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  • 1. Abul-Kasim, Kasim
    et al.
    Backman, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Björkman, Anders
    Dahlin, Lars B
    Advanced radiological work-up as an adjunct to decision in early reconstructive surgery in brachial plexus injuries2010Ingår i: Journal of Brachial Plexus and Peripheral Nerve Injury, E-ISSN 1749-7221, Vol. 5, s. 14-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    As neurophysiologic tests may not reveal the extent of brachial plexus injury at the early stage, the role of early radiological work-up has become increasingly important. The aim of the study was to evaluate the concordance between the radiological and clinical findings with the intraoperative findings in adult patients with brachial plexus injuries.

    Methods

    Seven consecutive male patients (median age 33; range 15-61) with brachial plexus injuries, caused by motor cycle accidents in 5/7 patients, who underwent extensive radiological work-up with magnetic resonance imaging (MRI), computed tomography myelography (CT-M) or both were included in this retrospective study. A total of 34 spinal nerve roots were evaluated by neuroradiologists at two different occasions. The degree of agreement between the radiological findings of every individual nerve root and the intraoperative findings was estimated by calculation of kappa coefficient (К-value). Using the operative findings as a gold standard, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the clinical findings and the radiological findings were estimated.

    Results

    The diagnostic accuracy of radiological findings was 88% compared with 65% for the clinical findings. The concordance between the radiological findings and the intraoperative findings was substantial (К = 0.76) compared with only fair (К = 0.34) for the clinical findings. There were two false positive and two false negative radiological findings (sensitivity and PPV of 0.90; specificity and NPV of 0.87).

    Conclusions

    The advanced optimized radiological work-up used showed high reliability and substantial agreement with the intraoperative findings in adult patients with brachial plexus injury.

  • 2.
    Alakpa, Enateri V.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Bahrd, Anton
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Wiklund, Krister
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Andersson, Magnus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Novikov, Lev N.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Ljungberg, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Kelk, Peyman
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Bioprinted schwann and mesenchymal stem cell co-cultures for enhanced spatial control of neurite outgrowth2023Ingår i: Gels, E-ISSN 2310-2861, Vol. 9, nr 3, artikel-id 172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bioprinting nerve conduits supplemented with glial or stem cells is a promising approach to promote axonal regeneration in the injured nervous system. In this study, we examined the effects of different compositions of bioprinted fibrin hydrogels supplemented with Schwann cells and mesenchymal stem cells (MSCs) on cell viability, production of neurotrophic factors, and neurite outgrowth from adult sensory neurons. To reduce cell damage during bioprinting, we analyzed and optimized the shear stress magnitude and exposure time. The results demonstrated that fibrin hydrogel made from 9 mg/mL of fibrinogen and 50IE/mL of thrombin maintained the gel’s highest stability and cell viability. Gene transcription levels for neurotrophic factors were significantly higher in cultures containing Schwann cells. However, the amount of the secreted neurotrophic factors was similar in all co-cultures with the different ratios of Schwann cells and MSCs. By testing various co-culture combinations, we found that the number of Schwann cells can feasibly be reduced by half and still stimulate guided neurite outgrowth in a 3D-printed fibrin matrix. This study demonstrates that bioprinting can be used to develop nerve conduits with optimized cell compositions to guide axonal regeneration.

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  • 3.
    Andersson, Gerd
    et al.
    Habiliteringscentrum, Region Västerbotten.
    Renström, Barbro
    Habiliteringscentrum, Region Västerbotten.
    Blaszczyk, Izabela
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Domellöf, Erik
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Habiliteringscentrum, Region Västerbotten.
    Upper-extremity Spasticity-reducing Treatment in Adjunct to Movement Training and Orthoses in Children with Cerebral Palsy at Gross Motor Function- and Manual Ability Classification System Levels IV-V: A Descriptive Study2020Ingår i: Developmental Neurorehabilitation, ISSN 1751-8423, E-ISSN 1751-8431, Vol. 23, nr 6, s. 349-358Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Covering a 20-year period of work with children with severe cerebral palsy (CP) within a Swedish habilitation service, changes in passive wrist extension with fingers extended (PWE-FE) and current hand function are described and compared between children receiving systematic upper-extremity treatment with botulinum neurotoxin type A and intervention programs from before 7 years of age (Group 1, n = 7), those whom for various reasons did not undergo this treatment (Group 2, n = 10), and those not having the option to receive treatment until later during childhood/adolescence (Group 3, n = 8). Group 3 showed more critical and less normal PWE-FE values for both wrists, and poorer hand function scores, particularly compared with Group 1. Findings cautiously suggest that repeated upper-extremity spasticity-reducing treatment and movement training/orthoses from an early age may help prevent critical loss of passive range of motion of the wrist joint flexion/extension and promote hand function development in children with severe CP.

