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  • 1.
    Berglund, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Biomolecular Aspects of Flexor Tendon Healing2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Flexor tendon injuries in zone II of the hand (i.e. between the distal volar crease and the distal interphalangeal joint) can be costly for both the afflicted individual and society because of the high cost of a long rehabilitation period, complicated by tendon ruptures or scarring with adhesion formation, causing impaired range of motion. The aim of the present thesis was to characterize more fully the deep flexor tendon, the tendon sheath and their response to injury in a rabbit model in order to find potential targets to improve the outcome of repair.

    The intrasynovial rabbit deep flexor tendon differed from the extrasynovial peroneus tendon in the expression of collagens and transforming growth factor-β1 gene expression. Differences were also found in collagen III and proteoglycans between regions of the flexor tendon subjected to either compressive or tensile load.

    After laceration and subsequent repair of the flexor tendon, a shift in collagen gene expression from type I to type III occurred. Proteoglycans were generally increased with the notable exception of decorin, a potential inhibitor of the profibrotic transforming growth factor-β1 which was markedly increased during the first two weeks after repair in tendon tissue but remained unaltered in the sheaths. Both vascular endothelial growth factor and basic fibroblast growth factor mRNA levels remained essentially unaltered, whereas insulin-like growth factor-1 increased later in the healing process, suggesting potential beneficial effects of exogenous addition, increasing tendon strength through stimulating tenocyte proliferation and collagen synthesis.

    Matrix metalloproteinase-13 mRNA levels increased and remained high in both tendon and sheath, whereas there was only a transient increase of matrix metalloproteinase-3 mRNA in tendon. We could also demonstrate a significant increase of the proportion of myofibroblasts, mast cells and neuropeptide containing nerve fibers in the healing tendon tissue, all components of the profibrotic myofibroblast-mast cell-neuropeptide pathway.

    List of papers
    1. The inflammatory response and hyaluronan synthases in the rabbit flexor tendon and tendon sheath following injury
    Open this publication in new window or tab >>The inflammatory response and hyaluronan synthases in the rabbit flexor tendon and tendon sheath following injury
    2007 (English)In: Journal of Hand Surgery: European Volume, ISSN 1753-1934, Vol. 32, no 5, p. 581-587Article in journal (Refereed) Published
    Abstract [en]

    Using a rabbit model of flexor tendon injury, mRNA levels for a subset of relevant molecules involved in inflammatory and fibrotic processes were assessed by reverse transcriptase-polymerase chain reaction 3, 6, 12 and 24 days after injury. Increased levels of COX-2, IL-1beta, MMP-13 and TIMP-1 mRNA were detected in both tendon and tendon sheath following injury, with each molecule exhibiting tissue and time-dependent changes. MMP-13 and TIMP-1 mRNA levels were markedly upregulated in both tissues, whereas COX-2 and IL-1beta predominantly increased in tendon. Both hyaluronan synthase (HAS) 2 and 3 exhibited increases in mRNA levels in tendon tissue after injury, HAS 2 being more pronounced. These findings support the concept that healing in the flexor tendon and the sheath involve different molecular events and that each tissue may require unique modifications if healing is to be enhanced and adhesions reduced.

    Keywords
    flexor tendon injury, hyaluronan synthases, interleukin-1B, cyclooxygenase-2, inducible nitric oxide synthase
    National Category
    Medical and Health Sciences
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-119913 (URN)10.1016/j.jhse.2007.05.017 (DOI)000251160000021 ()17950228 (PubMedID)
    Available from: 2010-03-03 Created: 2010-03-03 Last updated: 2011-01-14Bibliographically approved
    2. Patterns of mRNA expression for matrix molecules and growth factors in flexor tendon injury: differences in the regulation between tendon and tendon sheath
    Open this publication in new window or tab >>Patterns of mRNA expression for matrix molecules and growth factors in flexor tendon injury: differences in the regulation between tendon and tendon sheath
    2006 (English)In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 31A, no 8, p. 1279-1287Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: Injuries to tendons, particularly flexor tendons, can lead to loss of function after healing due to adhesion formation and other complications. The aim of this study was to increase our understanding of the healing process in tendons and tendon sheaths to develop methods to affect the healing process and improve the outcome of tendon repair in the future. METHODS: In a rabbit model of flexor tendon injury, tissues were harvested 3, 6, 12, and 24 days after surgery (n = 6 for each group). After RNA extraction, messenger RNA (mRNA) levels for relevant genes in tendon and tendon sheaths were measured using the reverse transcription polymerase chain reaction. Messenger RNA levels for a subset of relevant molecules at different time points after injury were compared with those of uninjured controls for tendons and tendon sheaths. RESULTS: Initially after injury, there was a shift in collagen expression with a marked increase in type III mRNA levels in both the tendon and tendon sheath, whereas those for collagen I increased only in the sheath at later time points. Aggrecan and versican mRNA levels were increased in both tissues, but temporal aspects of the changes were different. The mRNA levels for biglycan and lumican were all upregulated throughout the healing interval examined, whereas those for decorin were significantly decreased throughout in the tendon more so than the sheath. The mRNA levels for basic fibroblastic growth factor and transforming growth factor beta were elevated after injury in the tendon but not in the sheath. In contrast, mRNA levels for connective tissue growth factor were unaltered or decreased in both tissues throughout the interval assessed. CONCLUSIONS: Healing after injury to the rabbit flexor tendon and tendon sheath follow a reproducible pattern of gene expression; however, the pattern in the tendon is very different from that in the sheath. These findings indicate that interventions developed to improve healing of these tissues will have to address these differences, because they will likely affect the outcomes.

    Keywords
    bFGF, collagen, flexor tendon, proteoglycan, TGF-B1
    National Category
    Surgery
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-119911 (URN)10.1016/j.jhsa.2006.06.011 (DOI)000241647900004 ()17027787 (PubMedID)
    Available from: 2010-03-03 Created: 2010-03-03 Last updated: 2017-12-12Bibliographically approved
    3. Assessment of mRNA levels for matrix molecules and TGF-B1 in rabbit flexor and peroneus tendons reveals regional differences in steady-state expression
    Open this publication in new window or tab >>Assessment of mRNA levels for matrix molecules and TGF-B1 in rabbit flexor and peroneus tendons reveals regional differences in steady-state expression
    Show others...
    2004 (English)In: Journal of Hand Surgery - British and European Volume, ISSN 0266-7681, E-ISSN 1532-2211, Vol. 29, no 2, p. 165-169Article in journal (Refereed) Published
    Abstract [en]

    This study analysed the differences on a molecular level between two segments of the deep flexor tendon, and compared the intrasynovial flexor tendon with the tendon sheath and the extrasynovial peroneus tendon in a rabbit model. The TRIspin method of RNA extraction was combined with the reverse transcription polymerase chain reaction to assess mRNA levels in the tissue segments. Significant differences were detected for all genes studied. mRNA levels for aggrecan, biglycan and collagen III were significantly higher in the fibrocartilaginous proximal segment of the flexor tendon. Collagen I was higher in the flexor tendon than the sheath and the peroneus tendon, and TGF-beta1 was significantly lower in the peroneus tendon. This study demonstrates differences at the mRNA level between different segments of tendon, indicating that the tendon tissue may be adapted to its environment.

    Keywords
    flexor tendon, proteoglycan, collagen, tendon heterogeneity
    National Category
    Surgery
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-119914 (URN)10.1016/j.jhsb.2003.09.005 (DOI)15010165 (PubMedID)
    Available from: 2010-03-03 Created: 2010-03-03 Last updated: 2017-12-12Bibliographically approved
    4. Neuropeptide, mast cell and myofibroblast expression after rabbit deep flexor tendon repair
    Open this publication in new window or tab >>Neuropeptide, mast cell and myofibroblast expression after rabbit deep flexor tendon repair
    Show others...
    2010 (English)In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 35, no 11, p. 1842-1849Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: Increased numbers of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers have been found in a number of fibrotic processes in connective tissues. The purpose of the present study was to investigate the occurrence of factors implicated in a hypothesized profibrotic neuropeptide-mast cell-myofibroblast pathway in deep flexor tendon healing.

    METHODS: In a rabbit model of flexor tendon injury, with repair of the sharply transected deep flexor tendon using a modified Kessler and a running circumferential peripheral suture, segments of flexor tendons and sheaths were analyzed. The time points chosen-3, 6, 21, and 42 days after tendon repair-represent different stages in tendon healing. The messenger RNA levels of transforming growth factor-β1 and α-smooth muscle actin were measured with conventional reverse transcription-polymerase chain reaction, and the numbers of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers were determined with immunohistochemistry.

