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  • 751. Zetlitz, Elisabeth
    et al.
    Wearing, Scott Cameron
    Nicol, Alexander
    Mackay Hart, Andrew
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Objective Assessment of Surgical Training in Flexor Tendon Repair: The Utility of a Low-Cost Porcine Model as Demonstrated by a Single-Subject Research Design2012In: Journal of Surgical Education, ISSN 1931-7204, Vol. 69, no 4, p. 504-510Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study evaluated the utility of a porcine flexor tendon model and standard biomechanical testing procedures to quantify the acquisition of surgical skills associated with Zone II flexor tendon repair in a trainee by benchmarking task performance outcomes relative to evidence-based standards. STUDY DESIGN: Single-subject repeated measures research design. Bench-top set-up of apparatus undertaken in a University Research laboratory. After initial directed learning, a trainee repaired 70 fresh flexor digitorum profundus tendons within the flexor sheath using either a Pennington or ventral-locking-loop modification of a two-strand Kessler core repair. Tendon repairs were then preconditioned and distracted to failure. Key biomechanical parameters of the repair, including the ultimate tensile strength (UTS), yield strength, 3 mm gap force and stiffness, were calculated. Repairs were divided into 3 categories, early (first 10 days), intermediate (ensuing 10 days), and late repairs (final 10 days), and potential changes in repair properties over the training period were evaluated using a general linear modeling approach. RESULTS: There was a significant change in the mechanical characteristics of the repairs over the training period, evidencing a clear learning effect (p < 0.05). Irrespective of the repair technique employed, early and intermediate repairs were characterized by a significantly lower UTS (29% and 20%, respectively), 3 mm gap (21% and 16%, respectively), and yield force (18% and 23%, respectively), but had a higher stiffness (33% and 38%, respectively) than late repairs (p < 0.05). The UTS of late repairs (47-48 N) were comparable to those published within the literature (45-51 N), suggesting surgical competence of the trainee. CONCLUSIONS: This simple, low-cost porcine model appears to be useful for providing preclinical training in flexor tendon repair techniques and has the potential to provide a quantitative index to evaluate the competency of surgical trainees. Further research is now required to identify optimal training parameters for flexor tendon repair and to develop procedure-specific standards for adequate benchmarking.

  • 752. Zhang, Cheng-Gang
    et al.
    Welin, Dag
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Novikov, Lev
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kellerth, Jan-Olof
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Hart, Andrew McKay
    Motorneuron protection by N-acetyl-cysteine after ventral root avulsion and ventral rhizotomy2005In: British Journal of Plastic Surgery, ISSN 0007-1226, E-ISSN 1465-3087, Vol. 58, no 6, p. 765-773Article in journal (Refereed)
    Abstract [en]

    Motor recovery after proximal nerve injury remains extremely poor, despite advances in surgical care. Several neurobiological hurdles are implicated, the most fundamental being extensive cell death within the motorneuron pool. N-acetyl-cysteine almost completely protects sensory neurons after peripheral axotomy, hence its efficacy in protecting motorneurons after ventral root avulsion/rhizotomy was investigated. In adult rats, the motorneurons supplying medial gastrocnemius were unilaterally pre-labelled with retrograde tracer (true-blue/fluoro-gold), prior to L5 and 6 ventral root avulsion, or rhizotomy. Groups received either intraperitoneal N-acetyl-cysteine (ip, 150 or 750 mg/kg/day), immediate or delayed intrathecal N-acetyl-cysteine treatment (it, 2.4 mg/day), or saline; untreated animals served as controls. Either 4 (avulsion model) or 8 (rhizotomy model) weeks later, the pre-labelled motorneurons' mean soma area and survival were quantified. Untreated controls possessed markedly fewer motorneurons than normal due to cell death (avulsion 53% death; rhizotomy 26% death, P<0.01 vs. normal). Motorneurons were significantly protected by N-acetyl-cysteine after avulsion (ip 150 mg/kg/day 40% death; it 30% death, P<0.01 vs. no treatment), but particularly after rhizotomy (ip 150 mg/kg/day 17% death; ip 750 mg/kg/day 7% death; it 5% death, P<0.05 vs. no treatment). Delaying intrathecal treatment for 1 week after avulsion did not impair neuroprotection, but a 2-week delay was deleterious (42% death, P<0.05 vs. 1-week delay, 32% death). Treatment prevented the decrease in soma area usually found after both types of injury. N-acetyl-cysteine has considerable clinical potential for adjuvant treatment of major proximal nerve injuries, including brachial plexus injury, in order that motorneurons may survive until surgical repair facilitates regeneration.