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  • 4.
    Andersson, Gustav
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Backman, Ludvig J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Christensen, Jens
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Nerve distributions in insertional Achilles tendinopathy - a comparison of bone, bursae and tendon2017Ingår i: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 32, nr 3, s. 263-270Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aim. In a condition of pain in the Achilles tendon insertion there are multiple structures involved, such as the Achilles tendon itself, the retrocalcaneal bursa and a bony protrusion at the calcaneal tuberosity called Haglund's deformity. The innervation patterns of these structures are scarcely described, and the subcutaneous calcaneal bursa is traditionally not considered to be involved in the pathology. This study aimed at describing the innervation patterns of the four structures described above to provide a better understanding of possible origins of pain at the Achilles tendon insertion.

    Methods. Biopsies were taken from 10 patients with insertional Achilles tendinopathy, which had pathological changes in the subcutaneous and retrocalcaneal bursae, a Haglund deformity and Achilles tendon tendinopathy as verified by ultrasound. The biopsies were stained using immunohistochemistry in order to delineate the innervation patterns in the structures involved in insertional Achilles tendinopathy.

    Results. Immunohistochemical examinations found that the subcutaneous bursa scored the highest using a semi-quantitative evaluation of the degree of innervation when compared to the retrocalcaneal bursa, the Achilles tendon, and the calcaneal bone.

    Conclusions. These findings suggest that the subcutaneous bursa, which is traditionally not included in surgical treatment, may be a clinically important factor in insertional Achilles tendinopathy.

  • 5.
    Andersson, Gustav
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Scott, Alexander
    University of British Columbia, Vancouver, Vancouver Coastal Health and Research Institute.
    Gaida, James Edmund
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Stjernfeldt, Johanna Elgestad
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Lorentzon, Ronny
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Backman, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Tenocyte hypercellularity and vascular proliferation in a rabbit model of tendinopathy: contralateral effects suggest the involvement of central neuronal mechanisms2011Ingår i: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 45, nr 5, s. 399-406Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To determine whether there are objective findings of tendinosis in a rabbit tendinopathy model on exercised and contralateral (non-exercised) Achilles tendons. Design Four groups of six New Zealand white rabbits per group were used. The animals of one (control) group were not subjected to exercise/stimulation. Interventions Animals were subjected to a protocol of electrical stimulation and passive flexion-extension of the right triceps surae muscle every second day for 1, 3 or 6 weeks. Main Outcome Measures Tenocyte number and vascular density were calculated. Morphological evaluations were also performed as well as in-situ hybridisation for vascular endothelial growth factor (VEGF) messenger RNA. Results There was a significant increase in the tenocyte number after 3 and 6 weeks of exercise, but not after 1 week, in comparison with the control group. This was seen in the Achilles tendons of both legs in experimental animals, including the unexercised limb. The pattern of vascularity showed an increase in the number of tendon blood vessels in rabbits that had exercised for 3 weeks or more, compared with those who had exercised for 1 week or not at all. VEGF-mRNA was detected in the investigated tissue, with the reactions being more clearly detected in the tendon tissue with tendinosis-like changes (6-week rabbits) than in the normal tendon tissue (control rabbits). Conclusions There were bilateral tendinosis-like changes in the Achilles tendons of rabbits in the current model after 3 weeks of training, suggesting that central neuronal mechanisms may be involved and that the contralateral side is not appropriate as a control.

  • 6.
    Andersson, Gustav
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå Centre for Comparative Biology (UCCB).
    Sultan, Fahad
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Novikov, Lev N.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    In vivo Diffusion Tensor Imaging, Diffusion Kurtosis Imaging, and Tractography of a Sciatic Nerve Injury Model in Rat at 9.4T2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 12911Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Peripheral nerve injuries result in severe loss of sensory and motor functions in the afflicted limb. There is a lack of standardised models to non-invasively study degeneration, regeneration, and normalisation of neuronal microstructure in peripheral nerves. This study aimed to develop a non-invasive evaluation of peripheral nerve injuries, using diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and tractography on a rat model of sciatic nerve injury. 10 female Sprague Dawley rats were exposed to sciatic nerve neurotmesis and studied using a 9.4 T magnet, by performing DTI and DKI of the sciatic nerve before and 4 weeks after injury. The distal nerve stump showed a decrease in fractional anisotropy (FA), mean kurtosis (MK), axonal water fraction (AWF), and radial and axonal kurtosis (RK, AK) after injury. The proximal stump showed a significant decrease in axial diffusivity (AD) and increase of MK and AK as compared with the uninjured nerve. Both mean diffusivity (MD) and radial diffusivity (RD) increased in the distal stump after injury. Tractography visualised the sciatic nerve and the site of injury, as well as local variations of the diffusion parameters following injury. In summary, the described method detects changes both proximal and distal to the nerve injury.