    RESULTS: The messenger RNA levels for transforming growth factor-β1 and the myofibroblast marker α-smooth muscle actin were significantly increased in deep flexor tendons after injury and repair, at all studied time points, but remained unchanged or even down-regulated in the sheaths. Myofibroblasts, mast cells, and neuropeptide-containing nerve fibers all increased significantly in the healing tendons, exhibiting similar patterns of change in percentages of total cell number over time, reaching levels resembling that of the tendon sheaths with 33% to 50% of the total cell population.

    CONCLUSIONS: After injury to the deep flexor tendon in a rabbit model, the proportion of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers increases significantly. These findings support the hypothesis that the profibrotic neuropeptide-mast cell-myofibroblast pathway is activated in deep flexor tendon healing.

    Keywords
    a-SMA, flexor tendon healing, mast cell, myofibroblast, neuropeptide, TGF-β1
    National Category
    Surgery
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-119917 (URN)10.1016/j.jhsa.2010.06.031 (DOI)000284031400016 ()20888142 (PubMedID)
    Available from: 2010-03-03 Created: 2010-03-03 Last updated: 2017-12-12Bibliographically approved
    5. Growth Factor and Protease Expression during Different Phases of Healing after Rabbit Deep Flexor Tendon Repair
    Open this publication in new window or tab >>Growth Factor and Protease Expression during Different Phases of Healing after Rabbit Deep Flexor Tendon Repair
    2011 (English)In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 29, no 6, p. 886-892Article in journal (Refereed) Published
    Abstract [en]

    The purpose of the study was to contribute to the mapping of molecular events during flexor tendon healing, in particular the growth factors insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), matrix metalloproteinases (MMP-3 and MMP-13) and their inhibitors (tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-3, and the protease cathepsin K. In a rabbit model of flexor tendon injury, the mRNA expression for the growth factors, MMPs and TIMPs were measured in tendon and tendon sheath tissue at several time points (3, 6, 21, and 42 days) representing different phases of the healing process. We found that MMP-13 remained increased during the study period, whereas MMP-3 returned to normal levels within the first week after injury. TIMP-3 was down-regulated in the tendon sheaths. Cathepsin K was up-regulated in tendons and sheaths after injury. NGF was present in both tendons and sheaths, but unaltered. IGF-1 exhibited a late increase in the tendons, while VEGF was down-regulated at the later time points. In conclusion, we have demonstrated the presence of NGF in flexor tendons. MMP-13 expression appears to play a more protracted role in flexor tendon healing than MMP-3. The relatively low levels of endogenous IGF-1 and VEGF mRNA following injury support their potential beneficial role as exogenous modulators to optimize tendon healing and strength without increasing adhesion formation.

    Keywords
    tendon healing, VEGF, IGF-1, NGF, MMP, TIMP
    National Category
    Surgery
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-120515 (URN)10.1002/jor.21330 (DOI)000290360300015 ()21246620 (PubMedID)
    Projects
    Biomolecular aspects of flexor tendon healing
    Available from: 2010-03-12 Created: 2010-03-12 Last updated: 2017-12-12Bibliographically approved
  • 2.
    Berglund, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Hart, David A.
    McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Canada.
    Reno, Carol
    McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Canada.
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Growth Factor and Protease Expression during Different Phases of Healing after Rabbit Deep Flexor Tendon Repair2011In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 29, no 6, p. 886-892Article in journal (Refereed)
    Abstract [en]

    The purpose of the study was to contribute to the mapping of molecular events during flexor tendon healing, in particular the growth factors insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), matrix metalloproteinases (MMP-3 and MMP-13) and their inhibitors (tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-3, and the protease cathepsin K. In a rabbit model of flexor tendon injury, the mRNA expression for the growth factors, MMPs and TIMPs were measured in tendon and tendon sheath tissue at several time points (3, 6, 21, and 42 days) representing different phases of the healing process. We found that MMP-13 remained increased during the study period, whereas MMP-3 returned to normal levels within the first week after injury. TIMP-3 was down-regulated in the tendon sheaths. Cathepsin K was up-regulated in tendons and sheaths after injury. NGF was present in both tendons and sheaths, but unaltered. IGF-1 exhibited a late increase in the tendons, while VEGF was down-regulated at the later time points. In conclusion, we have demonstrated the presence of NGF in flexor tendons. MMP-13 expression appears to play a more protracted role in flexor tendon healing than MMP-3. The relatively low levels of endogenous IGF-1 and VEGF mRNA following injury support their potential beneficial role as exogenous modulators to optimize tendon healing and strength without increasing adhesion formation.

  • 3.
    Berglund, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Hart, David A.
    McCaig Centre for Joint Injury and Arthritis Research, University of Calgary, Calgary, Canada.
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    The inflammatory response and hyaluronan synthases in the rabbit flexor tendon and tendon sheath following injury2007In: Journal of Hand Surgery: European Volume, ISSN 1753-1934, Vol. 32, no 5, p. 581-587Article in journal (Refereed)
    Abstract [en]

    Using a rabbit model of flexor tendon injury, mRNA levels for a subset of relevant molecules involved in inflammatory and fibrotic processes were assessed by reverse transcriptase-polymerase chain reaction 3, 6, 12 and 24 days after injury. Increased levels of COX-2, IL-1beta, MMP-13 and TIMP-1 mRNA were detected in both tendon and tendon sheath following injury, with each molecule exhibiting tissue and time-dependent changes. MMP-13 and TIMP-1 mRNA levels were markedly upregulated in both tissues, whereas COX-2 and IL-1beta predominantly increased in tendon. Both hyaluronan synthase (HAS) 2 and 3 exhibited increases in mRNA levels in tendon tissue after injury, HAS 2 being more pronounced. These findings support the concept that healing in the flexor tendon and the sheath involve different molecular events and that each tissue may require unique modifications if healing is to be enhanced and adhesions reduced.

  • 4.
    Berglund, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Hildebrand, Kevin A.
    McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Canada.
    Zhang, Mei
    McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Canada.
    Hart, David A.
    McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Canada.
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Neuropeptide, mast cell and myofibroblast expression after rabbit deep flexor tendon repair2010In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 35, no 11, p. 1842-1849Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Increased numbers of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers have been found in a number of fibrotic processes in connective tissues. The purpose of the present study was to investigate the occurrence of factors implicated in a hypothesized profibrotic neuropeptide-mast cell-myofibroblast pathway in deep flexor tendon healing.

    METHODS: In a rabbit model of flexor tendon injury, with repair of the sharply transected deep flexor tendon using a modified Kessler and a running circumferential peripheral suture, segments of flexor tendons and sheaths were analyzed. The time points chosen-3, 6, 21, and 42 days after tendon repair-represent different stages in tendon healing. The messenger RNA levels of transforming growth factor-β1 and α-smooth muscle actin were measured with conventional reverse transcription-polymerase chain reaction, and the numbers of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers were determined with immunohistochemistry.

    RESULTS: The messenger RNA levels for transforming growth factor-β1 and the myofibroblast marker α-smooth muscle actin were significantly increased in deep flexor tendons after injury and repair, at all studied time points, but remained unchanged or even down-regulated in the sheaths. Myofibroblasts, mast cells, and neuropeptide-containing nerve fibers all increased significantly in the healing tendons, exhibiting similar patterns of change in percentages of total cell number over time, reaching levels resembling that of the tendon sheaths with 33% to 50% of the total cell population.

    CONCLUSIONS: After injury to the deep flexor tendon in a rabbit model, the proportion of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers increases significantly. These findings support the hypothesis that the profibrotic neuropeptide-mast cell-myofibroblast pathway is activated in deep flexor tendon healing.

