor prognosis (multivariate hazard ratio, HR = 1.72; 95 % CI 1.07-2.77, p = 0.025). FAP expression in the tumor front, though more frequent than in the tumor center, was not associated with prognosis. FAP expression in the tumor center was more common in specimens with positive microsatellite instability (MSI) screening status and in patients with high CpG island methylator phenotype (CIMP) status. However, inclusion of MSI screening status and CIMP status in the multivariate analysis strengthened the risk estimates for high FAP expression in the tumor center (HR = 1.89; 95 % CI 1.13-3.14; p = 0.014), emphasizing the role of FAP as an independent prognostic factor. Stromal FAP expression is common in colorectal cancer, and we conclude that high FAP expression in the tumor center, but not the tumor front, is an independent negative prognostic factor.

  • 907.
    Wikberg, Maria L.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ling, Agnes
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Li, Xingru
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Edin, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Neutrophil infiltration is a favorable prognostic factor in early stages of colon cancer2017In: Human Pathology, ISSN 0046-8177, E-ISSN 1532-8392, Vol. 68, p. 193-202Article in journal (Refereed)
    Abstract [en]

    The tumor immune response has been proven critical to prognosis in colorectal cancer (CRC), but studies on the prognostic role of neutrophil infiltration have shown contradictory results. The aim of this study was to elucidate the prognostic role of infiltrating neutrophils at different intratumoral subsites and in different molecular subgroups of CRC. The relations between neutrophil infiltration and infiltration of other immune cells (T-cell and macrophage subsets) were also addressed. Expression of the neutrophil marker CD66b was assessed by immunohistochemistry in 448 archival human tumor tissue samples from patients surgically resected for CRC. The infiltration of CD66b-positive cells was semi-quantitatively evaluated along the tumor invasive front, in the tumor center, and within the tumor epithelium (intraepithelial expression). We found that poor infiltration of CD66b-positive cells in the tumor front indicated a worse patient prognosis. The prognostic significance of CD66b infiltration was found to be mainly independent of tumor molecular characteristics and maintained significance in multivariable analysis of stage I-II colon cancers. We further analyzed the prognostic impact of CD66b-positive cells in relation to other immune markers (NOS2, CD163, Tbet, FOXP3, and CD8) and found that neutrophil infiltration, even though strongly correlated to infiltration of other immune cell subsets, had additional prognostic value. In conclusion, we find that low infiltration of neutrophils in the tumor front is an independent prognostic factor for a poorer patient prognosis in early stages of colon cancers. Further studies are needed to elucidate the biological role of neutrophils in colorectal carcinogenesis.

  • 908.
    Wiklander, Linn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Surgical long-term results and quality of life after treatment with open abdomen2019Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 909.
    Wiklund, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Marcus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Öström, Mats
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Forensic Medicine.
    Messner, Torbjörn
    Influence of energy drinks and alcohol on post-exercise heart rate recovery and heart rate variability2009In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 29, no 1, p. 74-80Article in journal (Refereed)
    Abstract [sv]

    Background: Media have anecdotally reported that drinking energy drinks in combination with alcohol and exercise could cause sudden cardiac death. This study investigated changes in the electrocardiogram (ECG) and heart rate variability after intake of an energy drink, taken in combination with alcohol and exercise.

    Methods: Ten healthy volunteers (five men and five women aged 19–30) performed maximal bicycle ergometer exercise for 30 min after: (i) intake of 0·75 l of an energy drink mixed with alcohol; (ii) intake of energy drink; and, (iii) no intake of any drink. ECG was continuously recorded for analysis of heart rate variability and heart rate recovery.

    Results: No subject developed any clinically significant arrhythmias. Post-exercise recovery in heart rate and heart rate variability was slower after the subjects consumed energy drink and alcohol before exercise, than after exercise alone.

    Conclusion: The healthy subjects developed blunted cardiac autonomic modulation after exercising when they had consumed energy drinks mixed with alcohol. Although they did not develop any significant arrhythmia, individuals predisposed to arrhythmia by congenital or other rhythm disorders could have an increased risk for malignant cardiac arrhythmia in similar situations.

  • 910.
    Wikstrand, Victoria
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Linder, Nadja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Evaluation of the Doppler technique for fat emboli detection in an experimental flow model2008In: The Journal of extra-corporeal technology, ISSN 0022-1058, Vol. 40, no 3, p. 175-183Article in journal (Refereed)
    Abstract [en]

    Pericardial suction blood (PSB) is known to be contaminated with fat droplets, which may cause embolic brain damage during cardiopulmonary bypass (CPB). This study aimed to investigate the possibility to detect fat emboli by a Doppler technique. An in vitro flow model was designed, with a main pump, a filter, a reservoir, and an injector. A Hatteland Doppler probe was attached to the circulation loop to monitor particle counts and their size distribution. Suspended soya oil or heat-extracted human wound fat was analyzed in the model. The concentrations of these fat emboli were calibrated to simulate clinical conditions with either a continuous return of PSB to the systemic circulation or when PSB was collected for rapid infusion at CPB weaning. For validation purpose, air and solid emboli were also analyzed. Digital image analysis was performed to characterize the nature of the tested emboli. With soya suspension, there was an apparent dose response between Doppler counts and the nominal fat concentration. This pattern was seen for computed Doppler output (p = .037) but not for Doppler raw counts (p = .434). No correlation was seen when human fat suspensions were tested. Conversely, the image analysis showed an obvious relationship between microscopy particle count and the nominal fat concentration (p < .001). However, the scatter plot between image analysis counting and Doppler recordings showed a random distribution (p = .873). It was evident that the Doppler heavily underestimated the true number of injected fat emboli. When the image analysis data were subdivided into diameter intervals, it was discovered that the few large-size droplets accounted for a majority of total fat volume compared with the numerous small-size particles (< 10 microm). Our findings strongly suggest that the echogenecity of fat droplets is insufficient for detection by means of the tested Doppler method.

  • 911.
    Winsnes, Annika
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Surgical intervention in primary umbilical hernia A register study of complications and recurrences.2014Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 912.
    Winsnes, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Gunnarsson, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Falk, Peter
    Stark, Birgit
    Moskaug, Jan Ø.
    Strigård, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Evaluating full-thickness skin grafts in intraperitoneal onlay mesh position versus onlay position in mice2018In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 230, p. 155-163Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Importance: Hernia surgery requires reinforcement material with few side effects when used in the intraperitoneal position. Autologous skin grafting may meet this requirement, but animal experiments are obligatory before being applied in humans.

    OBJECTIVE: To compare survival and effects of isogeneic full-thickness skin grafts in the intraperitoneal onlay mesh (IPOM) position in mice, with a control group using the onlay position. Primary end point was graft survival and secondary end point adhesion formation and inflammation through NF-κB activity.

    METHODS: Design: Intervention study with 8-week follow-up in accordance with ARRIVE criteria, performed between 2015 and 2016.

    SETTING: Animal laboratory.

    PARTICIPANTS: Transgenic C57BL/6 mice with isogeneic background were used. Recipients were female wild-type phenotype mice >3 mo (n = 24). Donors were male or female mice >7 mo, with phenotype-positive for the luciferase gene (n = 20) or positive for NF-κB-luciferase gene (n = 4).

    INTERVENTION: Full-thickness skin was grafted in the IPOM position and compared with grafts in the onlay position as controls. Survival was evaluated by regular longitudinal postoperative luminescence imaging over 8 wk. Adherence formation was evaluated macroscopically after sacrifice. Inflammation of full-thickness skin grafts in IPOM position of NF-κB mice was evaluated in four additional mice. Main outcome and measure: Survival of grafts, evaluated by luminescence.

    RESULTS: Ten animals received grafts in the IPOM position, and 10 in the onlay position as controls. Graft survival after 8 wk was 100% (20/20). Average luminescence at the end of the 8-week period was 999,597 flux (min 162,800, max 2,521,530) in the IPOM group (n = 10) and 769,708 flux (min 76,590, max 2,164,080) in the onlay control group (n = 10). No adhesions requiring sharp dissection (Jenkins' scale >2) were seen. Four animals with grafts in the IPOM position showed peak inflammation (NF-κB activity) 5 d after surgery subsiding toward the end of follow-up.