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  • 7.
    Andersson, Magnus N.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Svensson, Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Björkgren, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wiberg, Rebecca
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Prophylactic mastectomy – Correlation between skin flap thickness and residual glandular tissue evaluated postoperatively by imaging2022Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1878-0539, Vol. 75, nr 6, s. 1813-1819Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Women with an increased hereditary risk of breast cancer can undergo risk-reducing prophylactic mastectomy. However, there is a balance between how much subcutaneous tissue should be resected to achieve maximal reduction of glandular tissue, while leaving viable skin flaps.

    Methods: Forty-five women previously operated with prophylactic mastectomy underwent magnetic resonance tomography (MRT) and ultrasound (US) to investigate the correlation between skin flap thickness and residual glandular tissue. Residual glandular tissue was documented as being present or not present, but not quantified, as the amount of residual glandular tissue in many cases was considered too small to make reliable volume quantifications with available tools. Since a mastectomy skin flap thickness of 5 mm is discussed as an oncologically safe thickness in the literature, this was used as a cut-off.

    Results: Following prophylactic mastectomy, residual glandular tissue was detected in 39.3% of all breasts and 27.9% of all the breast quadrants examined by MRT, and 44.1% of all breasts and 21.7% of all the breast quadrants examined by US. Residual glandular tissue was detected in 6.9% of the quadrants in skin flaps ≤ 5 mm and in 37.5% of the quadrants in skin flaps > 5 mm (OR 3.07; CI = 1.41–6.67; p = 0.005). Furthermore, residual glandular tissue increased significantly already when the skin flap thickness exceeded 7 mm.

    Conclusions: This study highlights that complete removal of glandular breast tissue during a mastectomy is difficult and suggests that this is an unattainable goal. We demonstrate that residual glandular tissue is significantly higher in skin flaps > 5 mm in comparison to skin flaps ≤ 5 mm, and that residual glandular tissue increases significantly already when the flap thickness exceeds 7 mm.

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  • 8.
    Andersén, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Dahlquist, Gisela
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Damber, Jan-Erik
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Hjemdahl, Paul
    Korsgren, Olle
    Olsson, Håkan
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Svensk medicinsk forskning behöver inte mer styrning2014Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 22-23, s. 980-981Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 9.
    Anerillas, Luis Oliveros
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Kingham, Paul J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lammi, Mikko
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Kelk, Peyman
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Three-dimensional osteogenic differentiation of bone marrow mesenchymal stem cells promotes matrix metallopeptidase 13 (Mmp13) expression in type i collagen hydrogels2021Ingår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, nr 24, artikel-id 13594Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autologous bone transplantation is the principal method for reconstruction of large bone defects. This technique has limitations, such as donor site availability, amount of bone needed and morbidity. An alternative to this technique is tissue engineering with bone marrow-derived mesenchymal stem cells (BMSCs). In this study, our aim was to elucidate the benefits of culturing BMSCs in 3D compared with the traditional 2D culture. In an initial screening, we combined BMSCs with four different biogels: unmodified type I collagen (Col I), type I collagen methacrylate (ColMa), an alginate and cellulose-based bioink (CELLINK) and a gelatin-based bioink containing xanthan gum (GelXA-bone). Col I was the best for structural integrity and maintenance of cell morphology. Osteogenic, adipogenic, and chondrogenic differentiations of the BMSCs in 2D versus 3D type I collagen gels were investigated. While the traditional pellet culture for chondrogenesis was superior to our tested 3D culture, Col I hydrogels (i.e., 3D) favored adipogenic and osteogenic differentiation. Further focus of this study on osteogenesis were conducted by comparing 2D and 3D differentiated BMSCs with Osteoimage® (stains hydroxyapatite), von Kossa (stains anionic portion of phosphates, carbonates, and other salts) and Alizarin Red (stains Ca2+ deposits). Multivariate gene analysis with various covariates showed low variability among donors, successful osteogenic differentiation, and the identification of one gene (matrix metallopeptidase 13, MMP13) significantly differentially expressed in 2D vs. 3D cultures. MMP13 protein expression was confirmed with immunohistochemistry. In conclusion, this study shows evidence for the suitability of type I collagen gels for 3D osteogenic differentiation of BMSCs, which might improve the production of tissue-engineered constructs for treatment of bone defects.