  • 5.
    Berglund, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Reno, Carol
    McCaig Centre for Joint Injury and Artrhitis Research, University of Calgary, Calgary, Canada.
    Hart, David A.
    McCaig Centre for Joint Injury and Arthritis Research, University of Calgary, Calgary, Canada.
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Patterns of mRNA expression for matrix molecules and growth factors in flexor tendon injury: differences in the regulation between tendon and tendon sheath2006In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 31A, no 8, p. 1279-1287Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Injuries to tendons, particularly flexor tendons, can lead to loss of function after healing due to adhesion formation and other complications. The aim of this study was to increase our understanding of the healing process in tendons and tendon sheaths to develop methods to affect the healing process and improve the outcome of tendon repair in the future. METHODS: In a rabbit model of flexor tendon injury, tissues were harvested 3, 6, 12, and 24 days after surgery (n = 6 for each group). After RNA extraction, messenger RNA (mRNA) levels for relevant genes in tendon and tendon sheaths were measured using the reverse transcription polymerase chain reaction. Messenger RNA levels for a subset of relevant molecules at different time points after injury were compared with those of uninjured controls for tendons and tendon sheaths. RESULTS: Initially after injury, there was a shift in collagen expression with a marked increase in type III mRNA levels in both the tendon and tendon sheath, whereas those for collagen I increased only in the sheath at later time points. Aggrecan and versican mRNA levels were increased in both tissues, but temporal aspects of the changes were different. The mRNA levels for biglycan and lumican were all upregulated throughout the healing interval examined, whereas those for decorin were significantly decreased throughout in the tendon more so than the sheath. The mRNA levels for basic fibroblastic growth factor and transforming growth factor beta were elevated after injury in the tendon but not in the sheath. In contrast, mRNA levels for connective tissue growth factor were unaltered or decreased in both tissues throughout the interval assessed. CONCLUSIONS: Healing after injury to the rabbit flexor tendon and tendon sheath follow a reproducible pattern of gene expression; however, the pattern in the tendon is very different from that in the sheath. These findings indicate that interventions developed to improve healing of these tissues will have to address these differences, because they will likely affect the outcomes.

  • 6.
    Berglund, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Torstensson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Reno, Carol
    McCaig Centre for Joint Injury and Arthritis Research, University of Calgary, Calgary, Canada.
    Hart, David A.
    McCaig Centre for Joint Injury and Arthritis Research, University of Calgary, Calgary, Canada.
    Assessment of mRNA levels for matrix molecules and TGF-B1 in rabbit flexor and peroneus tendons reveals regional differences in steady-state expression2004In: Journal of Hand Surgery - British and European Volume, ISSN 0266-7681, E-ISSN 1532-2211, Vol. 29, no 2, p. 165-169Article in journal (Refereed)
    Abstract [en]

    This study analysed the differences on a molecular level between two segments of the deep flexor tendon, and compared the intrasynovial flexor tendon with the tendon sheath and the extrasynovial peroneus tendon in a rabbit model. The TRIspin method of RNA extraction was combined with the reverse transcription polymerase chain reaction to assess mRNA levels in the tissue segments. Significant differences were detected for all genes studied. mRNA levels for aggrecan, biglycan and collagen III were significantly higher in the fibrocartilaginous proximal segment of the flexor tendon. Collagen I was higher in the flexor tendon than the sheath and the peroneus tendon, and TGF-beta1 was significantly lower in the peroneus tendon. This study demonstrates differences at the mRNA level between different segments of tendon, indicating that the tendon tissue may be adapted to its environment.

  • 7.
    Edsfeldt, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Intrasynovial flexor tendon injuries and repair2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Complications after surgical repair of intrasynovial flexor tendon injuries in the hand occur despite advanced suture techniques and structured postoperative rehabilitation regimens. Early controlled tendon mobilization prevents adhesion formations and improves tendon healing as well as digit range of motion. To allow early postoperative rehabilitation, the strength of the repair must withstand forces created during the rehabilitation maneuvers. Improvements in suture biomechanics have increased repair strength, but up to 18 percent of repaired tendons still rupture. The overarching aim of this thesis was to investigate how to best treat intrasynovial flexor tendon injuries with limited risk of repair rupture, decreased adhesion formations, and to estimate the effect of individual patient and injury characteristics on functional outcome.

    In two observational studies, we identified risk factors for rupture of repaired intrasynovial flexor digitorum profundus (FDP) tendons, and studied effects of these risk factors on the long-term outcome. Age was associated with increased risk of repair rupture and impaired digital mobility the first year after surgical repair. Concomitant flexor digitorum superficialis (FDS) transection was associated with increased risk of repair rupture without affecting digital mobility. Concomitant nerve transection lowered the rupture risk without affecting digital mobility.

    To better understand forces generated in the flexor tendons during rehabilitation maneuvers, we measured in vivo forces in the index finger FDP and FDS tendons during rehabilitation exercises. Highest forces were measured during isolated FDP and FDS flexion for the FDP and FDS respectively. For the FDS tendon, higher forces were observed with the wrist at 30° flexion compared to neutral position, and for the FDP tendon, forces were higher during active finger flexion compared to place and hold.

    PXL01 is a lactoferrin peptide with anti-adhesive effects previously demonstrated in animal studies and a clinical trial to improve digital mobility when administrated around repaired tendons. We studied the mechanism of action of its corresponding rabbit peptide, rabPXL01 in sodium hyaluronate (HA) in a rabbit model of flexor tendon transection and repair and used RT-qPCR to assess mRNA levels for different genes. Increased levels of PRG4 (encoding lubricin) were observed in rabPXL01 in HA treated tendons. The expression of Interleukin 1β, 6, and 8 was repressed in tendon sheaths. RabPXL01 in HA might stimulate the release of lubricin and diminish inflammation, which correspondingly reduces tendon-gliding resistance and adhesion formations during postoperative rehabilitation exercises.

    The results of this thesis suggest individually adapted treatment plans, depending on repair strength, patient and injury characteristics, as a possible way to improve outcome after flexor tendon repair.

    List of papers
    1. Risk factors for rupture of repaired flexor tendons in zone I and II
    Open this publication in new window or tab >>Risk factors for rupture of repaired flexor tendons in zone I and II
    (English)Article in journal (Other academic) Submitted
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-316557 (URN)
    Available from: 2017-03-02 Created: 2017-03-02 Last updated: 2017-03-15
    2. Prognostic factors for digital range of motion after intrasynovial flexor tendon injury and repair - Long-term follow-up on 311 patients treated with active extension-passive flexion with rubber bands
    Open this publication in new window or tab >>Prognostic factors for digital range of motion after intrasynovial flexor tendon injury and repair - Long-term follow-up on 311 patients treated with active extension-passive flexion with rubber bands
    (English)Article in journal (Other academic) Submitted
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-316558 (URN)
    Available from: 2017-03-02 Created: 2017-03-02 Last updated: 2017-03-15
    3. In vivo flexor tendon forces generated during different rehabilitation exercises
    Open this publication in new window or tab >>In vivo flexor tendon forces generated during different rehabilitation exercises
    Show others...
    2015 (English)In: Journal of Hand Surgery, European Volume, ISSN 1753-1934, E-ISSN 2043-6289, Vol. 40, no 7, p. 705-710Article in journal (Refereed) Published
    Abstract [en]

    We measured in vivo forces in the flexor digitorum profundus and the flexor digitorum superficialis tendons during commonly used rehabilitation manoeuvres after flexor tendon repair by placing a buckle force transducer on the tendons of the index finger in the carpal canal during open carpal tunnel release of 12 patients. We compared peak forces for each manoeuvre with the reported strength of a flexor tendon repair. Median flexor digitorum profundus force (24 N) during isolated flexor digitorum profundus flexion and median flexor digitorum superficialis force (13 N) during isolated flexor digitorum superficialis flexion were significantly higher than during the other manoeuvres. Significantly higher median forces were observed in the flexor digitorum superficialis with the wrist at 30° flexion (6 N) compared with the neutral wrist position (5 N). Median flexor digitorum profundus forces were significantly higher during active finger flexion (6 N) compared with place and hold (3 N). Place and hold and active finger flexion with the wrist in the neutral position or tenodesis generated the lowest forces; isolated flexion of these tendons generated higher forces along the flexor tendons.

    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-284410 (URN)10.1177/1753193415591491 (DOI)26115682 (PubMedID)
    Available from: 2016-04-18 Created: 2016-04-18 Last updated: 2017-08-22Bibliographically approved
    4. PXL01 in sodium hyaluronate results in increased PRG4 expression: a potential mechanism for anti-adhesion
    Open this publication in new window or tab >>PXL01 in sodium hyaluronate results in increased PRG4 expression: a potential mechanism for anti-adhesion
    Show others...
    2017 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, p. 28-34Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: To investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabbit lactoferrin peptide, rabPXL01 in HA, in a rabbit model of healing tendons and tendon sheaths. The mechanism of action for PXL01 in HA is interesting since a recent clinical study of the human lactoferrin peptide PXL01 in HA administered around repaired tendons in the hand showed improved digit mobility.

    MATERIALS AND METHODS: On days 1, 3, and 6 after tendon injury and surgical repair, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to assess mRNA expression levels for genes encoding the mucinous glycoprotein PRG4 (also called lubricin) and a subset of matrix proteins, cytokines, and growth factors involved in flexor tendon repair. RabPXL01 in HA was administered locally around the repaired tendons, and mRNA expression was compared with untreated repaired tendons and tendon sheaths.

    RESULTS: We observed, at all time points, increased expression of PRG4 mRNA in tendons treated with rabPXL01 in HA, but not in tendon sheaths. In addition, treatment with rabPXL01 in HA led to repression of the mRNA levels for the pro-inflammatory mediators interleukin (IL)-1β, IL-6, and IL-8 in tendon sheaths.