  • 753.
    Zrinzo, Ludvic
    et al.
    UCL, UCL Inst Neurol, Unit Funct Neurosurg, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
    Foltynie, Thomas
    UCL, UCL Inst Neurol, Unit Funct Neurosurg, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
    Limousin, Patricia
    UCL, UCL Inst Neurol, Unit Funct Neurosurg, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Image-verified deep brain stimulation reduces risk and cost with no apparent impact on efficacy2012In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 27, no 12, p. 1585-1586Article in journal (Refereed)
  • 754. Zrinzo, Ludvic
    et al.
    Foltynie, Thomas
    Limousin, Patricia
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review Clinical article2012In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 116, no 1, p. 84-94Article, review/survey (Refereed)
    Abstract [en]

    Object. Hemorrhagic complications carry by far the highest risk of devastating neurological outcome in functional neurosurgery. Literature published over the past 10 years suggests that hemorrhage, although relatively rare, remains a significant problem. Estimating the true incidence of and risk factors for hemorrhage in functional neurosurgery is a challenging issue. Methods. The authors analyzed the hemorrhage rate in a consecutive series of 214 patients undergoing image-guided deep brain stimulation (DBS) lead placement without microelectrode recording (MER) and with routine postoperative MR imaging lead verification. They also conducted a systematic review of the literature on stereotactic ablative surgery and DBS over a 10-year period to determine the incidence and risk factors for hemorrhage as a complication of functional neurosurgery. Results. The total incidence of hemorrhage in our series of image-guided DBS was 0.9%: asymptomatic in 0.5%, symptomatic in 0.5%, and causing permanent deficit in 0.0% of patients. Weighted means calculated from the literature review suggest that the overall incidence of hemorrhage in functional neurosurgery is 5.0%, with asymptomatic hemorrhage occurring in 1.9% of patients, symptomatic hemorrhage in 2.1% and hemorrhage resulting in permanent deficit or death in 1.1%. Hypertension and age were the most important patient-related factors associated with an increased risk of hemorrhage. Risk factors related to surgical technique included use of MER, number of MER penetrations, as well as sulcal or ventricular involvement by the trajectory. The incidence of hemorrhage in studies adopting an image-guided and image-verified approach without MER was significantly lower than that reported with other operative techniques (p < 0.001 for total number of hemorrhages, p < 0.001 for asymptomatic hemorrhage, p < 0.004 for symptomatic hemorrhage, and p = 0.001 for hemorrhage leading to permanent deficit; Fisher exact test). Conclusions. Age and a history of hypertension are associated with an increased risk of hemorrhage in functional neurosurgery. Surgical factors that increase the risk of hemorrhage include the use of MER and sulcal or ventricular incursion. The meticulous use of neuroimaging-both in planning the trajectory and for target verification-can avoid all of these surgery-related risk factors and appears to carry a significantly lower risk of hemorrhage and associated permanent deficit. (DOI: 10.3171/2011.8.JNS101407)

  • 755. Zrinzo, Ludvic
    et al.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Errors of Image Coregistration may Necessitate Intraoperative Refinement in Functional Neurosurgery2013In: J NEUROL SURG PART A, ISSN 2193-6315, Vol. 74, no 5, p. 335-336Article in journal (Refereed)
  • 756. Zrinzo, Ludvic
    et al.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. UCL Institute of Neurology, University College London, London, United Kingdom.
    Hyam, Jonathan A.
    Foltynie, Thomas
    Limousin, Patricia
    A paradigm shift toward MRI-guided and MRI-verified DBS surgery2016In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 124, no 4, p. 1135-1137Article in journal (Refereed)
  • 757.
    Zrinzo, Ludvic
    et al.
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Yoshida, Fumiaki
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Thornton, John
    UCL Institute of Neurology and Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Foltynie, Thomas
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Yousry, Tarek A.
    UCL Institute of Neurology and Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK .
    Limousin, Patricia
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Clinical safety of brain magnetic resonance imaging with implanted deep brain stimulation hardware: large case series and review of the literature2011In: World Neurosurgery, ISSN 1878-8750, Vol. 76, no 1-2, p. 164-172Article in journal (Refereed)
    Abstract [en]

    Background: Over 75,000 patients have undergone deep brain stimulation (DBS) procedures worldwide. Magnetic resonance imaging (MRI) is an important clinical and research tool in analyzing electrode location, documenting postoperative complications, and investigating novel symptoms in DBS patients. Functional MRI may shed light on the mechanism of action of DBS. MRI safety in DBS patients is therefore an important consideration.