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  • 10.
    Anerillas, Luis Oliveros
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Kingham, Paul J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Kelk, Peyman
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Platelet lysate for expansion or osteogenic differentiation of bone marrow mesenchymal stem cells for 3D tissue constructs2023Ingår i: Regenerative Therapy, E-ISSN 2352-3204, Vol. 24, s. 298-310Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The use of mesenchymal stem cells (MSCs) for the development of tissue-engineered constructs has advanced in recent years. However, future clinically approved products require following good manufacturing practice (GMP) guidelines. This includes using alternatives to xenogeneic-derived cell culture supplements to avoid rejection of the transplants. Consequently, human platelet lysate (PLT) has been adopted as an affordable and effective alternative to foetal bovine serum (FBS) in traditional 2D cultures. However, little is known about its effect in more advanced 3D culture systems.

    Methods: We evaluated bone marrow MSCs (BMSCs) proliferation and CD marker expression in cells expanded in FBS or PLT-supplemented media. Differentiation capacity of the BMSCs expanded in the presence of the different supplements was evaluated in 3D type I collagen hydrogels. Furthermore, the effects of the supplements on the process of differentiation were analyzed by using qPCR and histological staining.

    Results: Cell proliferation was greater in PLT-supplemented media versus FBS. BMSCs expanded in PLT showed similar osteogenic differentiation capacity in 3D compared with FBS expanded cells. In contrast, when cells were 3D differentiated in PLT they showed lower osteogenesis versus the traditional FBS protocol. This was also the case for adipogenic differentiation, in which FBS supplementation was superior to PLT.

    Conclusions: PLT is a superior alternative to FBS for the expansion of MSCs without compromising their subsequent differentiation capacity in 3D. However, differentiation in PLT is impaired. Thus, PLT can be used to reduce the time required to expand the necessary cell numbers for development of 3D tissue engineered MSC constructs.

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  • 11. Armstrong, Stephanie J.
    et al.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Kingham, Paul J
    ECM molecules mediate both Schwann cell proliferation and activation to enhance neurite outgrowth2007Ingår i: Tissue engineering, ISSN 1076-3279, E-ISSN 1557-8690, Vol. 13, nr 12, s. 2863-2870Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tissue engineering using a combination of biomaterials and cells represents a new approach to nerve repair. We have investigated the effect that extracellular matrix (ECM) molecules have on Schwann cell (SC) attachment and proliferation on the nerve conduit material poly-3-hydroxybutyrate (PHB), and SC influence on neurite outgrowth in vitro. Initial SC attachment to PHB mats was unaffected by ECM molecules but proliferation increased (laminin > fibronectin > collagen). SCs seeded onto ECM-coated culture inserts suspended above a monolayer of NG108-15 cells determined the effect of released diffusible factors. The effect of direct contact between the two cell types on ECM molecules was also investigated. In both systems SCs enhanced neurite number per cell and percentage of NG108-15 cells sprouting neurites. NG108-15 cells grown in direct contact with SCs had significantly longer neurites than those exposed to diffusible factors when seeded on laminin or fibronectin. Diffusible factors released from SCs cultured on ECM molecules appear to initiate neurite outgrowth, whereas SC-neuron contact promotes neurite elongation. SC proliferation was maximal on poly-D-lysine-coated surfaces, but these cells did not influence neurite outgrowth to the levels of laminin or fibronectin. This suggests that ECM molecules enhance cell number and activate SCs to release neurite promoting factors. Addition of ECM molecules to PHB nerve conduits containing SCs is likely to provide benefits for the treatment of nerve injuries.