    CONCLUSIONS: RabPXL01 in HA increased lubricin mRNA production while diminishing mRNA levels of inflammatory mediators, which in turn reduced the gliding resistance and inhibited the adhesion formation after flexor tendon repair.

    Keywords
    Carcinoid heart disease, Cardiac imaging, Heart metastases, Neuroendocrine tumors
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-309615 (URN)10.1080/03009734.2016.1230157 (DOI)000396476600004 ()27658527 (PubMedID)
    Funder
    Swedish Foundation for Strategic Research
    Available from: 2016-12-06 Created: 2016-12-06 Last updated: 2017-11-29Bibliographically approved
  • 8.
    Edsfeldt, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Eklund, Martin
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Prognostic factors for digital range of motion after intrasynovial flexor tendon injury and repair - Long-term follow-up on 311 patients treated with active extension-passive flexion with rubber bandsArticle in journal (Other academic)
  • 9.
    Edsfeldt, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Eklund, Martin
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Risk factors for rupture of repaired flexor tendons in zone I and IIArticle in journal (Other academic)
  • 10.
    Edsfeldt, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Holm, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Mahlapuu, Margit
    Pergamum AB, Stockholm, Sweden.
    Reno, Carol
    Univ Calgary, McCaig Inst Bone & Joint Hlth, Dept Surg, Calgary, AB, Canada.
    Hart, David A
    Univ Calgary, McCaig Inst Bone & Joint Hlth, Dept Surg, Calgary, AB, Canada.
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    PXL01 in sodium hyaluronate results in increased PRG4 expression: a potential mechanism for anti-adhesion2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, p. 28-34Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabbit lactoferrin peptide, rabPXL01 in HA, in a rabbit model of healing tendons and tendon sheaths. The mechanism of action for PXL01 in HA is interesting since a recent clinical study of the human lactoferrin peptide PXL01 in HA administered around repaired tendons in the hand showed improved digit mobility.

    MATERIALS AND METHODS: On days 1, 3, and 6 after tendon injury and surgical repair, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to assess mRNA expression levels for genes encoding the mucinous glycoprotein PRG4 (also called lubricin) and a subset of matrix proteins, cytokines, and growth factors involved in flexor tendon repair. RabPXL01 in HA was administered locally around the repaired tendons, and mRNA expression was compared with untreated repaired tendons and tendon sheaths.

    RESULTS: We observed, at all time points, increased expression of PRG4 mRNA in tendons treated with rabPXL01 in HA, but not in tendon sheaths. In addition, treatment with rabPXL01 in HA led to repression of the mRNA levels for the pro-inflammatory mediators interleukin (IL)-1β, IL-6, and IL-8 in tendon sheaths.

    CONCLUSIONS: RabPXL01 in HA increased lubricin mRNA production while diminishing mRNA levels of inflammatory mediators, which in turn reduced the gliding resistance and inhibited the adhesion formation after flexor tendon repair.

  • 11.
    Edsfeldt, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Rempel, D
    Kursa, K
    Diao, E
    Lattanza, L
    In vivo flexor tendon forces generated during different rehabilitation exercises2015In: Journal of Hand Surgery, European Volume, ISSN 1753-1934, E-ISSN 2043-6289, Vol. 40, no 7, p. 705-710Article in journal (Refereed)
    Abstract [en]

    We measured in vivo forces in the flexor digitorum profundus and the flexor digitorum superficialis tendons during commonly used rehabilitation manoeuvres after flexor tendon repair by placing a buckle force transducer on the tendons of the index finger in the carpal canal during open carpal tunnel release of 12 patients. We compared peak forces for each manoeuvre with the reported strength of a flexor tendon repair. Median flexor digitorum profundus force (24 N) during isolated flexor digitorum profundus flexion and median flexor digitorum superficialis force (13 N) during isolated flexor digitorum superficialis flexion were significantly higher than during the other manoeuvres. Significantly higher median forces were observed in the flexor digitorum superficialis with the wrist at 30° flexion (6 N) compared with the neutral wrist position (5 N). Median flexor digitorum profundus forces were significantly higher during active finger flexion (6 N) compared with place and hold (3 N). Place and hold and active finger flexion with the wrist in the neutral position or tenodesis generated the lowest forces; isolated flexion of these tendons generated higher forces along the flexor tendons.

  • 12.
    Ekblom, Anna Gerber
    et al.
    Karolinska Institutet, Södersjukhuset, SE-118 83, Stockholm, Sweden.
    Dahlin, Lars B
    Department of Clinical Sciences Malmö, Section of Hand Surgery, Lund University, Jan Waldenströms gata 59, SE-205 02, Malmö, Sweden..
    Rosberg, Hans-Eric
    Department of Clinical Sciences Malmö, Section of Hand Surgery, Lund University, Jan Waldenströms gata 59, SE-205 02, Malmö, Sweden..
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Werner, Michael
    Karolinska Institutet, Södersjukhuset, SE-118 83, Stockholm, Sweden.
    Arner, Marianne
    Karolinska Institutet, Södersjukhuset, SE-118 83, Stockholm, Sweden.
    Hand Function in Adults with Radial Longitudinal Deficiency2014In: Journal of Bone and Joint Surgery. American volume, ISSN 0021-9355, E-ISSN 1535-1386, Vol. 96, no 14, p. 1178-1184Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Functional impairment in individuals with radial longitudinal deficiency can be influenced by several factors, including a short and bowed forearm, radial deviation of the wrist, a non-functional or absent thumb, limited finger motion, and impaired grip strength, but their relationship with activity and participation in adults with radial deficiency is not known.METHODS: Twenty individuals, eighteen to sixty years of age, who had Bayne type-II to V radial longitudinal deficiency, were examined in the context of the International Classification of Functioning, Disability and Health. Body function and structure were evaluated by measures of range of motion, grip strength, key pinch, sensibility, and radiographic parameters. Activity was evaluated by the Box and Block Test and the Sollerman test, and participation was evaluated by QuickDASH (the short form of the Disabilities of Arm, Shoulder and Hand outcome measure) and by the Medical Outcomes Study 12-Item Short Form Health Survey. Statistical correlations among assessments of body function and structure, activity, and participation were examined.RESULTS: The mean total active motion of the wrist (43°) and mean total active motion of the digits (377°) were less than the norms. The mean radial deviation of the wrist was 31°. The mean grip strength (4.0 kg), key pinch (1.4 kg), and scores for the Box and Block Test (55 blocks per minute) and the Sollerman test on hand function (56 points) were considerably lower than the norms. The mean scores were 18 points for QuickDASH, 51 points for Short Form-12 physical component summary, and 53 points for Short Form-12 mental component summary. Significant relationships were found between the Box and Block Test and grip strength (p = 0.012), key pinch (p < 0.001), and total active motion of digits (p < 0.001); between the Sollerman test and the total active motion of elbow (p < 0.001) and the total active motion of digits (p < 0.001); between the QuickDASH and forearm length (p < 0.001), the total active motion of elbow (p = 0.001), and the total active motion of digits (p < 0.001); between the Short Form-12 physical component summary and grip strength (p = 0.016), forearm length (p < 0.001), total active elbow motion (p < 0.001), and total active digit motion (p < 0.001); and between the Short-Form-12 mental component summary and radial deviation of the wrist (p = 0.019). No significant correlations were found between the radiographic measurement of the radial deviation of the wrist (total forearm angle) and the Box and Block Test (p = 0.244), the Sollerman test (p = 0.775), QuickDASH (p = 0.156), Short Form-12 physical component summary (p = 0.107), or Short Form-12 mental component summary (p = 0.129).CONCLUSIONS: In individuals with radial longitudinal deficiency, grip strength, key pinch, forearm length, and elbow and digital motion seem to be more important for the individual's activity and participation than the radial angulation of the wrist.LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

  • 13. Ekblom, Anna Gerber
    et al.
    Dahlin, Lars B
    Rosberg, Hans-Eric
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Werner, Michael
    Arner, Marianne
    Hand function in children with radial longitudinal deficiency2013In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 14, p. 116-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    In children with hypoplasia or aplasia of the radius (radial longitudinal deficiency) manual activity limitations may be caused by several factors; a short and bowed forearm, radial deviation of the wrist, a non-functional or absent thumb, limited range of motion in the fingers and impaired grip strength. The present study investigates the relation between these variables and activity and participation in children with radial dysplasia.