    Methods: We report our experience with MRI in patients with implanted DBS hardware and examine the literature for clinical reports on MRI safety with implanted DBS hardware.

    Results: A total of 262 MRI examinations were performed in 223 patients with intracranial DBS hardware, including 45 in patients with an implanted pulse generator. Only 1 temporary adverse event occurred related to patient agitation and movement during immediate postoperative MR imaging. Agitation resolved after a few hours, and an MRI obtained before implanted pulse generator implantation revealed edema around both electrodes. Over 4000 MRI examinations in patients with implanted DBS hardware have been reported in the literature. Only 4 led to adverse events, including 2 hardware failures, 1 temporary and 1 permanent neurological deficit. Adverse neurological events occurred in a unique set of circumstances where appropriate safety protocols were not followed. MRI guidelines provided by DBS hardware manufacturers are inconsistent and vary among devices.

    Conclusions: The importance of MRI in modern medicine places pressure on industry to develop fully MRI-compatible DBS devices. Until then, the literature suggests that, when observing certain precautions, cranial MR images can be obtained with an extremely low risk in patients with implanted DBS hardware.

  • 758.
    Ängquist, Karl-Axel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Human skeletal muscle fibre structure: effects of physical training and arterial insufficiency1978Doctoral thesis, comprehensive summary (Other academic)
  • 759.
    Åberg, Torkel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Defence, counterattack, retreat?2004In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 26, no Suppl 1, p. S32-S35Article in journal (Refereed)
    Abstract [en]

    Cardio-thoracic surgery is facing changes which are imposed upon us from two sources, medical development within cardiology and the general demographic and economic development of the western world. These two developments have to be faced. This treaty describes one way of thinking in our response to the changes. Using old strategic principles our options are attack, defence and retreat. The three options are described in some detail. In order to be well prepared, knowledge and preparation for all three options is necessary in meeting the challenges of the future.

  • 760.
    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.))
  • 761.
    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.

  • 762.
    Åkesson, Oscar
    et al.
    Institutionen för Klinisk Vetenskap, Lunds Universitet.
    Falkenback, Dan
    Institutionen för Klinisk Vetenskap, Lunds Universitet.
    Johansson, Göran
    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.
    Surface Microdialysis Detects Ischemia After Esophageal Resection: An Experimental Animal Study2019In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 245, p. 537-543Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: After an esophageal resection, continuity is commonly restored by a gastric tube reconstruction and an intrathoracic anastomosis to the remaining proximal esophagus. Ischemia of the anastomotic region is considered to play a pivotal role in anastomotic leakage. Microdialysis (μD) is an excellent method to measure local biochemical substances and parameters in a specific organ or compartment aiming at early detection of ischemia. This animal study evaluates ischemia of the gastric tube reconstruction using a novel method-μD on organ surfaces. This promising method may have the potential to detect an anastomotic leakage before clinical symptoms develop.

    METHODS: Anesthetized normoventilated pigs were used. Surface microdialysis (S-μD) catheters and an intraparenchymal oxygen tension catheter were placed on the stomach. A gastric tube was made and the gastroepiploic artery was divided halfway along the greater curvature to produce severe ischemia at the top of the gastric tube. μD data from four locations (gastric tube, ileum and peritoneal cavity) were recorded every 20 min during the experiment. Tissue samples from all catheter sites underwent histopathological analysis. Intraparenchymal oxygen partial pressure, systemic blood tests, and hemodynamic parameters were recorded.

    RESULTS: S-μD data showed values indicating severe ischemia at the top of the gastric tube and intermediate ischemia at the level of transection of the gastroepiploic artery. Ischemia was verified by histopathological analysis of tissue samples and intraparenchymal oxygen tension data.

    CONCLUSIONS: S-μD can detect and grade severity of local ischemia in real time, in an animal model.