  • 12. Armstrong, Stephanie J
    et al.
    Wiberg, Mikael
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi. Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Kingham, Paul J
    Laminin activates NF-kappaB in Schwann cells to enhance neurite outgrowth.2008Ingår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 439, nr 1, s. 42-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Extracellular matrix (ECM) molecules and Schwann cells (SCs) are important components of peripheral nerve regeneration. In this study, the role of the transcription factor nuclear factor kappa B (NF-kappaB) in SC activation in response to laminin and the subsequent effect on in vitro neurite outgrowth was investigated. Immunocytochemistry and Western blot analysis showed that compared with poly-d-lysine (PDL), laminin enhanced the phosphorylation of IkappaB and p65 NF-kappaB signalling proteins in SCs. Phospho NF-kappaB-p65 was localised to the nucleus indicating activation of NF-kappaB. To assess the functional effect of NF-kappaB activation, SCs plated on PDL or laminin were pre-treated with NF-kappaB inhibitors, 6-amino-4-(4-phenoxyphenylethylamino)quinazoline (QNZ) or Z-leu-leu-leu-CHO (MG-132) before NG108-15 neuronal cells were seeded on the SC monolayer. After 24h co-culture in the absence of inhibitors, SCs seeded on laminin enhanced the mean number and length of neurites extended by NG108-15 cells (1.87+/-0.13 neurites; 238.74+/-8.53microm) compared with those cultured in the presence of SCs and PDL (1.26+/-0.07 neurites; 157.57+/-9.80microm). At 72h, neurite length had further increased to 321.83+/-6.60microm in the presence of SCs and laminin. Inhibition of NF-kappaB completely abolished the effect of laminin on SC evoked neurite outgrowth at 24h and reduced the enhancement of neurite length by over 60% at 72h. SC proliferation was unaffected by NF-kappaB inhibition suggesting that the NF-kappaB signalling pathway plays a discrete role in the activation of SCs and their neurotrophic potential.

  • 13.
    Backman, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Cold finger1993Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Post Traumatic Cold Intolerance is the most common, and often the most prominent disabilityfrom hand trauma. The discomfort caused by cold is believed to be linked to a dysfunction o f thedigital vasoregulation, but its pathophysiology is poorly understood. Cold induced vasospasm, i.e.the pathologically increased reactivity o f the digital vessels to cold, is commonly found in handsthat have sustained trauma, especially with damage to vascular and neural structures.

    This thesis is based upon a series o f clinical and laboratory studies on cold induced vasospasm andcold intolerance in 35 patients treated for digital amputation. The replanted digit was used as astudy model, since it represents a body part which at the moment o f reconstruction is devoid o f allinnervation. Replantations were performed according to two different principles o f vascularreconstruction; using long or short vessel grafts. Finger Systolic Pressure (FSP) was used as aparameter o f digital vasoregulation at different temperatures, and cold intolerance was assessedusing a logarithmic rating scale (Borg). Non-injured fingers and amputation stumps were used ascontrols. Clinical and laboratory investigations were performed at different intervals from oneweek to three years after the reconstruction.

    During the first two weeks following replantation, whole body cold exposure, or cooling o f thereplanted part to 10°C, did not cause serious spasm in the replanted vessels. Follow upinvestigations demonstrated that a cold related vasospastic tendency is established inapproximately 60% o f the replanted parts within one year after trauma. The once establishedpathologic vasoregulation, is unlikely to normalize spontaneously. Whether a cold related arterialspasticity will develop in the replanted digit or not, is not related to the surgeon's choice o ftechnique for vascular reconstruction. Cold related arterial spasticity was more common inamputation stumps than in replanted digits, Our findings suggest that there is a pathologicalreaction to cold in the distal palm vessels but the nature o f this disturbance is not clear.

    All patients developed some degree o f Post Traumatic Cold Intolerance. Approximately 60% o fthe patients stated that some improvement took place, but none o f the patients was free o f coldintolerance 1-7 years after the injury. Patients with a pathological cold induced vasospasm is likelyto present with severe cold intolerance, which indicates that the vasospasm is involved as one o fthe causes o f Post Traumatic Cold Intolerance.

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  • 14.
    Backman, Olof
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Bruze, Gustaf
    Naslund, Ingmar
    Ottosson, Johan
    Marsk, Richard
    Neovius, Martin
    Naslund, Erik
    Gastric Bypass Surgery Reduces De Novo Cases of Type 2 Diabetes to Population Levels A Nationwide Cohort Study From Sweden2019Ingår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 269, nr 5, s. 895-902Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aim of this study was to determine long-term changes in pharmacological treatment of type 2 diabetes after primary Roux-en-Y gastric bypass (RYGB) surgery, in patients with and without pharmacological treatment of diabetes preoperatively.