    METHODS:

    Twenty children, age 4-17 years, with radial longitudinal dysplasia Bayne type II-IV were examined with focus on the International Classification of Functioning and Health, version for Children and Youth (ICF-CY) context. Body function/structure was evaluated by measures of range of motion, grip strength, sensibility and radiographic parameters. Activity was examined by Box and Block Test and Assisting Hand Assessment (AHA). Participation was assessed by Children's Hand-use Experience Questionnaire (CHEQ). Statistical correlations between assessments of body function/structure and activity as well as participation were examined.

    RESULTS:

    The mean total active motion of wrist (49.6°) and digits (447°) were less than norms. The mean hand forearm angle was 34° radially. Ulnar length ranged from 40 to 80% of age-related norms. Grip strength (mean 2.7 kg) and Box and Block Test (mean 33.8 blocks/minute) were considerably lower than for age-related norms. The mean score for the AHA was 55.9 and for CHEQ Grasp efficiency 69.3. The AHA had significant relationship with the total range of motion of digits (p = 0.042). Self-experienced time of performance (CHEQ Time) had significant relationship with total active motion of wrist (p = 0.043). Hand forearm angle did not show any significant relationship with Box and Block Test, AHA or CHEQ.

    CONCLUSION:

    In radial longitudinal deficiency total range of motion of digits and wrist may be of more cardinal importance to the child's activity and participation than the angulation of the wrist.

  • 14.
    Holm, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    ABC om handinfektioner2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 48, p. 3056-9Article in journal (Refereed)
  • 15.
    Håkansson, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Mahlapuu, Margit
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Ekström, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Olmarker, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Effect of lactoferrin peptide (PXL01) on rabbit digit mobility after flexor tendon repair2012In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 37, no 12, p. 2519-2525Article in journal (Refereed)
    Abstract [en]

    Purpose: Restoration of digital function after flexor tendon injuries remains a clinical challenge. Complications such as adhesion formation and tendon rupture can lead to limited hand function. The aim of this study was to compare the effects of the lactoferrin-derived peptide, PXL01, formulated in sodium hyaluronate (SH), with SH alone on joint mobility as an indirect measure of postsurgical adhesion prevention and healing strength of the tendon and to elucidate the most optimal concentration of PXL01. Methods: Using a rabbit flexor tendon repair model, in which the deep flexor tendon was fully transected and repaired, PXL01 in SH or SH alone was administered between the repaired tendon and the tendon sheath before closure of the surgical wound. Three concentrations of PXL01 in SH (5, 20, or 40 mg/mL) were compared to determine the lowest effective concentration. The repaired tendons were evaluated 7 weeks after surgery by measuring the proximal interphalangeal joint mobility by full range of flexion assessment and the tendon repair strength. Results: Treatment with PXL01 formulated in SH resulted in improved mobility of the proximal interphalangeal joint with an average of 10°, corresponding to improvement of approximately 25% to 60% of the flexion of nonoperated toes at the different measuring points compared with SH alone. The difference was statistically significant in 5 out of 6 measuring points (0.5, 1, 2, 3, and 4 N; P <.05). The dose-response study indicated that the lowest effective concentration of PXL01 was 20 mg/mL. There was no difference in healing strength of the tendon between the groups as assessed by load-to-failure breaking strength. Conclusions: PXL01 in SH significantly improved the mobility compared with the carrier SH alone, without any negative effect on healing strength, and PXL01 at 20 mg/mL was the lowest effective concentration. Clinical relevance: The result provides a valuable basis for a clinical trial to assess efficacy and safety of PXL01 in clinical hand surgery.

  • 16.
    Kalliomäki, Maija
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Kieseritzky, Johanna V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Schmidt, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Hägglöf, Björn
    Karlsten, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjögren, Niclas
    Albrecht, Phil
    Gee, Lucy
    Rice, Frank
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Schmelz, Martin
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Structural and functional differences between neuropathy with and without pain?2011In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 231, no 2, p. 199-206Article in journal (Refereed)
    Abstract [en]

    We aimed to find functional and structural differences in neuropathy between patients with and without chronic pain following nerve injury. We included 30 patients requiring hand surgery after a trauma, with 21 reporting chronic pain for more than one year after the injury, while 9 did not suffer from injury-related chronic pain. We assessed mechanical sensitivity, thermal thresholds, electrically induced pain and axon reflex erythema and cutaneous nerve fiber density in skin biopsies of the injured site and its contralateral control. Epidermal fiber density of the injured site was reduced similarly in both patient groups. Thresholds for cold and heat pain and axon reflex areas were reduced in the injured site, but did not differ between the patient groups. Only warmth thresholds were better preserved in the pain patients (35.2 vs. 38.4 degrees C). Neuronal CGRP staining did not reveal any difference between pain and non-pain patients. Epidermal innervation density correlated best to warmth detection thresholds and deeper dermal innervation density to the area of the axon reflex erythema. No specific pattern of subjective, functional or structural parameters was detected that would separate the neuropathy patients into pain and non-pain patients. Specific staining of additional targets may help to improve our mechanistic understanding of pain development.

  • 17.
    Lindqvist, Aron
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Berglund, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    von Kieseritzky, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Assessment of the severity of injuries to hands by powered wood splitters2010In: Journal of Plastic Surgery and Hand Surgery, ISSN 2000-6764, Vol. 44, no 4-5, p. 237-244Article in journal (Refereed)
    Abstract [en]

    Our aim was to rate the severity of injuries to hands by powered wood splitters. The patients were identified from a computerised registry and the cause of injury was confirmed by written questionnaire and structured telephone interview. Information about the anatomy of the injuries was gathered from patients’ records and radiographs. Severity of injury was rated according to the Hand Injury Severity Scoring System (HISS system) and the Injury Severity Score (ISS). The reliability of HISS rating was tested. The mean Hand Injury Severity Score (HISS) was 63 and the mean ISS was 3.7. Twenty-five (19 %) of patients had minor, 41 (31 %) had moderate, 30 (23 %) had severe, and 35 (27 %) had major injuries when scored by the HISS system. Children’s injuries were more severe than those of adults. There was no difference in severity between injuries made by wedge and screw splitters. It is not possible to avoid serious hand injuries from powered wood splitters completely by prohibiting one of the two main types of splitter.

  • 18.
    Lindqvist, Aron
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hand injury from powered wood splitters2008In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 42, no 5, p. 246-52Article in journal (Refereed)
    Abstract [en]

    We describe the types of hand injury sustained from powered wood splitters. Information about all patients with such injuries treated at the Department of Hand Surgery, University Hospital, Uppsala, during the period 1995-2001 was collected from their records, and from written questionnaires and telephone interviews. Fourteen of the 131 patients found were below the age of 15. There was no change in the annual injury rate for inpatients. Wedge splitters caused 82% and screw splitters 18% of all injuries. The part of the hand most often injured by screw splitters was the metacarpus and by wedge splitters the index finger. Screw splitters caused palmar perforation, avulsion of the thumb, and shredding injuries. Traumatic amputation and devascularising injuries were also common. Hand injury from powered wood splitters is an important and continuing problem. Most injuries are caused by wedge splitters, injuries caused by screw splitters differ from those caused by wedge splitters. Preventive measures are needed and should include keeping children away from splitters. Further research to facilitate prevention is warranted.

  • 19.
    Lindqvist, Aron
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Hjalmarsson, Marielle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    DASH and Sollerman test scores after hand injury from powered wood splitters2011In: Journal of Hand Surgery, European Volume, ISSN 1753-1934, Vol. 36E, no 1, p. 57-61Article in journal (Refereed)
    Abstract [en]

    The purpose of the study was to describe the outcome after hand injury from powered wood splitters, and to investigate the relation between injury severity and outcome. Injury severity was rated according to the Hand Injury Severity Scoring System (HISS system) and the Injury Severity Score method. The patients were evaluated with the Disabilities of the Arm Shoulder and Hand outcome questionnaire (DASH), and 26 of the most severely injured patients were evaluated with the Sollerman test. The mean DASH score was moderately elevated at 15, indicating that many of these patients have sequelae. A statistically significant correlation between HISS and DASH scores was found, implying that initial injury severity is of importance for outcome. The mean Sollerman score in the injured hand was 66, which amounts to a significantly impaired hand function.

  • 20.
    Lindqvist, Aron
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hand injury from powered wood splitters: machine safety, patterns of use and injury events2011In: International Journal of Occupational Safety and Ergonomics, ISSN 1080-3548, E-ISSN 2376-9130, Vol. 17, no 2, p. 175-186Article in journal (Refereed)
    Abstract [en]

    Introduction: The purpose of this study was to describe factors of possible importance for the occurrence of hand injury from powered wood splitters.

    Patients: Patients were identified by a computerized patient registry. Information was obtained from hospital records, a written questionnaire and a structured telephone interview.