    CONCLUSIONS: Full-thickness skin survives as well in the IPOM position as in the onlay control position, and few adherences develop. Further studies are required to fully characterize the tissue remodeling and repair processes associated with IPOM skin grafting. The result is relevant in the search for alternative reinforcement materials to be used in complex hernia surgery in humans.

  • 913.
    Winsnes, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Haapamäki, Markku
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Gunnarsson, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Strigård, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Surgical outcome of mesh and suture repair in primary umbilical hernia: postoperative complications and recurrence2016In: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 20, no 4, p. 509-516Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare recurrence and surgical complications following two dominating techniques: the use of suture and mesh in umbilical hernia repair.

    METHODS: 379 consecutive umbilical hernia repair procedures performed between 1 January 2005 and 14 March 2014 in a university setting were included. Gathering was made using International Classification of Diseases codes for both procedure and diagnosis. Each patient record was scrutinized with respect to 45 variables, and the results entered in a database.

    RESULTS: Exclusion <18 years-of-age (32), non-primary umbilical hernia (25), wrong diagnosis (7), concomitant major abdominal surgery (5), double registration (3) and pregnancy (1) left 306 patients eligible for analysis. Gender distribution was 97 women and 209 men. There was no difference between mesh and suture with regard to the primary outcome variable, cumulative recurrence rate, 8.4 %. Recurrence was both self-reported and found on clinical revisit and defined as recurrence when verified by a clinician and/or radiologist. Results presented as odds ratio (OR) with 95 % confidence interval (CI) show a significantly higher risk for recurrence in patients with a coexisting hernia OR 2.84, 95 % CI 1.24-6.48. Secondary outcome, postoperative surgical complication (n = 51 occurrences), included an array of postoperative surgical events commencing within 30 days after surgery. Complication rate was significantly higher in patients receiving mesh repair OR 6.63, 95 % CI 2.29-20.38.

    CONCLUSIONS: Suture repair decreases the risk for surgical complications, especially infection without an increase in recurrence rate. The risk for recurrence is increased in patients with a history of another hernia.

  • 914.
    Winsö, Ola
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Kral, Josef
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Wang, Wanzhong
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Kralova, Ivana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Blind, Per-Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Thoracic epidural anaesthesia reduces insulin resistance and inflammatory response in experimental acute pancreatitis2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 207-215Article in journal (Refereed)
    Abstract [en]

    AIMS: The activity of the sympathetic nervous system (SNS) is crucial at an early stage in the development of an inflammatory reaction. A study of metabolic events globally and locally in the early phase of acute pancreatitis (AP), implying hampered SNS activity, is lacking. We hypothesized that thoracic epidural anaesthesia (TEA) modulates the inflammatory response and alleviates the severity of AP in pigs.

    MATERIAL AND METHODS: The taurocholate (TC) group (n = 8) had only TC AP. The TC + TEA group (n = 8) had AP and TEA. A control group (n = 8) underwent all the preparations, without having AP or TEA. Metabolic changes in the pancreas were evaluated by microdialysis and by histopathological examination.

    RESULTS: The relative increase in serum lipase concentrations was more pronounced in the TC group than in TC + TEA and control groups. A decrease in relative tissue oxygen tension (PtiO2) levels occurred one hour later in the TC + TEA group than in the TC group. The maintenance of normoglycaemia in the TC group required a higher glucose infusion rate than in the TC + TEA group. The relative decrease in serum insulin concentrations was most pronounced in the TC + TEA group.

    CONCLUSION: TEA attenuates the development of AP, as indicated by changes observed in haemodynamic parameters and by the easier maintenance of glucose homeostasis. Further, TEA was associated with attenuated insulin resistance and fewer local pathophysiological events.

  • 915.
    Wählby, Lennart
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Achilles tendon injury: aspects on muscle structure and strength1978Doctoral thesis, comprehensive summary (Other academic)
  • 916. Ylönen, Riikka
    et al.
    Kyrönlahti, Tuomo
    Sund, Malin
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Ilves, Mika
    Lehenkari, Petri
    Tuukkanen, Juha
    Pihlajaniemi, Taina
    Type XIII collagen strongly affects bone formation in transgenic mice.2005In: J Bone Miner Res, ISSN 0884-0431, Vol. 20, no 8, p. 1381-93Article in journal (Refereed)
  • 917. Zamora-Ros, Raul
    et al.
    Fedirko, Veronika
    Trichopoulou, Antonia
    González, Carlos A
    Bamia, Christina
    Trepo, Elisabeth
    Nöthlings, Ute
    Duarte-Salles, Talita
    Serafini, Mauro
    Bredsdorff, Lea
    Overvad, Kim
    Tjønneland, Anne
    Halkjaer, Jytte
    Fagherazzi, Guy
    Perquier, Florence
    Boutron-Ruault, Marie-Christine
    Katzke, Verena
    Lukanova, Annekatrin
    Floegel, Anna
    Boeing, Heiner
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Saieva, Calogero
    Agnoli, Claudia
    Mattiello, Amalia
    Tumino, Rosario
    Sacerdote, Carlotta
    Bas Bueno-de-Mesquita, H
    Peeters, Petra H M
    Weiderpass, Elisabete
    Engeset, Dagrun
    Skeie, Guri
    Vicente Argüelles, Marcial
    Molina-Montes, Esther
    Dorronsoro, Miren
    José Tormo, María
    Ardanaz, Eva
    Ericson, Ulrika
    Sonestedt, Emily
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Landberg, Rikard
    Khaw, Kay-Tee
    Wareham, Nicholas J
    Crowe, Francesca L
    Riboli, Elio
    Jenab, Mazda
    Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 133, no 10, p. 2429-2443Article in journal (Refereed)
    Abstract [en]

    Limited epidemiological evidence suggests a protective role for plant foods rich in flavonoids and antioxidants in hepatocellular cancer (HCC) etiology. Our aim was to prospectively investigate the association between dietary intake of flavonoids, lignans and nonenzymatic antioxidant capacity (NEAC) and HCC risk. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 477,206 subjects (29.8% male) recruited from ten Western European countries, was analyzed. Flavonoid, lignan and NEAC intakes were calculated using a compilation of existing food composition databases linked to dietary information from validated dietary questionnaires. Dietary NEAC was based on ferric reducing antioxidant capacity (FRAP) and total radical-trapping antioxidant parameter (TRAP). Hepatitis B/C status was measured in a nested case-control subset. During a mean follow-up of 11-years, 191 incident HCC cases (66.5% men) were identified. Using Cox regression, multivariable adjusted models showed a borderline nonsignificant association of HCC with total flavonoid intake (highest versus lowest tertile, HR = 0.65, 95% CI: 0.40-1.04; ptrend  = 0.065), but not with lignans. Among flavonoid subclasses, flavanols were inversely associated with HCC risk (HR = 0.62, 95% CI: 0.39-0.99; ptrend  = 0.06). Dietary NEAC was inversely associated with HCC (FRAP: HR 0.50, 95% CI: 0.31-0.81; ptrend  = 0.001; TRAP: HR 0.49, 95% CI: 0.31-0.79; ptrend  = 0.002), but statistical significance was lost after exclusion of the first 2 years of follow-up. This study suggests that higher intake of dietary flavanols and antioxidants may be associated with a reduced HCC risk.