    Summary of Background Data: Several studies have shown that gastric bypass has good effect on diabetes, at least in the short-term. This study is a nationwide cohort study using Swedish registers, with basically no patients lost to follow-up during up to 7 years after surgery.

    Methods: The effect of RYGB on type 2 diabetes drug treatment was evaluated in this nationwide matched cohort study. Participants were 22,047 adults with BMI ≥30 identified in the nationwide Scandinavian Surgical Obesity Registry, who underwent primary RYGB between 2007 and 2012. For each individual, up to 10 general population comparators were matched on birth year, sex, and place of residence. Prescription data were retrieved from the nationwide Swedish Prescribed Drug Register through September 2015. Incident use of pharmacological treatment was analyzed using Cox regression.

    Results: Sixty-seven percent of patients with pharmacological treatment of type 2 diabetes before surgery were not using diabetes drugs 2 years after surgery and 61% of patients were not pharmacologically treated up to 7 years after surgery. In patients not using diabetes drugs at baseline, there were 189 new cases of pharmacological treatment of type 2 diabetes in the surgery group and 2319 in the matched general population comparators during a median follow-up of 4.6 years (incidence: 21.4 vs 27.9 per 10,000 person-years; adjusted hazard ratio 0.77, 95% confidence interval 0.67–0.89; P < 0.001).

    Conclusions: Gastric bypass surgery not only induces remission of pharmacological treatment of type 2 diabetesbut also protects from new onset of pharmacological diabetes treatment. The effect seems to persist in most, but not all, patients over 7 years of follow-up.

  • 15.
    Backman, Olof
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Freedman, Jacob
    Marsk, Richard
    Nilsson, Henrik
    Laparoscopic Roux-en-Y Gastric Bypass Without Division of the Mesentery Reduces the Risk of Postoperative Complications2019Ingår i: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 33, nr 9, s. 2858-2863Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Anastomotic complications after laparoscopic Roux-en-Y gastric bypass (LRYGB) including leaks, ulceration, and stenosis remain a significant cause of post-operative morbidity and mortality. Our objective was to compare two different surgical techniques regarding short-term anastomotic complications.

    Methods: A retrospective analysis of all patients operated with a primary LRYGB from 2006 to June 2015 in one institution, where prospectively collected data from an internal quality registry and medical journals were analyzed.

    Results: In total, 2420 patients were included in the analysis. 1016 were operated with a technique where the mesentery was divided during the creation of the Roux-limb (DM-LRYGB) and 1404 were operated with a method where the mesentery was left intact (IM-LRYGB). Leakage in the first 30 days [2.6% vs. 1.1% (p < 0.05)], and ulceration or stenosis occurring during the first 6 months after surgery [5.6% vs. 0.1% (p < 0.05)] was significantly higher in the DM-LRYGB group. Adjusted odds ratio for anastomotic leak was 0.46 (95% CI 0.24-0.87) and for stenosis/ulceration 0.01 (95% CI 0.002-0.09).

    Conclusion: IM-LRYGB seems to reduce the risk of complications at the anastomosis. A plausible explanation for this is that the blood supply to the anastomosis is compromised when the mesentery is divided.

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  • 16.
    Blaszczyk, Izabela
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Upper limb assessment and treatment in cerebral palsy2023Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Cerebral palsy (CP) is a heterogeneous group of neurological disorders caused by fetal or infant brain damage that often involves deficits in upper limb (UL) posture and function. Knowledge about effective methods of assessment and treatment of UL in CP is not extensive. In this thesis, different aspects of these two are explored.

    In Paper I we retrospectively investigated the effect of a long-term treatment regime developed in Västerbotten county habilitation service. The treatment regime included intramuscular injections of botulinum toxin type A (BoNT-A) combined with occupational therapy (OT) and movement training. The results of passive extension of the wrist with fingers extended and the assessment of hand function in children with severe hand function impairment (initially House functional classification 0-1) were analyzed over time. Twenty-five children were divided into 3 groups depending on the treatment regime start age (before or after the age of 7) and treatment regime availability. We found significantly worse passive extension of the wrist with fingers extended in children who did not have a chance to benefit from therapy in early childhood. Additionally, an improvement in the passive movement of the wrists was noted in children who completed the treatment regime before the age of 7. Regarding hand function, a significant difference was found between children who received treatment in early childhood and those who received treatment as adolescents.