  • 763. Åstrand, Per
    et al.
    Ahlqvist, Jan
    Umeå University, Faculty of Medicine, Department of Odontology, Oral and Maxillofacial Radiology.
    Gunne, Johan
    Umeå University, Faculty of Medicine, Department of Odontology, Prosthetic Dentistry.
    Nilsson, Hans
    Umeå University, Faculty of Medicine, Department of Odontology, Prosthetic Dentistry.
    Implant treatment of patients with edentulous jaws: a 20-year follow-up2008In: Clinical Implant Dentistry and Related Research, ISSN 1523-0899, E-ISSN 1708-8208, Vol. 10, no 4, p. 207-217Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Implant-supported prostheses are today often used in rehabilitation of partially or totally edentulous patients. Both patients and the dental profession often regard implant treatment as successful in a life perspective. Therefore, studies with a long-term follow-up are important.

    PURPOSE: The aim was to investigate the outcome of implant treatment with fixed prostheses in edentulous jaws after 20 years, with special reference to survival rate of implants and prostheses and frequency of peri-implantitis.

    MATERIALS AND METHODS: The patient material was a group of patients treated in the early 1980s. The original patient group comprised the first 48 consecutive patients treated with implant-supported prostheses at Umeå University. All patients were edentulous in one or two jaws. The patients had a mean age at the implant insertion of 54.3 years (range 40-74). At the planning of this study 20 years after treatment, 19 of the 48 patients were found to be deceased. Of the 29 patients still alive, 21 patients with altogether 23 implant-supported prostheses could be examined clinically and radiographically. All patients were treated ad modum Brånemark (Nobel Biocare AB, Göteborg, Sweden) with a two-stage surgical procedure. The implants had a turned surface. Abutment connections were performed 3 to 4 months after fixture insertion in the mandible, and after a minimum of 6 months in the maxilla. The prostheses were fabricated with a framework of gold alloy and acrylic artificial teeth.

    RESULTS: The 21 patients (with 23 implant prostheses) examined had at the time of treatment got 123 implants (27 in the upper jaw and 96 in the lower jaw) inserted. Only one of these implants had been lost (about 2 years after loading) giving a survival rate of 99.2%. Very small changes occurred in the marginal bone level. Between the 1 and 20-year examinations, the mean bone loss was 0.53 mm and the mean bone level at the final examination was 2.33 mm below the reference point.

    CONCLUSIONS: This follow-up over two decades of implant-supported prostheses demonstrates a very good prognosis for the treatment performed. The frequencies of peri-implantitis, implant failures, or other complications were very small, and the original treatment concept with a two-stage surgery and a turned surface of the implants will obviously give very good results.

  • 764. Åstrom, Mattias
    et al.
    Samuelsson, Jennifer
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Roothans, Jonas
    Fytagoridis, Anders
    Ryzhkov, Maxim
    Nijlunsing, Rutger
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Prediction of Electrode Contacts for Clinically Effective Deep Brain Stimulation in Essential Tremor2018In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 96, no 5, p. 281-288Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Deep brain stimulation (DBS) is an established neurosurgical treatment that can be used to alleviate symptoms in essential tremor (ET) and other movement disorders. The aim was to develop a method and software tool for the prediction of effective DBS electrode contacts based on probabilistic stimulation maps (PSMs) in patients with ET treated with caudal zona incerta (cZi) DBS. Methods: A total of 33 patients (37 leads) treated with DBS were evaluated with the Essential Tremor Rating Scale (ETRS) 12 months after surgery. In addition, hand tremor and hand function (ETRS items 5/6 and 11-14) were evaluated for every contact during stimulation with best possible outcome without inducing side effects. Prediction of effective DBS electrode contacts was carried out in a retrospective leave-one-out manner based on PSMs, simulated stimulation fields, and a scoring function. Electrode contacts were ranked according to their likelihood of being included in the clinical setting. Ranked electrode contacts were compared to actual clinical settings. Results: Predictions made by the software tool showed that electrode contacts with rank 1 matched the clinically used contacts in 60% of the cases. Contacts with a rank of 1-2 and 1-3 matched the clinical contacts in 83 and 94% of the cases, respectively. Mean improvement of hand tremor and hand function was 79 +/- 21% and 77 +/- 22% for the clinically used and the predicted electrode contacts, respectively. Conclusions: Effective electrode contacts can be predicted based on PSMs in patients treated with cZi DBS for ET. Predictions may in the future be used to reduce the number of clinical assessments that are carried out before a satisfying stimulation setting is defined.