  • 918. Zamora-Ros, Raul
    et al.
    Ferrari, Pietro
    Gonzalez, Carlos A.
    Tjonneland, Anne
    Olsen, Anja
    Bredsdorff, Lea
    Overvad, Kim
    Touillaud, Marina
    Perquier, Florence
    Fagherazzi, Guy
    Lukanova, Annekatrin
    Tikk, Kaja
    Aleksandrova, Krasimira
    Boeing, Heiner
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Dilis, Vardis
    Masala, Giovanna
    Sieri, Sabina
    Mattiello, Amalia
    Tumino, Rosario
    Ricceri, Fulvio
    Bueno-de-Mesquita, H. Bas
    Peeters, Petra H. M.
    Weiderpass, Elisabete
    Skeie, Guri
    Engeset, Dagrun
    Menendez, Virginia
    Travier, Noemie
    Molina-Montes, Esther
    Amiano, Pilar
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Wallstrom, Peter
    Sonestedt, Emily
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Landberg, Rikard
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Travis, Ruth C.
    Scalbert, Augustin
    Ward, Heather A.
    Riboli, Elio
    Romieu, Isabelle
    Dietary flavonoid and lignan intake and breast cancer risk according to menopause and hormone receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study2013In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 139, no 1, p. 163-176Article in journal (Refereed)
    Abstract [en]

    Evidence on the association between dietary flavonoids and lignans and breast cancer (BC) risk is inconclusive, with the possible exception of isoflavones in Asian countries. Therefore, we investigated prospectively dietary total and subclasses of flavonoid and lignan intake and BC risk according to menopause and hormonal receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 334,850 women, mostly aged between 35 and 70 years from ten European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the US Department of Agriculture, the Phenol-Explorer and the UK Food Standards Agency databases. Cox regression models were used to analyse the association between dietary flavonoid/lignan intake and the risk of developing BC. During an average 11.5-year follow-up, 11,576 incident BC cases were identified. No association was observed between the intake of total flavonoids [hazard ratio comparing fifth to first quintile (HRQ5-Q1) 0.97, 95 % confidence interval (CI): 0.90-1.04; P trend = 0.591], isoflavones (HRQ5-Q1 1.00, 95 % CI: 0.91-1.10; P trend = 0.734), or total lignans (HRQ5-Q1 1.02, 95 % CI: 0.93-1.11; P trend = 0.469) and overall BC risk. The stratification of the results by menopausal status at recruitment or the differentiation of BC cases according to oestrogen and progesterone receptors did not affect the results. This study shows no associations between flavonoid and lignan intake and BC risk, overall or after taking into account menopausal status and BC hormone receptors.

  • 919. Zamora-Ros, Raul
    et al.
    Luján-Barroso, Leila
    Bueno-de-Mesquita, H Bas
    Dik, Vincent K
    Boeing, Heiner
    Steffen, Annika
    Tjønneland, Anne
    Olsen, Anja
    Bech, Bodil Hammer
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Fagherazzi, Guy
    Kuhn, Tilman
    Katzke, Verena
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Tumino, Rosario
    Panico, Salvatore
    Vineis, Paolo
    Grioni, Sara
    Palli, Domenico
    Weiderpass, Elisabete
    Skeie, Guri
    Huerta, José María
    Sánchez, María-José
    Argüelles, Marcial
    Amiano, Pilar
    Ardanaz, Eva
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindkvist, Björn
    Wallström, Peter
    Peeters, Petra H M
    Key, Timothy J
    Khaw, Kay-Thee
    Wareham, Nicholas J
    Freisling, Heinz
    Stepien, Magdalena
    Ferrari, Pietro
    Gunter, Marc J
    Murphy, Neil
    Riboli, Elio
    González, Carlos A
    Tea and coffee consumption and risk of esophageal cancer: the European Prospective Investigation into Cancer and Nutrition (EPIC) study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 6, p. 1470-1479Article in journal (Refereed)
    Abstract [en]

    Epidemiological data regarding tea and coffee consumption and risk of esophageal cancer (EC) is still inconclusive. We examined the association of tea and coffee consumption with EC risk among 442,143 men and women without cancer at baseline from 9 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC). Tea and coffee intakes were recorded using country-specific validated dietary questionnaires. Cox regression models were used to analyze the relationships between tea and coffee intake and EC risk. During a mean follow-up of 11.1 years, 339 participants developed EC, of which 142 were esophageal adenocarcinoma (EAC) and 174 were esophageal squamous cell carcinoma (ESCC). In the multivariable models, no significant associations between tea (mostly black tea), and coffee intake and risk of EC, EAC and ESCC were observed. In stratified analyses, among men coffee consumption was inversely related to ESCC (HR for comparison of extreme tertiles 0.42, 95% CI 0.20-0.88; P-trend=0.022), but not among women. In current smokers, a significant and inverse association was observed between ESCC risk and tea (HR 0.46, 95% CI 0.23-0.93; P-trend=0.053) and coffee consumption (HR 0.37, 95% CI 0.19-0.73; P-trend=0.011). However, no statistically significant findings were observed using the continuous variable (per 100mL/d). These data did not show a significant association between tea and coffee consumption and EC, EAC and ESCC, although a decreased risk of ESCC among men and current smokers is suggested, but need to be confirmed in further prospective studies including more cases.

  • 920. Zamora-Ros, Raul
    et al.
    Rinaldi, Sabina
    Biessy, Carine
    Tjonneland, Anne
    Halkjaer, Jytte
    Fournier, Agnes
    Boutron-Ruault, Marie-Christine
    Mesrine, Sylvie
    Tikk, Kaja
    Fortner, Renee T.
    Boeing, Heiner
    Foerster, Jana
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Papatesta, Eleni-Maria
    Masala, Giovanna
    Tagliabue, Giovanna
    Panico, Salvatore
    Tumino, Rosario
    Polidoro, Silvia
    Peeters, Petra H. M.
    Bueno-de-Mesquita, H. B(as)
    Weiderpass, Elisabete
    Lund, Eiliv
    Argueelles, Marcial
    Agudo, Antonio
    Molina-Montes, Esther
    Navarro, Carmen
    Barricarte, Aurelio
    Larranaga, Nerea
    Manjer, Jonas
    Almquist, Martin
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hennings, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Tsilidis, Konstantinos K.
    Schmidt, Julie A.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Romieu, Isabelle
    Byrnes, Graham
    Gunter, Marc J.
    Riboli, Elio
    Franceschi, Silvia
    Reproductive and menstrual factors and risk of differentiated thyroid carcinoma: The EPIC study2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 5, p. 1218-1227Article in journal (Refereed)
    Abstract [en]

    Differentiated thyroid carcinoma (TC) is threefold more common in women than in men and, therefore, a role of female hormones in the etiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mean age 51) followed for an average of 11 years, 508 differentiated TC cases were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No significant associations were observed between differentiated TC risk and number of pregnancies, breast feeding, menopausal status, and age at menarche and at menopause. Significant associations were found with history of infertility problems (HR 1.70; 95% CI 1.12-2.60), a recent pregnancy (HR for 5 vs. >5 years before recruitment 3.87; 95% CI 1.43-10.46), menopause type (HR for surgical vs. natural menopause: 2.16; 95% CI 1.41-3.31), oral contraceptive (OC) use at recruitment (HR: 0.48; 95% CI 0.25-0.92) and duration of OC use (HR for 9 vs. 1 year: 0.66; 95% CI: 0.50-0.89). An increased risk was also found with hormone replacement therapy use at recruitment (HR=1.30, 95% CI 1.02-1.67), but this was not significant after adjustment for type of menopause (HR=1.22, 95% CI 0.95-1.57). Overall, our findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the etiology of differentiated TC. The few observed associations may be real or accounted for by increased surveillance in women who had infertility problems, recent pregnancies or underwent surgical menopause.