    Results: Very few splitters were constructed according to European Standards. Twenty-one percent of patients injured by wedge splitters thought that having more than one person at the machine was one cause of the accident. Seventy-nine percent of patients injured by screw splitters stated that glove use was one cause of the accident.

    Conclusions: The level of safety in wood splitters that cause hand injury is often poor. Having more than one person at the machine during work may contribute to wedge splitter injury. Glove use commonly contributes to screw splitter injury. Prevention should be directed towards unsafe machines and dangerous patterns of use.

  • 21.
    Muder, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Vedung, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Interosseous-lumbrical adhesions secondary to an infection: a case report2014In: Journal of Medical Case Reports, ISSN 1752-1947, E-ISSN 1752-1947, Vol. 8, p. 301-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Adhesions between the tendons to the interosseous muscles, the lumbrical muscles and occasionally the deep transverse metacarpal ligament can be symptomatic and cause chronic discomfort in the distal part of the hand. Reports about the condition are rare and the causal factors in previous publications are in principle limited to crush injuries and contusion from a direct blow to the hand. We present a case with typical clinic findings secondary to an infection after a cat bite. To the best of our knowledge symptomatic interosseus-lumbrical adhesions caused by an infection has never been described previously.

    CASE PRESENTATION: Our case report describes a 25-year-old Caucasian woman with chronic pain and swelling between her second and third metacarpal heads. Symptoms occurred especially under stress and developed secondary to an infection after a cat bite. Surgical exploration revealed localized adhesions between her second lumbrical muscle, her first palmar interosseous muscle and her deep transverse metacarpal ligament. The symptoms were completely relieved by surgical release of the adhesions, partial resection of the deep transverse metacarpal ligament and immediate postoperative physiotherapy.

    CONCLUSIONS: Physicians involved in hand surgery should be aware of the condition and look for it in patients complaining about distal intermetacarpal pain. The major causal factors for developing symptomatic interosseous-lumbrical adhesions are crush injuries or contusion to the distal part of the hand but it may also occur after an infection.

  • 22. Nilsson, Anders
    et al.
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Alnehill, Hakan
    Berggren, Magnus
    Bjornum, Sten
    Geijer, Mats
    Kopylov, Philippe
    Sollerman, Christer
    The Artelon CMC spacer compared with tendon interposition arthroplasty: A randomized, controlled, multicenter study of 109 patients with osteoarthritis followed for 1 year2010In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, no 2, p. 239-246Article in journal (Refereed)
    Abstract [en]

    Background and purpose The Artelon CMC spacer is designed for surgical treatment of osteoarthritis (OA) in the carpometacarpal joint of the thumb (CMC-I). Good results using this degradable device were previously presented in a pilot study. We now present results from a larger randomized, controlled, multicenter study. Patients and methods 109 patients (94 females) with a mean age of 60 (42-83) years, suffering from painful CMC OA, were included in the study at 7 centers in Sweden. The patients were randomized to Artelon CMC spacer (test, n = 72) or tendon arthroplasty (control, n = 37) at a ratio of 2:1. Perceived pain was recorded on a visual analog scale (VAS) before treatment and after 3, 6, and 12 months, when measuring maximal tripod pinch strength (primary outcome measure). In addition, range of motion, radiographic findings, and functional testing were recorded pre- and postoperatively. Results Swelling and pain were more common in the test group and 6 implants were removed because of such symptoms. 5 of these patients did not receive antibiotics preoperatively according to the study protocol. In a per-protocol analysis, i.e. patients without signs of concomitant OA in the scaphoid-trapezium-trapezoid (STT) joint and those in the test group who received antibiotics, the mean difference in tripod pinch strength increase, adjusted for baseline, was 1.4 kg in favor of the test group (not statistically significant). Statistically significant pain relief was achieved in both groups, with perceived pain gradually decreasing during the follow-up period. In the intention-to-treat analysis but not in the per-protocol analysis, significantly better pain relief (VAS) was obtained in the control group. Patient-perceived disability evaluated by the DASH questionnaire improved in both groups. Interpretation The Artelon CMC spacer did not show superior results compared to tendon interposition arthroplasty. Proper use of preoperative antibiotics and a thorough patient selection appear to be important for the results.

  • 23. Olmarker, Kjell
    et al.
    Ekstrom, Lars
    Hakansson, Joakim
    Nilsson, Elin
    Wiig, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Mahlapuu, Margit
    Model for assessment of mobility of toes and healing of tendons in rabbits2010In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 44, no 6, p. 266-271Article in journal (Refereed)
    Abstract [en]

    Repair of a transected flexor tendon will, despite careful technique and early rehabilitation, usually result in a restricted range of movement. This is mainly because adhesions form between the tendon and the surrounding structures. Our aim was to establish an experimental model in rabbits for future studies on new techniques to reduce the formation of adhesions after zone II repair of flexor tendons. In rabbits' hind paws the metatarsal bones II, IV, and V were removed and the flexor tendon was freed to the metatarsophalangeal (MTP) joint. The digits were secured in a specifically-designed biomechanical testing device comprising a servo-hydraulic actuator that was designed to apply controlled force or displacement. The tests were videotaped with a digital force-monitor behind the tested digit. Paper printouts from the recordings were obtained for 0, 0.5, 1, 2, 3, 4, and 5 Newton (N) and metatarsophalangeal, proximal interphalangeal, and distal interphalangeal, angles and distances between metatarsophalangeal joints and claws were measured. The tensile strength of the tendon was evaluated by a load-to-failure test. The continuous data obtained from the experiments were used to calculate functional stiffness at the selected forces. The model allows for unique continuous recordings of mobility of toes, thereby indirectly quantifying the presence of adhesions and the assessment of tensile strength. The data are reproducible, and there is little variation between the digits tested. The model is primarily intended to compare data among treated and non-treated digits of methods to limit the formation of adhesions after tendons have been repaired.

  • 24. Peimer, C A
    et al.
    Wilbrand, Stephan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Gerber, R A
    Chapman, D
    Szczypa, P P
    Safety and tolerability of collagenase Clostridium histolyticum and fasciectomy for Dupuytren's contracture2015In: Journal of Hand Surgery, European Volume, ISSN 1753-1934, E-ISSN 2043-6289, Vol. 40, no 2, p. 141-149Article in journal (Refereed)
    Abstract [en]

    Safety was evaluated for collagenase Clostridium histolyticum (CCH) based on 11 clinical trials (N = 1082) and compared with fasciectomy data in a structured literature review of 48 European studies (N = 7727) for treatment of Dupuytren's contracture. Incidence of adverse events was numerically lower with CCH vs. equivalent complications from fasciectomy (median [range] incidence), including nerve injury (0% vs. 3.8% [0%-50+%]), neurapraxia (4.4% vs. 9.4% [0%-51.3%]), complex regional pain syndrome (0.1% vs. 4.5% [1.3%-18.5%]) and arterial injury (0% vs. 5.5% [0.8%-16.5%]). Tendon injury (0.3% vs. 0.1% [0%-0.2%]), skin injury (16.2% vs. 2.8% [0%-25.9%]) and haematoma (77.7% vs. 2.0% [0%-25%]) occurred at a numerically higher incidence with CCH than surgery. Adverse events in CCH trials not reported after fasciectomy included peripheral oedema; extremity pain; injection site pain, haemorrhage and swelling; tenderness; pruritus and lymphadenopathy. CCH-related adverse events were reported as predominantly injection-related and transient. These results may support clinical decision-making for treatment of Dupuytren's contracture.

  • 25. Schliemann, Benedikt
    et al.
    Muder, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Gessmann, Jan
    Schildhauer, Thomas A
    Seybold, Dominik
    Locked posterior shoulder dislocation: treatment options and clinical outcomes.2011In: Archives of Orthopaedic and Trauma Surgery, ISSN 0936-8051, E-ISSN 1434-3916, Vol. 131, no 8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Posterior dislocation of the shoulder is a rare injury and often misdiagnosed during the initial presentation to a physician. Misdiagnosis is due to a lack of clear clinical signs compared to anterior dislocation and inappropriate radiographs. In contrast to anterior dislocations, the humeral head defect accounts for recurrent instability. Depending on the size of the defect and the duration of dislocation, different treatment options include elevation of the defect, bone grafting, McLaughlin procedure, rotation osteotomy or arthroplasty.

    METHODS: We reviewed 35 patients who presented to our institution with a locked posterior dislocation of the shoulder between January 1999 and August 2009. In 6 patients, the shoulder remained stable after closed reduction, so the treatment was conservative; 29 patients underwent surgery.