  • 765. Åström, Mattias
    et al.
    Tripoliti, Elina
    Martinez-Torres, Irene
    Zrinzo, Ludvic U
    Limousin, Patricia
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Wårdell, Karin
    Patient-specific models and simulations of deep brain stimulation for postoperative follow-up2009In: World Congress on Medical Physics and Biomedical Engineering September 7 - 12, 2009 Munich, Germany: Vol. 25/9 Neuroengineering, Neural Systems, Rehabilitation and Prosthetics / [ed] Dössel, Olaf; Schlegel, Wolfgang C., Springer , 2009, p. 331-334Conference paper (Other academic)
  • 766.
    Öberg, Sven
    Umeå University, Faculty of Medicine, Department of Odontology.
    Bone Healing after implantation of bone substitute materials. Experimental studies in estrogen deficiency.2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Bone formation and bone healing were studied in the mandible, tibia and skull bones in adult, healthy and estrogen deficient rabbits implanted with different bone substitutes.

    In the first study an evaluation of the differences in bone regeneration in and around solid (Alveograf *) and porous hydroxyapatite (Interpore 200*) was undertaken. The implant material was placed into experimentally made bone defects and in half of the defects hydroxyapatite was mixed with a fibrin sealant (Tisseel *). The material alone or mixed with Tisseel was also placed subperiostally in the mandible. The observation time was six month. No difference in bone regeneration was found between solid or porous hydroxyapatite granulas and the addition of Tisseel* did not seem to disturb the bone healing process. The implant material placed subperiostally did not induce bone formation nor did it provoke any bone resorption. The addition of Tisseel made the implant material much easier to handle and retain in the tissue during surgery.

    Bone healing around hydroxyapatite implants was also evaluated in the second study. Experimental cavities in the mandible and tibia were filled with hydroxyapatite in granules or blocks (Interpore 200*) but now with or without autolyzed, antigen-extracted, allogeneic bone (AAA). Also in this study Tisseel* was used to facilitate the handling of the material. All cavities implanted with AAA-bone, regardless of the combination with hydroxyapatite or Tisseel, demonstrated excessive bone formation resembling exostosis formation. Thus, hydroxyapatite, both as granules and blocks, can be successfully combined with AAA bone utilizing the bone inductive capacity of AAA bone.

    The same model was used to study the healing in ovariectomized animals in the third study. Bone cavities were implanted with or without AAA bone and left to heal. The results indicate that the osteoinductive capacity of AAA bone is in operation also in animals deprived of a normal estrogen production.

    The effect of using AAA bone prior to implant insertion was studied in paper four. The bone-implant contact was significant higher when AAA bone had been used. The implant stability did not seem to be affected.

    In paper five defects were made in skull and tibial bone in estrogen deficient animals. The deficiency of estrogen was confirmed through blood analysis, the decrease in the weight of uterus and bone mineral density. The whole body scanning with DEXA showed that the ovariectomized animals developed osteopenia. Various degree of bone formation was seen in the defects due to the influence of the bone inductive substance AAA bone.

    The studies indicate that a conductive material like hydroxyapatite in granules or blocks could be useful in oral reconstructive surgery. The combination with AAA bone enhanced the bone formation in calvarial and tibial bone in healthy and estrogen deficient animals. Tisseel* could be used to facilitate handling and retention of the material in the intended position during the healing process without negative effects.

  • 767.
    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.

  • 768.
    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.

  • 769.
    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.

  • 770. Öhlund, Daniel
    et al.
    Elyada, Ela
    Tuveson, David
    Fibroblast heterogeneity in the cancer wound2014In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 211, no 8, p. 1503-1523Article, review/survey (Refereed)
    Abstract [en]

    Fibroblasts regulate the structure and function of healthy tissues, participate transiently in tissue repair after acute inflammation, and assume an aberrant stimulatory role during chronic inflammatory states including cancer. Such cancer-associated fibroblasts (CAFs) modulate the tumor microenvironment and influence the behavior of neoplastic cells in either a tumor-promoting or tumor-inhibiting manner. These pleiotropic functions highlight the inherent plasticity of fibroblasts and may provide new avenues to understand and therapeutically intervene in malignancies. We discuss the emerging themes of CAF biology in the context of tumorigenesis and therapy.