  • 921. Zamora-Ros, Raul
    et al.
    Rinaldi, Sabina
    Tsilidis, Konstantinos K.
    Weiderpass, Elisabete
    Boutron-Ruault, Marie-Christine
    Rostgaard-Hansen, Agnetha Linn
    Tjonneland, Anne
    Clavel-Chapelon, Francoise
    Mesrine, Sylvie
    Katzke, Verena A.
    Kuehn, Tilman
    Foerster, Jana
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Klinaki, Eleni
    Masala, Giovanna
    Sieri, Sabina
    Ricceri, Fulvio
    Tumino, Rosario
    Mattiello, Amalia
    Peeters, Petra H. M.
    Bueno-de-Mesquita, H. B(as)
    Engeset, Dagrun
    Skeie, Guri
    Argueelles, Marcial
    Agudo, Antonio
    Sanchez, Maria-Jose
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Chamosa, Saioa
    Almquist, Martin
    Tosovic, Ada
    Hennings, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schmidt, Julie A.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Cross, Amanda J.
    Slimani, Nadia
    Byrnes, Graham
    Romieu, Isabelle
    Riboli, Elio
    Franceschi, Silvia
    Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 1, p. 65-73Article in journal (Refereed)
    Abstract [en]

    Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle-age participants (70.2% women) from ten European countries. Dietary data were collected using country-specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow-up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HRQ4vs.Q1, 1.29; 95% CI, 1.00-1.68) and PUFA intakes (HRQ4vs.Q1, 0.74; 95% CI, 0.57-0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI25 and with sugar intake in those with BMI<25. Moreover, inverse associations with starch and GI were observed in subjects with BMI<25. In conclusion, our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC. Positive associations with starch intake and GI in participants with BMI25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people. What's New? The role of lifestyle factors in the growing numbers of thyroid cancer remains unclear. Here, the authors uncover associations with high total energy intake and low consumption of polyunsaturated fatty acids in a large European cohort (EPIC). They further find positive associations with starch intake and glycemic index only in people with a body mass index equal or larger than 25, possibly implicating an altered insulin response in the etiology of this cancer.

  • 922.
    Zhao, Ying
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå Heart Centre.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Accentuated left ventricular lateral wall function compensates for septal dyssynchrony after valve replacement for aortic stenosis2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 164, no 3, p. 339-344Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The interventricular septal motion becomes reversed after aortic valve replacement (AVR) for aortic stenosis (AS) despite maintained stroke volume (SV). We hypothesis that left ventricular (LV) lateral wall compensates for such disturbances, in order to secure normal SV. METHODS: We studied 29 severe AS patients (age 63±11years, 18 males) with normal ejection fraction (EF) before, 6months and 12months after AVR and compared them with 29 age- and gender-matched controls, using speckle tracking echocardiography. RESULTS: In patients, the LVEF and SV remained unchanged throughout. Before AVR, the septal radial motion, septal and lateral strain were reduced (p<0.001). Peak septal and lateral displacements, times from QRS to peak displacement were all not different from controls. Six months after AVR, septal radial motion reversed (p<0.001), lateral strain increased (p<0.05), peak septal displacement reduced (p<0.01) while lateral displacement increased (p<0.05). Time to peak septal displacement delayed (p<0.01) in contrast to lateral displacement which became early (p<0.05), resulting in a significant septal-lateral time delay (p<0.01). The accentuation of LV lateral wall correlated with septal displacement time delay (r=0.60, p<0.001) and septal-lateral time delay (r=0.64, p<0.001). SV correlated with lateral displacement (r=0.39, p<0.05). The systolic strain was correlated with opposite wall displacement (p<0.05 for both). There was no correlation between these measurements before and 12month after AVR. CONCLUSIONS: Accentuated lateral wall displacement compensates for septal dyssynchrony in order to maintain normal LVEF and SV. The continuing recovery of these disturbances 12months after complete mass regression suggests an ongoing reverse remodeling.

  • 923.
    Zhao, Ying
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nilsson, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Trans-catheter aortic valve implantation: early recovery of left and preservation of right ventricular function2011In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 12, no 1, p. 35-39Article in journal (Refereed)
    Abstract [en]

    This study aimed to assess the early effect of trans-catheter aortic valve implantation (TAVI) on right (RV) and left ventricular (LV) function in severe aortic stenosis (AS) patients. Twenty AS patients (age 79±6 years) were examined before, one week and six weeks after TAVI using Doppler echocardiography. LV ejection fraction (EF), long-axis [mitral annular plane systolic excursion (MAPSE)] and RV long-axis [tricuspid annular plane systolic excursion (TAPSE)] function, septal radial motion were studied. Results were compared with 30 AS patients before and one week after aortic valve replacement (AVR) as well as 30 normals (reference group). Before TAVI, LVEF was reduced and E/A was higher than the reference and AVR groups (P<0.05 for all). MAPSE, TAPSE and septal motion were equally reduced in TAVI and AVR patients (P<0.05 for all). One week after the TAVI, EF increased in patients with values <50% before the procedure. In contrast, AVR resulted in reversed septal motion (P<0.001) and depressed TAPSE (P<0.001). The extent of reversed septal motion correlated with that of TAPSE in the patients group as a whole after procedures (r=0.78, P<0.001). Six weeks after TAVI, RV function remained unchanged, but LVEF increased and E/A decreased (P<0.05 for both). Thus, TAVI procedure results in significant early improvement of LV systolic and diastolic function particularly in patients with reduced EF and preserves RV systolic function.

  • 924. Zheng, Jiaojiao
    et al.
    Rutegård, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Santoni, Giola
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Xie, Shao-Hua
    Lagergren, Jesper
    Prediabetes and diabetes in relation to risk of gastric adenocarcinoma2019In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 120, no 12, p. 1147-1152Article in journal (Refereed)
    Abstract [en]

    Background: Whether prediabetes or diabetes increases the risk of gastric adenocarcinoma is not clear.

    Methods: This cohort study included 111,198 participants in the Northern Swedish Health and Disease Study. The participants were followed up from November 1985 to April 2017. The exposure to prediabetes or diabetes was assessed by oral glucose tolerance tests and self-reports. The incidence of the outcome gastric adenocarcinoma was identified from the Swedish Cancer Registry. Multivariable Cox regressions were used to analyse the associations between prediabetes or diabetes and the risk of gastric adenocarcinoma, providing hazard ratios (HR) with 95% confidence intervals (CI), with adjustment for sex, age, calendar year, body mass index, tobacco smoking and education level.

    Results: Compared with normoglycaemic participants, the risk of gastric adenocarcinoma was not increased among participants with prediabetes (HR 1.07, 95% CI 0.79–1.44), diabetes (HR 0.77, 95% CI 0.46–1.29) or any of these exposures (HR 0.96, 95% CI 0.73–1.27). No associations were identified between prediabetes or diabetes and the risk of gastric adenocarcinoma in stratified analyses or in analyses separating cardia and non-cardia gastric adenocarcinoma.

    Conclusions: This study does not support the hypothesis that prediabetes or diabetes increases the risk of gastric adenocarcinoma.

  • 925.
    Åberg, Torkel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Symposium for the future of cardiac surgery. Working group report. If retreat, how?2004In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 26, no Suppl 1, p. S72-S73Article in journal (Other (popular science, discussion, etc.))
  • 926.
    Åberg, Torkel
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Hentschel, J
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Nio års registrering vid hjärtcentrum visar att medicinska resultat förbättrats2004In: Läkartidningen, Vol. 102, p. 26-29Article in journal (Refereed)
  • 927.
    Åberg, Torkel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Hentschel, Jan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Improved total quality by monitoring of a cardiothoracic unit. Medical, administrative and economic data followed for 9 years.2004In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 3, no 1, p. 33-40Article in journal (Refereed)
    Abstract [en]

    To describe monitoring of a cardio-thoracic department from a total quality aspect point of view and to follow the development over 9 years. During the time period 1994-2002 a total of 10,828 cardio-thoracic operations were performed. Capacity, demographic, risk, quality, outcome and economic data were prospectively collected in various registries and analysed. Mean (and median) age increased from 64.2 to 65.3 (66-67). Patients above 70 years increased from 33.6 to 38.7% and above 80 from 2.9 to 5.5%. Operative mortality was unchanged over the time periods at slightly over 2%, with 1-year mortality 6-7%. Mortality for primary, elective coronary artery bypass grafting was 0.26% during the last 3 years. The rate of postoperative complications remained unchanged or decreased with few exceptions: Patients with postoperative confusion increased from 5.0 to 8.1% and patients with a need for face mask ventilation increased from 2.4 to 4.0%. Mean postoperative ventilation time was unchanged at around 22 h, whereas the median decreased from 9.5 to 5.3 h. The workload created by elderly patients was especially noticeable in the intensive care unit (ICU) as both number of postoperative deviations and ICU hours increased as a function of age. Cost per operation decreased by 11%. Total medical rationalisation was higher as salaries increased over time. Mean length of stay decreased by 3 days. Hospital staff hours per operation decreased whereas hospital staff hours per patient hour increased. Physician cost per operation was unchanged. Patient, staff and referring physician satisfaction was high. Several areas for improvement have been found. Monitoring and general feedback of total quality factors has shown itself a powerful tool to detect and follow large and subtle changes in the practice of cardio-thoracic surgery. Most followed factors show improvement in spite of an increase in mean and median age. Several areas may be defined where further development might decrease the trauma to the patient. Aiming at a total quality and patient safety system, monitoring is an essential prerequisite.