    RESULTS: The mean follow-up was 55 months (range 11-132 months). The interval between trauma and the diagnosis of posterior shoulder dislocation was 66 days (min. 0, max. 365). Patients treated conservatively achieved a Constant Score of 85 points; patients who underwent operative treatment had a slightly worse outcome with an average Constant Score of 79 points. There was a high correlation between the time to the correct diagnosis and the outcome.

    CONCLUSION: Although locked posterior shoulder dislocation is uncommon and often initially misdiagnosed, satisfying results can be achieved by different surgical treatment options. Early diagnosis by detailed clinical examination and sufficient radiographic evaluation with true anterior-posterior and axillary views is essential to improve clinical results. Levl of evidence: IV.

  • 26.
    Vedung, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Parsonage-Turner syndrome and a localised swelling around the extensor tendons of the hand: a clinical sign indicating increased risk of rupture of the tendon2012In: Journal of Plastic Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 46, no 5, p. 371-373Article in journal (Refereed)
    Abstract [en]

    Two patients presented with intense pain in the shoulder followed by weakness and paralysis of muscles in the shoulder and arm, together with a peculiar swelling on the hand. The swelling seems to predispose to rupture of the extensor tendon. If this tumour is a regular finding in Parsonage-Turner syndrome, it may also help in making a definitive diagnosis.

  • 27.
    Vedung, Torbjörn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Vinnars, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Ectopic bone formation after medial femoral condyle graft to scaphoid nonunion2014In: Journal of wrist surgery, ISSN 2163-3916, Vol. 3, no 1, p. 46-9Article in journal (Refereed)
    Abstract [en]

    Free vascularized bone graft from the medial femoral condyle has been described as a superior method for treatment of recalcitrant scaphoid nonunion with proximal pole avascularity and humpback deformity. Few complications and high union rates have been reported. In a series of three patients we describe an undesired volar ossification as a potential complication of the method. The risk of developing the ectopic bone formation can be minimized if the surgeon is aware of the strong osteogenic capacity of the periosteum. Meticulous dissection of the vascular bundle to the graft is mandatory to avoid the complication. Caution is warranted so as not to leave a periosteal sleeve under the vessels at the margin of the graft.

  • 28.
    Vedung, Torbjörn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Vinnars, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Resurfacing the distal radioulnar joint with rib perichondrium: a novel method2014In: Journal of wrist surgery, ISSN 2163-3916, Vol. 3, no 3, p. 206-210Article in journal (Refereed)
    Abstract [en]

    Background 

    Osteoarthritis in the distal radioulnar joint (DRUJ) is a challenging condition with few really reliable surgical options, particularly in young individuals. Traditional methods as hemiresection, the Darrach procedure, and the Sauvé-Kapandji procedure have less favorable results in the nonrheumatoid patient. The results after implant arthroplasty have improved, but long-term results are yet to be presented before implant arthroplasty can be recommended to young individuals with osteoarthritis in the DRUJ. An alternative method to treat osteoarthritic joints is surface replacement with free costal perichondrium. The technique has been used since the 1970s for other joints.

    Case Description

    We adapted the method and used it in two female patients (37 and 38 years old) with nontraumatic osteoarthritis in the DRUJ. Both patients had severe pain and were unable to work. The eroded joint surfaces were resected down to bleeding subchondral cortex. Perichondrium from the seventh rib was osteo-sutured and glued to the ulnar head and the sigmoid notch.

    Results

    The maximum follow-up-time in this retrospective review is 25 months. Our short-term results are encouraging in terms of pain relief, motion, grip strength, and return to work. The first patient had an excellent result and was completely normalized. The second patient has improved significantly and experiences only slight pain on heavy lifting and rotational load.

    Clinical Relevance

    Free costal perichondrium may be a useful alternative for treating osteoarthritis in the DRUJ, especially in young individuals. The option for a later implant arthroplasty is preserved because most of the anatomy of the joint and all the soft tissue stabilizers are intact. Level of Evidence Therapeutic IV, Case series.

  • 29.
    Vinnars, Bertil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    af Ekenstam, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Comparison of direct and indirect costs of internal fixation and cast treatment in acute scaphoid fractures: A randomized trial involving 52 patients2007In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 78, no 5, p. 672-679Article in journal (Refereed)
    Abstract [en]

    Background The most cost-effective treatment of scaphoid fractures has not yet been determined. Methods In a prospective trial, 52 employed or selfemployed patients with scaphoid fractures were randomized to closed (cast) or surgical treatment. Results There were 3 complications in the surgical group and 1 in the cast group. Median time off work was numerically but not statistically significantly greater after cast than after surgery (74/39 days). Manual workers (manuals) had a longer time away from work than non-manual employees/individuals who were selfemployed (non-manuals; median 84 days and 16 days, respectively; p < 0.001) and they had a longer time off work after cast than after surgery (median 100 days and 61 days; p = 0.03). Hospital costs were lower after cast than after surgery (p < 0.001). Work disability costs were numerically but not statistically significantly higher after cast than after surgery, and similarly, the total costs were lower after cast than after surgery. Work disability costs and total costs were higher in manuals than in non-manuals (p < 0.001). Non-manuals had lower total costs after cast than after surgery (p = 0.05). Interpretation There was a longer period of absence from work after cast than after surgery in manuals, but not in non-manuals. In non-manuals, total costs were lower after cast than after surgery. Socioeconomic classification had a greater influence on cost than mode of treatment.

  • 30.
    Vinnars, Bertil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Pietreanu, Mihai
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Bodestedt, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    af Ekenstam, Fredrik
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Nonoperative compared with operative treatment of acute scaphoid fractures: A randomized clinical trial2008In: Journal of Bone and Joint Surgery. American volume, ISSN 0021-9355, E-ISSN 1535-1386, Vol. 90, no 6, p. 1176-1185Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Traditionally, acute nondisplaced scaphoid fractures have been treated nonoperatively in a cast, and the expected union rate approaches 90%. Internal fixation of nondisplaced scaphoid fractures has increased in popularity, and a union rate of 100% has been reported. The growing trend is to recommend internal fixation for the majority of acute scaphoid fractures. The true long-term benefits of this more complicated treatment modality have not yet been determined in randomized controlled trials. The purpose of this study was to compare the long-term results of operative fixation of acute scaphoid fractures with those of nonoperative treatment.

    METHODS:

    During the period between 1992 and 1997, eighty-three patients with an acute nondisplaced or minimally displaced scaphoid fracture were randomly allocated to, and received, either nonoperative treatment with a cast or internal fixation with a Herbert screw. At a median of ten years after the injury, seventy-five (93%) of the eighty-one patients who were still alive were assessed clinically and radiographically.

    RESULTS:

    All fractures united. A significant increase in the prevalence of osteoarthritis in the scaphotrapezial joint was found in the operatively treated group. No differences in subjective symptoms, as measured with limb-specific outcome scores, were found between the two groups. The range of motion and grip strength were greater, but not significantly greater, in the nonoperatively treated group.

    CONCLUSIONS:

    This study did not demonstrate a true long-term benefit of internal fixation, compared with nonoperative treatment, for acute nondisplaced or minimally displaced scaphoid fractures. The long-term risks of surgery should be considered when recommending operative treatment.

  • 31.
    von Kieseritzky, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Widenfalk, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Treatment of a large aneurysmal bone cyst in a 15-year-old boy using a corticospongial bone graft and a 12-year follow-up after operation2012In: Journal of Plastic Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 46, no 2, p. 132-136Article in journal (Refereed)
    Abstract [en]

    We report the case of a 15-year-old boy with a large aneurysmal bone cyst in the third metacarpal, which was operated on radically with excision of the bone and grafting from the distal radius. At 12-year follow-up the patient had good cosmetic results and a perfectly functioning hand.

  • 32.
    Widenfalk, Bertil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Wilbrand, Stephan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Vinnars, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Multiple brown tumours of the upper extremity in a patient with secondary hyperparathyroidism as a result of chronic renal failure2012In: Journal of plastic surgery and hand surgery, ISSN 2000-656X, Vol. 46, no 1, p. 52-56Article in journal (Refereed)
    Abstract [en]

    A man with chronic renal failure was referred to the hand clinic because of massive osteolytic tumours in his right arm. Secondary hyperparathyroidism and brown tumours were suggested, and he was treated by subtotal parathyroidectomy. Rapid reduction of the vast tumours was noted postoperatively.