  • 771.
    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.

  • 772.
    Öman, Mikael
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Intraperitoneal 5-Fluorouracil treatment of cancer - clinical and experimental studies2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background:Pancreas cancer is a most aggressive malignancy. More than 80% of patients diagnosed with pancreas cancer, exhibit such advanced disease, that curative surgery is impossible. Systemic chemotherapy prolongs survival to 5-9 months. High concentrations of chemotherapeutic agents in the abdominal cavity and in the lymphatics draining the area is achieved by intraperitoneal administration. Vasopressin decreases splanchnic blood flow, reducing the intraperitoneal uptake of drugs, thus raising the local and lymphatic dose intensity.

    Aim: The aim of the study was to investigate the feasibility and tumour response of intraperitoneal 5-Fluorouracil (5-FU) treatment in non-resectable pancreas cancer, using vasopressin to improve the pharmacokinetic profile. Further, to study the effect of vasopressin on peritoneal blood flow, altered by intraperitoneal 5-FU or the presence of peritoneal carcinomatosis.

    Methods: In the animal experiments, the 133Xe-clearance technique and as a comparison Laser doppler flow, were used to identify changes of peritoneal blood flow caused by vasopressin in unmanipulated animals and in animals with peritoneal carcinomatosis or animals given intraperitoneal 5-FU. In the clinical studies, 68 (39 women/29 men) patients, with a non-resectable ductal pancreas cancer and a Karnovsky Index ≥70 were included. Patients were treated with 750-1500 mg/m2 5-FU intraperitoneally through a Port-a-cath and Leucovorin 100 mg/m2 intravenously on two consecutive days every 21 days until progression. Seventeen patients, receiving 750 mg/m2 5-FU, were given concomitant vasopressin 0.1 IU/min during 180 minutes, alternatively day 1 or 2.

    Results: In the animal experiments, vasopressin 0.07 IU/kg/min significantly reduced the 133Xe-clearance. Intraperitoneal 5-FU decreased the basal peritoneal blood flow and abrogated the vasopressin effect for 1-2 days. The presence of peritoneal carcinomatosis did not influence the basal peritoneal blood flow, nor the reduction of peritoneal blood flow caused by vasopressin. In the clinical studies, the treatment with intraperitoneal 5-FU was well tolerated, with no WHO Grade 3 or 4 toxicity with doses up to 1250 mg/m2. Thirty patients achieved at least stable disease at three months. The median survival time was 8.0 (range 0.8-54.1) months. There was a significant reduction of 5-FU Cmax on day 2, but no significant reduction of AUC, when vasopressin was given.

    Conclusion: Peritoneal blood flow changes caused by vasopressin can be estimated with the 133Xe-clearance technique. Intraperitoneal 5-FU but not peritoneal carcinomatosis decreases the vasopressin induced 133Xe-clearance reduction, 1-2 days after administration. In patients with non-resectable pancreas cancer, intraperitoneal 5-FU up to 1250 mg/m2 for two days every third week can be given without WHO grade 3 and 4 toxicity. The treatment is well tolerated with few and minor side effects. Tumour responses were observed. Addition of vasopressin does not significantly enhance the pharmacokinetics of intraperitoneal 5-Flurorouracil, but adds toxicity.

  • 773.
    GlobalSurg Collaborative, (Contributor)
    NIHR Unit on Global Surgery (Universities of Birmingham, Edinburgh and Warwick), University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK.
    Sund, Malin (Contributor)
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Andersson, Linda (Contributor)
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Gunnarsson, Ulf (Contributor)
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study2018In: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 32, no 8, p. 3450-3466Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide.

    METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days.

    RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45).

    CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments.

    TRIAL REGISTRATION: NCT02179112.

  • 774.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study.2018In: Lancet. Infectious diseases (Print), ISSN 1473-3099, E-ISSN 1474-4457, Vol. 18, no 5, p. 516-525, article id S1473-3099(18)30101-4Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world.

    METHODS: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231.

    FINDINGS: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p<0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05-2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p<0·001).

    INTERPRETATION: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication.

    FUNDING: DFID-MRC-Wellcome Trust Joint Global Health Trial Development Grant, National Institute of Health Research Global Health Research Unit Grant.

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