  • 928.
    Åden Bygdell, Simon
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    PSA-density; usefulness in lowering the numbers diagnosed with low risk prostate cancer2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 929.
    Åhman, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine.
    Saveman, Britt-Inger
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Styrke, Johan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Björnstig, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stålnacke, Britt-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine.
    Long-term follow-up of patients with mild traumatic brain injury: a mixed-methods study2013In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 45, no 8, p. 758-764Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To characterize the long-term consequences of mild traumatic brain injury regarding post-concussion symptoms, post-traumatic stress, and quality of life; and to investigate differences between men and women.

    DESIGN: Retrospective mixed-methods study.Subjects/patients and methods: Of 214 patients with mild traumatic brain injury seeking acute care, 163 answered questionnaires concerning post-concussion symptoms (Rivermead Post-Concussion Symptoms Questionnaire; RPQ), post-traumatic stress (Impact of Event Scale; IES), and quality of life (Short Form Health Survey; SF-36) 3 years post-injury. A total of 21 patients underwent a medical examination in connection with the survey. The patients were contacted 11 years later, and 10 were interviewed. Interview data were analysed with content analysis.

    RESULTS: The mean total RPQ score was 12.7 (standard deviation; SD 12.9); 10.5 (SD 11.9) for men and 15.9 (SD 13.8) for women (p = 0.006). The 5 most common symptoms were fatigue (53.4%), poor memory (52.5%), headache (50.9%), frustration (47.9%) and depression (47.2%). The mean total IES score was 9.6 (SD 12.9) 7.1 (SD 10.3) for men and 13.0 (SD 15.2) for women (p = 0.004). In general, the studied population had low scores on the Short Form Health Survey (SF-36). The interviews revealed that some patients still had disabling post-concussion symptoms and consequences in many areas of life 11 years after the injury event.

    CONCLUSION: Long-term consequences were present for approximately 50% of the patients 3 years after mild traumatic brain injury and were also reported 11 years after mild traumatic brain injury. This needs to be taken into account by healthcare professionals and society in general when dealing with people who have undergone mild traumatic brain injury.

  • 930.
    Åkesson, Oscar
    et al.
    Dept of Clinical Scienses, Lund University.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Blind, Per-Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Surface microdialysis on small bowel serosa in monitoring of ischemia2016In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 204, no 1, p. 39-46Article in journal (Refereed)
    Abstract [en]

    Background: Ischemic injury of an organ causes metabolic change from aerobic to anaerobic metabolism. It has been shown in experimental studies on the heart and liver that such conversion may be detected by conventional microdialysis probes placed intraparenchymatously, as well as on organ surfaces, by assaying lactate, pyruvate, glucose, and glycerol in dialysate. We developed a microdialysis probe (S-mu D) intended for use solely on organ surfaces. The aim of this study was to assess whether the newly developed S-mu D probe could be used for detection and monitoring of small bowel ischemia. Methods: In anesthetized normoventilated pigs, a control S-mu D probe was applied on the jejunal serosa 50 cm downstream from the duodenojejunal junction (DJJ). Starting 100 cm from DJJ, a 100-cm long ischemic segment was created by division of all mesenteric vessels. S-mu Ds were applied at 2.5, 5, 20, and 50 cm from the starting point of ischemia by serosal sutures. A standard mu D probe was placed in the abdominal cavity as a further control. Dialysate was harvested before inducing ischemia and subsequently every 20 min for 4 h. Central venous blood was drawn every hour to monitor systemic lactate, C-reactive protein, and white blood cell count. Results: Microdialysis lactate levels were significantly higher than baseline from 20 min on into protocol time in the ischemic segment and in the control S-mu D probe. The peritoneal cavity probe showed no significant elevation. Lactate levels from the ischemic segment reached a plateau at 60 min. Courses of pyruvate, glucose, and glycerol levels were in accordance with transition from an aerobic to anaerobic metabolism in the bowel wall. No statistically significant changes in hemoglobin, white blood cell count, or lactate values in central venous blood were recorded. Conclusions: Assaying the aforementioned compounds in dialysate, harvested by the newly developed S-mu D probe, allowed detection and monitoring of small bowel ischemia from 20 min on following its onset.

  • 931.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Prognostic factors in colorectal cancer: aspects of tumour dissemination2002Doctoral thesis, comprehensive summary (Other academic)
  • 932.
    Öberg, Åke
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Höyhtyä, Matti
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lindmark, Gudrun
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Limited value of preoperative serum analyses of matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitors of matrix metalloproteinases (TIMP-1, TIMP-2) in colorectal cancer2000In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 20, no 2B, p. 1085-1091Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We studied whether preoperative serum levels of free MMP-2, the MMP-2/TIMP-2 complex, and total amounts of MMP-9, TIMP-1 and TIMP-2 correlated to the tumor stage and prognosis in colorectal cancer.

    METHODS: Samples from 158 patients operated on for colorectal cancer (100 colon, 58 rectum) and samples from 80 healthy blood donors were analyzed using an ELISA technique. One hundred and thirty-three patients were resected for cure, (31, 61, and 41 in Dukes' stages A, B, and C, respectively). At follow-up in January 1998, 44 patients had died from their cancer after a median time 14 months (range 2-55). Fifteen patients died without tumor relapse. Ninety-nine patients were alive after, a median time of 46 months (range 17-68).

    RESULTS: Wide, overlapping ranges were observed for all factors both in the patients and in the control group. The patients as compared to the control group had significantly higher levels of free MMP-2 and total amounts of MMP-9, TIMP-1 and TIMP-2, whereas the level of the MMP-2/TIMP-2 complex was significantly lower. TIMP-1 was significantly higher in Dukes' D compared to Dukes' A-C cases; the other factors did not correlate to tumor stage. Elevated TIMP-2 levels (median cut-off limit), only, correlated to worse prognosis when analysed in all patients (p < 0.05). None of the factors (median cut-off limit) correlated to survival in Dukes' A-C patients; analyses based on the upper quartile cut-off limit demonstrated that elevated MMP-2 levels correlated to shorter survival time (p < 0.05).

    CONCLUSION: Serum analyses of free MMP-2 the MMP-2/TIMP-2 complex and total amounts of MMP-9, TIMP-1 and TIMP-2 are of limited value for tumor staging and prognosis in colorectal cancer.