    The injections of BoNT-A in CP are common, however the monitoring of eventual side effects and adverse events (AEs) after this treatment is difficult to perform in clinical practice. To facilitate this process, we created a new, no previously validated questionnaire (Paper II). The questionnaire was given to patients or their caregivers to be completed after each BoNT-A treatment. 94% of participants returned the questionnaire. 80 % were filled in completely which proves the effectiveness of the applied form and the ease of its use in clinical practice. 61% of patients reported one or more different AEs or sides effects. In addition, we analyzed the risk for generalized and focal distal AEs reported by 38% of patients. Those may indicate the spread of BoNT-A toxin to the whole body, therefore requiring special attention. We found that females had a 1.899 relative risk with significant association (p=0.029) of reporting generalized and focal delayed AEs compared to males. The use of the questionnaire helped to make the decision to change or discontinue BoNT-A injections in 8 cases (11%).

    In some patients with dyskinetic type of CP (DCP) treated with BoNT-A to diminish the external rotation posture of the shoulders, a loss of treatment effect was observed, which contributed to the need to look for another method of treatment. In paper III, a surgical method to manage the external rotation posture of the shoulders is presented. The surgical procedure consists of weakening the strength of the externally rotating muscles by cutting the attachment of one of them (release of the posterior deltoid) and complete denervation of the other (denervation of the infraspinatus). The third shoulder external rotator (teres minor) remains intact. The results of this procedure performed in 7 shoulders in 6 patients (age 14-24) were analyzed using satisfaction questionnaire and pre-/postoperative video-recordings. Five of 6 patients were very satisfied with the treatment, one was neither satisfied nor dissatisfied. Four patients had an obvious improvement in their shoulder position confirmed on video recordings. In one, overcorrection in the form of internal shoulder rotation was observed.

    Assessment of the thumb in CP is important as the thumb impairment plays a crucial role in hand grip function. Paper IV presents a new tool called CP-thumb score, which addresses the occupational therapists to follow the changes in the thumb function and its posture. CP-thumb score has two parts: descriptive and score of the thumb’s CMC joint radial abduction. Thirty thumbs in 19 patients with all types of CP were assessed with CP-thumb score. All assessments were made based on available video recordings. Additionally, all thumbs were assessed using the House’s thumb-in-palm classification which has been shown to be unreliable. These two thumb assessments were compared with each other.

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  • 17.
    Blaszczyk, Izabela
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Nordell, Sara
    Habilitation Centre, Västerbotten County Council, Umeå, Sweden.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Cp-thumb score - a new assessment of the thumb deformity in cerebral palsy: a pilot studyManuskript (preprint) (Övrigt vetenskapligt)
  • 18.
    Boivie, Patrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Hedberg, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Engström, Karl Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Size distribution of embolic material produced at aortic cross-clamp manipulation2010Ingår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 44, nr 6, s. 367-372Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The association between aortic atherosclerosis and neurological damage during cardiac surgery is well recognized. The purpose was here to analyze the size distribution of particles produced at cross-clamp manipulation of the ascending aorta.

    Design: A human cadaveric aortic perfusion model of retrograde design was applied (n 27). With this model, washout samples were collected from the pressurized ascending aorta during cross clamp manipulation. Before the experiment, the aorta was flushed to remove debris and with a baseline sample collected. The cross-clamp was opened to collect ten repeated aliquots with dislodged particles. Collected washout samples were evaluated by digital image analysis and microscopy.

    Results: Cross-clamping produced a significant output of particles, which was seen for size intervals of 1 mm and smaller (p 0.002 to p 0.022). In all size intervals the particle output correlated with the degree of overall aortic calcification(p 0.002 to p 0.025). The model generated substantially more small-size particles than large debris (p 0.010).

    Conclusions: Aortic clamping was here verified to dislodge aortic debris which correlated with the degree of observed calcification. Macroscopic particles were few. In contrast, cross-clamping produced substantial numbers of small-size particles. These findings emphasize microembolic risks associated with cross-clamping of atherosclerotic vessels.

  • 19.
    Bozaghian, Sadaf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Professionell utveckling.
    McGrath, Aleksandra M
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Professionell utveckling.
    Karlsson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Professionell utveckling.
    Evidensbaserad konsultation som får plats i fickan2020Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 117, artikel-id FXP7Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 20.
    Bremell, Rakel
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Osteomyelit – diagnos och behandling av patienter som genomgår trycksårsoperation2020Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 21.
    Brohlin, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Mesenchymal stem cells for repair of the peripheral and central nervous system2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Bone marrow-derived mesenchymal stem cells (MSC) have been shown to provide neuroprotection after transplantation into the injured nervous system. The present thesis investigates whether adult human and rat MSC differentiated along a Schwann cell lineage could increase their expression of neurotrophic factors and promote regeneration after transplantation into the injured peripheral nerve and spinal cord.