  • 33.
    Wiig, M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Olmarker, K.
    Hakansson, J.
    Ekstrom, L.
    Nilsson, E.
    Mahlapuu, M.
    A lactoferrin-derived peptide (PXL01) for the reduction of adhesion formation in flexor tendon surgery: an experimental study in rabbits2011In: Journal of Hand Surgery (European Volume), ISSN 1753-1934, Vol. 36E, no 8, p. 656-662Article in journal (Refereed)
    Abstract [en]

    Injuries to flexor tendons can lead to loss of finger function after healing due to adhesion formation. The aim of this study was to assess the efficacy and safety of the new peptide, PXL01, in the prevention of peritendinous adhesions. The effect of a single intraoperative administration of PXL01 in sodium hyaluronate on mobility of the affected digit after surgery was assessed in a rabbit model by measuring total active motion, metatarsophalangeal-claw distance and resistance to bending the digits. Load-to-failure testing was done in the same specimens to assess tendon healing. The results demonstrated that a single application of PXL01 in sodium hyaluronate significantly improved mobility of the treated digits compared with the digits in which the same surgery was carried out but no treatment was provided. No negative effects on tendon healing were observed in connection with the treatment.

  • 34.
    Wiig, Monica E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Dahlin, Lars B.
    Friden, Jan
    Hagberg, Lars
    Larsen, Soren E.
    Wiklund, Kerstin
    Mahlapuu, Margit
    PXL01 in Sodium Hyaluronate for Improvement of Hand Recovery after Flexor Tendon Repair Surgery: Randomized Controlled Trial2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 10, p. e110735-Article in journal (Refereed)
    Abstract [en]

    Background: Postoperative adhesions constitute a substantial clinical problem in hand surgery. Fexor tendon injury and repair result in adhesion formation around the tendon, which restricts the gliding function of the tendon, leading to decreased digit mobility and impaired hand recovery. This study evaluated the efficacy and safety of the peptide PXL01 in preventing adhesions, and correspondingly improving hand function, in flexor tendon repair surgery. Methods: This prospective, randomised, double-blind trial included 138 patients admitted for flexor tendon repair surgery. PXL01 in carrier sodium hyaluronate or placebo was administered around the repaired tendon. Efficacy was assessed by total active motion of the injured finger, tip-to-crease distance, sensory function, tenolysis rate and grip strength, and safety parameters were followed, for 12 months post-surgery. Results: The most pronounced difference between the treatment groups was observed at 6 months post-surgery. At this timepoint, the total active motion of the distal finger joint was improved in the PXL01 group (60 vs. 41 degrees for PXL01 vs. placebo group, p = 0.016 in PPAS). The proportion of patients with excellent/good digit mobility was higher in the PXL01 group (61% vs. 38%, p = 0.0499 in PPAS). Consistently, the PXL01 group presented improved tip-to-crease distance (5.0 vs. 15.5 mm for PXL01 vs. placebo group, p = 0.048 in PPAS). Sensory evaluation showed that more patients in the PXL01 group felt the thinnest monofilaments (FAS: 74% vs. 35%, p = 0.021; PPAS: 76% vs. 35%, p = 0.016). At 12 months post-surgery, more patients in the placebo group were considered to benefit from tenolysis (30% vs. 12%, p = 0.086 in PPAS). The treatment was safe, well tolerated, and did not increase the rate of tendon rupture. Conclusions: Treatment with PXL01 in sodium hyaluronate improves hand recovery after flexor tendon repair surgery. Further clinical trials are warranted to determine the most efficient dose and health economic benefits.

  • 35.
    Witthaut, Jörg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Bushmakin, Andrew G.
    Gerber, Robert A.
    Cappelleri, Joseph C.
    Le Graverand-Gastineau, Marie-Pierre Hellio
    Determining Clinically Important Changes in Range of Motion in Patients with Dupuytren's Contracture: Secondary Analysis of the Randomized, Double-Blind, Placebo-Controlled CORD I Study2011In: Clinical drug investigation, ISSN 1173-2563, E-ISSN 1179-1918, Vol. 31, no 11, p. 791-798Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVE:

    Injectable collagenase Clostridium histolyticum is efficacious in correcting Dupuytren's contracture as assessed by changes in the angle of contracture and range of motion (ROM). However, clinically important changes in ROM have not been evaluated in depth. The objective of this secondary analysis of the CORD I trial was to identify severity levels using baseline ROM, estimate a clinically important difference (CID) for ROM, and link the results to collagenase treatment and patient satisfaction.

    METHODS:

    In the CORD I trial, patients with Dupuytren's disease and joint contractures ≥20° were randomized to receive a maximum of three collagenase 0.58 mg or placebo injections into the cord of the affected hand at 30-day intervals. The primary endpoint was reduction in contracture to ≤5° 30 days after the last injection (day 30). The secondary endpoints, which are reported in this analysis, were ROM, physician- and patient-rated severity ('normal', 'mild', 'moderate', 'severe') and improvement, and treatment satisfaction. Linear regression was used to model data for severity classification and CID estimation for ROM based on physician and patient ratings.

    RESULTS:

    At baseline, mean ROM was 43.9° in the collagenase-treated joints (n = 197) and 45.3° in the placebo-treated joints (n = 102). On day 30, mean ROM was 80.7° in the collagenase-treated joints and 49.5° in the placebo-treated joints. The mean increase in ROM was 36.7° in the collagenase-treated joints (p < 0.001) and 4.0° in the placebo-treated joints (not significant). The estimated CID for ROM was 13.5° (95% CI 11.9, 15.1), reflecting a one-category change in severity. The mean increase in ROM exceeded the CID in the collagenase-treated joints but not in the placebo-treated joints; the difference between collagenase treatment and placebo in the mean increase in ROM also exceeded the CID, implying that the improvement with collagenase was clinically relevant. The severity classification for ROM was: ≥67.0° ('normal'), ≥54.3 and <67.0° ('mild'), ≥41.6 and <54.3° ('moderate'), and <41.6° ('severe'). More collagenase- than placebo-treated patients achieved 'normal' (81% vs 25%; p < 0.0001) status, and more collagenase- than placebo-treated patients reported being 'very/quite satisfied' (87% vs 32%; p < 0.001).

    CONCLUSION:

    Injectable collagenase significantly improves ROM and treatment satisfaction versus placebo. ROM improvements are clinically relevant as well as statistically significant. These data support the potential need to include ROM and physician- and patient-rated severity and satisfaction as standard assessments for Dupuytren's contracture treatment outcomes.

    TRIAL REGISTRATION:

    ClinicalTrials.gov Identifier: NCT00528606; other study identification number: AUX-CC-857 (Auxilium Pharmaceuticals, Inc.).

  • 36.
    Witthaut, Jörg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Jones, Graeme
    Skrepnik, Nebojsa
    Kushner, Harvey
    Houston, Anthony
    Lindau, Tommy R.
    Efficacy and Safety of Collagenase Clostridium Histolyticum Injection for Dupuytren Contracture: Short-Term Results From 2 Open-Label Studies2013In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 38A, no 1, p. 2-11Article in journal (Refereed)
    Abstract [en]

    Purpose The JOINT I (United States) and JOINT II (Australia and Europe) studies evaluated the efficacy and safety of collagenase clostridium histolyticum (CCH) injection for the treatment of Dupuytren contracture. Methods Both studies used identical open-label protocols. Patients with fixed-flexion contractures of metacarpophalangeal (MCP) (20 degrees to 100 degrees) or proximal inteiphalangeal (PIP) joints (20 degrees to 80 degrees) could receive up to three 0.58-mg CCH injections per cord (up to 5 total injections per patient). We perfonned standardized finger extension procedures to disrupt injected cords the next day, with follow-up 1, 2, 6, and 9 months thereafter. The primary end point (clinical success) was reduction in contracture to within 0 degrees to 5 degrees of full extension 30 days after the last injection. Clinical improvement was defined as 50% or more reduction from baseline contracture. Results Dupuytren cords affecting 879 joints (531 MCP and 348 PIP) in 587 patients were administered CCH injections at 14 U.S. and 20 Australian/European sites, with similar outcomes in both studies. Clinical success was achieved in 497 (57%) of treated joints using 1.2 +/- 0.5 (mean +/- SD) CCH injections per cord. More MCP than PIP joints achieved clinical success (70% and 37%, respectively) or clinical improvement (89% and 58%, respectively). Less severely contracted joints responded better than those more severely contracted. Mean change in contracture was 55 degrees for MCP joints and 25 degrees for PIP joints. With average contracture reductions of 73% and improvements in range of motion by 30 degrees, most patients (92%) were "very satisfied" (71%) or "quite satisfied" (21%) with treatment. Physicians rated change from baseline as "very much improved" (47%) or "much improved" (35%). The CCH injections were well tolerated, causing no tendon ruptures or systemic reactions. Conclusions Collagenase clostridium histolyticum was an effective, minimally invasive option for the treatment of Dupuytren contracture of a broad range of severities. Most treated joints (625 of 879) required a single injection. Treatment earlier in the course of disease provided improved outcomes.

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