  • 933.
    Öberg, Åke
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindmark, Gudrun
    Department of Surgery, Helsingborgs Lasarett, Lund University, Helsingborg, Sweden.
    Israelsson, Anne CE
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten G
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Marie-Louise KC
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR for CEA and CK20 mRNAS2004In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 111, no 1, p. 101-110Article in journal (Refereed)
    Abstract [en]

    The purpose of our study was to develop specific, sensitive, objective assays for early detection of disseminated tumour cells in patients with colorectal cancer (CRC). Carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) were chosen as markers because they are selectively expressed in epithelial cells with maintained expression in CRC. Real-time quantitative RT-PCR assays with RNA copy standards were constructed. Regional lymph nodes were collected from patients with CRC (n = 51) and benign intestinal disease (n = 10). Results were compared to routine histopathology and anti-CEA immunohistochemistry. Lymph node levels of CEA and CK20 mRNA correlated strongly (p < 0.0001, r = 0.8). Lymph nodes from non-CRC patients had <0.01 CEA and <0.001 CK20 mRNA copies/18S rRNA unit. Lymph nodes from 3/6 Dukes' A, 17/26 Dukes' B, 10/10 Dukes' C and 7/9 Dukes' D patients had CEA mRNA levels above cut-off. Corresponding figures for CK20 mRNA were 3/6, 10/26, 9/10 and 5/9, respectively. CEA mRNA levels varied from 0.001 to 100 copies/18S rRNA unit in Dukes' A and B, and 50% of the Dukes' B patients had CEA mRNA levels within the range of Dukes' C patients. Three Dukes' B patients have died from CRC or developed distant metastases. All 3 had high CEA and CK20 mRNA levels. Determination of mRNA was superior to immunohistochemistry in showing CEA expression in lymph nodes. The present qRT-PCR assay for CEA mRNA seems to be a superior tool to identify individuals with disseminated tumour cells. Future extended studies will establish the clinically most relevant cut-off level.

  • 934.
    Öberg, Åke
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Samii, S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lindmark, Gudrun
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Different occurrence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases from colorectal cancer as potential prognostic predictors2002In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 17, no 1, p. 25-29Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: To study whether there are differences in the immunohistochemical staining of CD8, CD45R0, and CD68 of immune cells in regional lymph node metastases from colorectal cancer that are of potential interest in prognostic prediction.

    MATERIALS AND METHODS: Analysis of archival specimens from 93 patients operated on for colorectal cancer (based on monoclonal antibodies, the ABC technique, and semiquantitative classification).

    RESULTS: There was a significant difference in survival time between patients with respect to the number of positive immune cells. The cancer-specific 5-year survival rate was 77% for patients with high numbers of CD8+ cells, compared to 33% for those with lower numbers. The corresponding figures for patients with CD45R0+ cells were 66% vs. 33%, and for patients with CD68+ cells 60% vs. 38%. Significant differences remained among the 74 patients without adjuvant radio/chemotherapy regarding CD8 and CD45R0 but not CD68.

    CONCLUSION: The presence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases may serve as predictors of patients survival in colorectal cancer Dukes' stage C.

  • 935.
    Öberg, Åke
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindmark, Gudrun
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Are lymph node micrometastases of any clinical significance in Dukes' stages A and B colorectal cancer?1998In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 41, no 10, p. 1244-1249Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim was to investigate the significance of lymph node micrometastases in Dukes Stages A and B colorectal cancer.

    METHODS: Archival specimens were examined from 147 patients (96 colon, 51 rectum; 44 Stage A, 103 Stage B) who had surgery between 1987 and 1994. One lymph node section from each node (colon, 1-11; median, 4; rectum, 1-15; median, 3) was examined with use of an anticytokeratin antibody.

    RESULTS: Forty-seven (32 percent) patients had micrometastases. At follow-up in June 1996, 23 patients had died of cancer or with known tumor relapse, after a median time of 28 (range, 5-67) months; 8 of 47 (17 percent) patients had micrometastases, 15 of 100 (15 percent) did not. No statistically significant differences were observed according to micrometastases when the results were analyzed with respect to Dukes stage or survival time. The median survival time of living patients with micrometastases was 48 (range, 18-97) months, and for patients without micrometastases, 48 (range, 19-111) months. Six of 96 living patients had a tumor relapse; three of these displayed micrometastases.

    CONCLUSION: Lymph node micrometastases are not a useful prognostic marker in Dukes Stages A and B and do not imply different strategies for additional therapy or follow-up.

  • 936.
    Ödling Davidsson, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Johagen, Daniel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Appelblad, Micael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Svenmarker, Staffan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Reversal of Heparin After Cardiac Surgery: Protamine Titration Using a Statistical Model2015In: Journal of Cardiothoracic and Vascular Anesthesia, ISSN 1053-0770, E-ISSN 1532-8422, Vol. 29, no 3, p. 710-714Article in journal (Refereed)
    Abstract [en]

    Objective: To establish a statistical model for determination of protamine dose in conjunction with cardiopulmonary bypass. Design: Prospective.

    Setting: University hospital.

    Participants: Ninety consecutive cardiac surgical patients.

    Interventions: None.

    Measurements and Main Results: A series of clinically oriented variables were introduced into a statistical model for projection of the protamine dose after cardiopulmonary bypass. The following significant predictors were identified using multivariable regression analysis: The patient's body surface area, the administered dose of heparin, heparin clearance, and the preoperative platelet count. The statistical model projected the protamine dose within 3 +/- 23 mg of the point-of-care test used as reference.

    Conclusion: Protamine dosing based on statistical modeling represents an alternative to point-of-care tests.

  • 937.
    Öhlund, Daniel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Basement membrane collagens in pancreatic cancer: novel stroma-derived tumor markers and regulators of cancer cell growth2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Among the common malignancies, pancreatic cancer has the shortest long-term survival. The aggressive, rapid, and infiltrative growth pattern of pancreatic cancer, together with the lack of specific symptoms, often leads to late diagnosis. Metastases are frequently found at the time of diagnosis, which prevents curative surgical treatment. Good tumor markers would enable early detection, thus improving the prognosis. Unfortunately, no such markers are available in the clinic.

    The tumor stroma is defined as the non-malignant cells and the extracellular matrix (ECM) of a cancer. Pancreatic cancer is characterized by an abundant tumor stroma, rich in ECM proteins such as collagens, which have been shown to play important roles in tumor progression. Furthermore, pancreatic cancer cells produce large quantities of ECM proteins, especially the basement membrane (BM) protein type IV collagen. All epithelial cells are anchored to a BM, which must be degraded in order for an in situ cancer to become invasive. Matrix metalloproteinases (MMPs) are enzymes involved in BM degradation.

    In this thesis, the tumor stroma of pancreatic cancer is studied, focusing on the BM proteins type IV and type XVIII collagen, with the aim to clarify if the stroma could be a source of novel tumor markers for this form of cancer. Additionally, the role of type IV collagen produced by the cancer cells is studied.

    Methods: Expression patterns of type IV and type XVIII collagen, MMPs involved in collagen degradation, and collagen receptors (integrins) were studied by immunoflourescence in both normal and pancreatic cancer tissue, and in pancreatic cancer cell lines. Circulating plasma levels of type IV and type XVIII collagen and conventional tumor markers (TPS, Ca 19-9, CEA and Ca 125) were measured in controls and pancreatic cancer patients at the time of diagnosis and after treatment.

    The role of cancer cell produced type IV collagen was studied in human pancreatic cancer cell lines by functional blocking of integrin receptors (integrin a1, a2 and b1) and integrin-binding sites on type IV collagen, and by siRNA-induced down-regulation of type IV collagen synthesis. Proliferation was analyzed by a luminescence based cell viability assay, migration by time-lapse microscopy, and apoptosis by M30-neoepitope detection.

    Results: MMPs involved in BM degradation were upregulated in pancreatic cancer tissue. The expression of type XVIII collagen shifted from a general BM expression pattern in normal tissue, to mainly being found in the tumor vasculature in pancreatic cancer. Type IV collagen, on the other hand, remained highly expressed in the vicinity of the cancer cells. The a1, a2, and b1 integrin receptors were highly expressed at the cancer cell surface.

    Both down-regulation of type IV collagen synthesis and blocking the integrin/type IV collagen interaction decreased cell proliferation and migration. The proliferative capacity was rescued by the addition of exogenous type IV collagen.

    Furthermore, the circulating levels of both type IV and type XVIII collagen were increased in pancreatic cancer patients at the time of diagnosis compared to controls. After treatment, the levels were normalized for type XVIII collagen, whereas the levels of type IV collagen remained high after surgery. High postoperative levels of type IV collagen were associated with short overall survival. A similar association to short survival was found for preoperative type XVIII collagen levels. No such associations to survival could be detected for the conventional markers.

     

    Conclusion: The results of this thesis show that type IV and type XVIII collagens can serve as tumor markers for pancreatic cancer with advantages compared to conventionally used markers. Additionally, evidence is provided of an autocrine loop, involving type IV collagen and its integrin receptors, with importance for retaining a proliferative and migratory phenotype in pancreatic cancer cells.

  • 938.
    Öhlund, Daniel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Cold Spring Harbor Laboratory and Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724.
    Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer2017In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 214, no 3, p. 579-596Article in journal (Refereed)
    Abstract [en]

    Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs with distinct phenotypes in PDA exist. We identified a CAF subpopulation with elevated expression of a-smooth muscle actin (alpha SMA) located immediately adjacent to neoplastic cells in mouse and human PDA tissue. We recapitulated this finding in co-cultures of murine PSCs and PDA organoids, and demonstrated that organoid-activated CAFs produced desmoplastic stroma. The co-cultures showed cooperative interactions and revealed another distinct subpopulation of CAFs, located more distantly from neoplastic cells, which lacked elevated aSMA expression and instead secreted IL6 and additional inflammatory mediators. These findings were corroborated in mouse and human PDA tissue, providing direct evidence for CAF heterogeneity in PDA tumor biology with implications for disease etiology and therapeutic development.

  • 939.
    Öhlund, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ardnor, Bjarne
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öman, Mikael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Expression pattern and circulating levels of endostatin in patients with pancreas cancer2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 122, no 12, p. 2805-2810Article in journal (Refereed)
    Abstract [en]

    Endostatin is a potent inhibitor of angiogenesis that is cleaved from the basement membrane protein type XVIII collagen. Expression of endostatin has recently been shown by Western blot analysis of tissue lysates in normal pancreas and pancreas cancer tissue. We show here that the expression pattern of type XVIII collagen/endostatin is shifted from a general basement membrane staining and is mainly located in the vasculature during tumor progression. This shift in type XVIII collagen/endostatin expression pattern coincides with an up-regulation of MMPs involved in endostatin processing in the tumor microenvironment, such as MMP-3, MMP-9 and MMP-13. The circulating levels of endostatin was analyzed in patients with pancreas cancer and compared to that of healthy controls, as well as after surgical treatment or in a group of nonoperable patients after intraperitoneal fluorouracil (5-FU) chemotherapy. The results show that patients with pancreas cancer have increased circulating levels of endostatin and that these levels are normalized after surgery or intraperitoneal chemotherapy. These findings indicate that endostatin could be used as a biomarker for pancreas cancer progression.

  • 940.
    Öhlund, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Franklin, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundberg, Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Type IV collagen enhances pancreatic cancer cell proliferation and migration through an autocrine loopManuscript (preprint) (Other academic)
  • 941.
    Öhlund, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Franklin, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundberg, Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Type IV collagen stimulates pancreatic cancer cell proliferation, migration, and inhibits apoptosis through an autocrine loop2013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, article id 154Article in journal (Refereed)
    Abstract [en]

    Background: Pancreatic cancer shows a highly aggressive and infiltrative growth pattern and is characterized by an abundant tumor stroma known to interact with the cancer cells, and to influence tumor growth and drug resistance. Cancer cells actively take part in the production of extracellular matrix proteins, which then become deposited into the tumor stroma. Type IV collagen, an important component of the basement membrane, is highly expressed by pancreatic cancer cells both in vivo and in vitro. In this study, the cellular effects of type IV collagen produced by the cancer cells were characterized.

    Methods: The expression of type IV collagen and its integrin receptors were examined in vivo in human pancreatic cancer tissue. The cellular effects of type IV collagen were studied in pancreatic cancer cell lines by reducing type IV collagen expression through RNA interference and by functional receptor blocking of integrins and their binding-sites on the type IV collagen molecule.

    Results: We show that type IV collagen is expressed close to the cancer cells in vivo, forming basement membrane like structures on the cancer cell surface that colocalize with the integrin receptors. Furthermore, the interaction between type IV collagen produced by the cancer cell, and integrins on the surface of the cancer cells, are important for continuous cancer cell growth, maintenance of a migratory phenotype, and for avoiding apoptosis.

    Conclusion: We show that type IV collagen provides essential cell survival signals to the pancreatic cancer cells through an autocrine loop.

  • 942.
    Öhlund, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ardnor, Bjarne
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öman, Mikael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer2009In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 101, no 1, p. 91-97Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients.

    METHODS: The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques.

    RESULTS: Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival.

    CONCLUSION: Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context.

  • 943.
    Öhlund, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öman, Mikael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Basement membrane fragments as pancreatic tumour markers: a comparison to conventional markersManuscript (preprint) (Other academic)
  • 944.
    Öman, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Fredriksson, Rikard
    Bylund, Per-Olof
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Björnstig, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Analysis of the mechanism of injury in non-fatal vehicle-to-pedestrian and vehicle-to-bicyclist frontal crashes in Sweden2016In: International Journal of Injury Control and Safety Promotion, ISSN 1745-7300, E-ISSN 1745-7319, Vol. 23, no 4, p. 405-412Article in journal (Refereed)
    Abstract [en]

    The aim of this paper is to analyse and compare injuries and injury sources in pedestrian and bicyclist non-fatal real-life frontal passengercar crashes, considering in what way pedestrian injury mitigation systems also might be adequate for bicyclists. Data from 203 non-fatal vehicle-to-pedestrian and vehicle-to-bicyclist crashes from 1997 through 2006 in a city in northern Sweden were analysed by use of the hospitals injury data base in addition to interviews with the injured. In vehicle-to-pedestrian crashes (n = 103) head and neck injuries were in general due to hitting the windscreen frame, while in vehicle-to-bicycle crashes (n = 100) head and neck injuries were typically sustained by ground impact. Abdominal, pelvic and thoracic injuries in pedestrians and thoracic injuries in bicyclists were in general caused by impacting the bonnet. In vehicle-to-pedestrian crashes, energy reducing airbags at critical impact points with low yielding ability on the car, as the bonnet and the windscreen frame, might reduce injuries. As vehicle-to-bicyclist crashes occurred mostly in good lighting conditions and visibility and the ground impact causing almost four times as many injuries as an impact to the different regions of the car, crash avoidance systems as well as separating bicyclists from motor traffic, may contribute to mitigate these injuries.

  • 945.
    Öman, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundqvist, Stefan
    Gustavsson, Bengt
    Hafström, Lars-Olof
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous Vasopressin in non-resectable pancreatic cancer2005In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 56, no 6, p. 603-609Article in journal (Refereed)
    Abstract [en]

    Background: Systemic palliative treatment with chemotherapy against advanced pancreas cancer has low effectiveness despite considerable toxicity. Aim: To investigate the safety, toxicity and tumour response of intraperitoneal 5-Fluorouracil (5-FU) with intravenous Leucovorin and to monitor 5-FU pharmacokinetics in plasma during intraperitoneal instillation with and without vasopressin in patients with non-resectable pancreas cancer. Patients/methods: Between 1994 and 2003, 68 patients with non-resectable pancreas cancer TNM stage III and IV, were enrolled to receive intraperitoneal 5-FU instillation 750–1500 mg/m2 and intravenous Leucovorin 100 mg/m2 for two days every third week. Tumour response, performance status and toxicity were recorded. Seventeen patients were also treated with intravenous vasopressin 0.1 IU/minute for 180 minutes, during intraperitoneal 5-FU instillation. Area under the curve (AUC) and peak concentration (Cmax) of 5-FU in plasma were analysed. Results: The treatment was well tolerated with minor toxicity. One complete response (54.1+ months) and 2 partial responses were observed. Time to progression was 4.4 months (0.8–54.1+), and median survival was 8.0 months (0.8–54.1+). There was a significant reduction of 5-FU Cmax in plasma the second day of treatment if vasopressin was used (3.4 ± 2.5 and 6.1 ± 5.4 μmol/l, respectively, p<0.05). 5-FU AUC in plasma was not significantly affected by vasopressin either day of treatment. Conclusion: Intraperitoneal 5-FU is a safe treatment with low toxicity to patients with non-resectable pancreas cancer. Tumour response was 4.4% and median survival time 8.0 months. Addition of vasopressin did not significantly decrease plasma 5-FU AUC but reduced Cmax on day 2 of treatment.

  • 946.
    Öman, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Tölli, Jukka
    Blind, Per-Jonas
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Hafström, Lars-Olof
    133Xe clearance estimates the effect of vasopressin on peritoneal blood flow in rats2004In: Hepato-Gastroenterology, ISSN 0172-6390, Vol. 51, no 58, p. 1037-1041Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: When assessing the peritoneal microcirculation with invasive methods, interference with the mechanisms of vaso-regulation may occur. The 133Xe clearance technique renders the possibility, by minimal invasiveness, to estimate the influence of a vasoactive agent on the peritoneal microcirculation. METHODOLOGY: Ten to 15MBq of 133Xe were injected in the abdominal cavity in thirty-eight Wistar-FU (W-FU) rats and 35 Lister-Hooded (LH) rats. A NaI (Tl)-scintillation detector registered activity before and during vasopressin infusion. Gamma camera imaging confirmed the washout from the abdominal cavity. The laser Doppler flowmetry technique was used as a comparison. RESULTS: Vasopressin at 0.07 IU/kg/min IV significantly reduced 133Xe-clearance by 37% (p = 0.029) and 52% (p=0.036) and laser Doppler flowmetry by 69% (p=0.0019) and 44% (p=0.0039) in W-FU and LH rats, respectively. A linear correlation between dose of vasopressin and relative decrease in 133Xe clearance was demonstrated in the W-FU rat model (r2=0.98, p=0.023). The 133Xe clearance from the abdominal cavity in rat using a single-compartment model or the slow compartment in a double-compartment model gave reproducible information. CONCLUSIONS: The usefulness of this mini-invasive technique for sequential measurements before and during intervention will render the 133Xe clearance suitable for assessment of blood flow changes in the abdominal cavity.

  • 947.
    Öman, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Tölli, Jukka
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Hafström, Lars-Olof
    Effect of carcinomatosis and intraperitoneal 5-fluorouracil on peritoneal blood flow modulated by vasopressin in the rat as measured with the 133Xe-clearance technique2004In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 54, no 3, p. 213-218Article in journal (Refereed)
    Abstract [en]

    Purpose: Intraperitoneal administration of 5-fluorouracil for the treatment of gastrointestinal malignancies results in a greater total drug exposure in the peritoneal fluid than in plasma. Drugs are eliminated from the peritoneal cavity mainly by capillaries leading to the portal venous system and to a lesser extent by lymphatics. The drug itself and the presence of peritoneal carcinomatosis may affect elimination of the drug. The 133Xe-clearance technique allows the influence of a vasoactive agent on the peritoneal blood flow to be estimated with minimal invasiveness. The aim of the present study was to explore whether intraperitoneal 5-FU or peritoneal carcinomatosis affects the peritoneal blood flow and its reactivity to intravenous vasopressin, as measured indirectly with the 133Xe-clearance technique. Methods: The animals used in this study were 63 Wistar-Fu (W-Fu) rats and 67 Lister-Hooded (LH) rats. On day 0, either 5-FU at 25 mg/kg body weight in 25 ml/kg isotonic saline was instilled intraperitoneally, or 1·105 syngeneic tumour cells were inoculated intraperitoneally. On days 1, 2 and 3 in the 5-FU-treated rats, and on days 12–16 in rats inoculated with tumour cells, peritoneal blood flow was analysed with the 133Xeclearance technique, before and during intravenous infusion of vasopressin at 0.07 IU/min/kg body weight. Results: The basal 133Xe-clearance before administration of vasopressin was similar in all groups except in the LH rats treated with 5-FU in which it was significantly lower. Infusion of vasopressin induced a significant decrease in 133Xe-clearance of the same magnitude in controls and in tumour-bearing rats. In the rats given intraperitoneal 5-FU, vasopressin did not reduce the 133Xe-clearance the first day after administration of 5-FU. Conclusions: Intravenous vasopressin at 0.07 IU/ min/kg decreased peritoneal blood flow as measured indirectly with the 133Xe-clearance method. Intraperitoneal 5-FU abrogated the reduction in peritoneal blood flow with intravenous vasopressin the first day after treatment. In contrast, the presence of peritoneal carcinomatosis did not influence peritoneal blood flow, nor the effect of vasopressin

  • 948.
    Österlund, Barbro
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Andersson, Bengt
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Jern, Christina
    Johansson, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Seeman-Lodding, Helen
    Biber, Björn
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Myocardial ischemia induces coronary t-PA release in the pig2002In: Acta Anaesthesiol Scand, Vol. 46, no 3, p. 271-8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tissue-type plasminogen activator (t-PA) is the key factor in initiating endogenous fibrinolysis in the vascular compartment. Regulated release of t-PA from endothelial stores is rapidly induced by several humoral factors as well as coagulation activation products. The aim of the present study was to test the hypothesis that regional myocardial ischemia induces regulated release of t-PA in the coronary vasculature in vivo. METHODS: Healthy anesthetized (pentobarbital) pigs (n=8) were studied before and after a 10-min left anterior descending region coronary artery occlusion (LAD). Coronary fluxes of lactate, total t-PA antigen (ELISA, detecting both complex bound and free fraction) and active t-PA (functional assay detecting biological free fraction) were determined at 1, 3, 5 and 10 min of reflow. RESULTS: Coronary occlusion induced myocardial lactate production in all animals. Net coronary release of total t-PA, which was 21 ng/min during control, increased rapidly during reflow with a peak after only 1 min (136 ng/min), and returned to baseline within 3 min. Net release of active t-PA mirrored the overall net release response, but fell short of statistical significance. CONCLUSION: Data indicate a local myocardial profibrinolytic response following regional ischemia, which may serve as a prompt defence against coronary thromboembolic events.

  • 949.
    Österlund, Barbro
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Surgery.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Jern, Christina
    Johansson, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Seeman-Lodding, Helen
    Biber, Björn
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Surgical stress induces acute coronary release of tissue-type plasminogen activator in the pig2000In: Acta Anaesthesiol Scand, Vol. 44, no 10, p. 1226-31Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tissue-type plasminogen activator (t-PA) is an endothelium derived key enzyme in the initiation of endogenous fibrinolysis. Acute regulated release of active t-PA occurs within minutes in response to threatening thrombotic vessel occlusion. The aim of this study was to investigate the impact of surgical stimulation on the kinetics of t-PA release in the coronary vascular bed in the pig. METHODS: In anaesthetised pigs (n=16), arterio-venous concentration gradients of t-PA, and plasma flows (retrograde thermodilution) were obtained across the coronary vascular bed before (control) and at 1, 3, 5 and 10 min after sternotomy. RESULTS: At control, no significant coronary net flux (release or uptake) of t-PA was observed, while sternotomy induced a rapid net release of total t-PA (132.6 ng x min(-1)), with an associated increase in active t-PA (93.6 ng x min(-1)). This response, evident already after 1 min, showed a peak at 5 min and returned towards baseline levels within 10 min. No concurrent alterations in aortic levels of active t-PA were found and haemodynamic variables were unaltered. CONCLUSION: The rapidly increasing and transient net coronary release of t-PA after sternotomy suggests that the endothelium actively promotes local endogenous fibrinolysis during surgery. Such events could reflect a dynamic responsiveness to protect the coronary circulation during stress.

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