    Human and rat mesenchymal stem cells (hMSC and rMSC) expressed characteristic stem cell surface markers, mRNA transcripts for different neurotrophic factors and demonstrated multi-lineage differentiation potential. Following treatment with a cocktail of growth factors, the hMSC and rMSC expressed typical Schwann cells markers at both the transcriptional and translational level and significantly increased production of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF).

    Age and time in culture are of relevance for clinical settings and growth-promoting effects of hMSC from young donors (16-18 years) and old donors (67-75 years) were compared. Undifferentiated hMSC from both young and old donors increased total neurite length of cultured dorsal root ganglion (DRG) neurons. Differentiation of hMSC from the young donors, but not the eldery donors, further enhanced the neurite outgrowth. Undifferentiated hMSC were cultured for eleven weeks in order to examine the effect of in vitro expansion time on neurite outgrowth. hMSC from the young donors maintained their proliferation rate and their ability to enhance neurite outgrowth from DRG neurons.

    Using a sciatic nerve injury model, a 10mm gap was bridged with either an empty tubular fibrin glue conduit, or conduits containing hMSC, with and without cyclosporine treatment. Cells were labeled with PKH26 prior to transplantation. At 3 weeks after injury the conduits with cells and immunosuppression increased regeneration compared with an empty conduit. PKH26 labeled human cells survived in the rat model and the inflammatory reaction could be suppressed by cyclosporine.

    After cervical C4 hemisection, BrdU/GFP-labeled rMSC were injected into the lateral funiculus rostral and caudal to the spinal cord lesion site. Spinal cords were analyzed 2-8 weeks after transplantation. Transplanted MSC remained at the injection sites and in the trauma zone for several weeks and were often associated with numerous neurofilament-positive axons. Transplanted rMSC induced up-regulation of vascular endothelial growth factor in spinal cord tissue rostral to the injury site, but did not affect expression of brain-derived neurotrophic factor. Although rMSC provided neuroprotection for rubrospinal neurons and significantly attenuated astroglial and microglial reaction, cell transplantation caused aberrant sprouting of calcitonin gene-related peptide immunostained sensory axons in the dorsal horn.

    In summary these results demonstrate that both rat and human MSC can be differentiated towards the glial cell lineage, and show functional characteristics similar to Schwann cells. hMSC from the young donors represent a more favorable source for neurotransplantation since they maintain proliferation rate and preserve their growth-promoting effects in long-term cultures. The data also suggest that differentiated MSC increase expression of neurotrophic factors and support regeneration after peripheral nerve and spinal cord injury.

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    Brohlin 2011
  • 22.
    Brohlin, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Kelk, Peyman
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Kingham, Paul J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Effects of a defined xeno-free medium on the growth and neurotrophic and angiogenic properties of human adult stem cells2017Ingår i: Cytotherapy, ISSN 1465-3249, E-ISSN 1477-2566, Vol. 19, nr 5, s. 629-639Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. The growth properties and neurotrophic and angiogenic effects of human mesenchymal stromal cells (MSCs) cultured in a defined xeno-free, serum-free medium (MesenCult-XF) were investigated. Methods. Human MSCs from adipose tissue (ASCs) and bone marrow (BMSCs) were cultured in Minimum Essential Medium-alpha (alpha-MEM) containing fetal calf serum or in MesenCult-XF. Proliferation was measured over 10 passages and the colony-forming unit (CFU) assay and expression of cluster of differentiation (CD) surface markers were determined. Neurite outgrowth and angiogenic activity of the MSCs were determined. Results. At early passage, both ASCs and BMSCs showed better proliferation in MesenCult-XF compared with standard a-MEM containing serum. However, CFUs were significantly lower in MesenCult-XF. ASCs cultured in MesenCult-XF continued to expand at faster rates than cells grown in serum. BMSCs showed morphological changes at late passage in MesenCult-XF and stained positive for senescence beta-galactosidase activity. Expression levels of CD73 and CD90 were similar in both cell types under the various culture conditions but CD105 was significantly reduced at passage 10 in MesenCult-XF. In vitro stimulation of the cells enhanced the expression of brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF-A) and angiopoietin-1. Stimulated ASCs grown in MesenCult-XF evoked the longest neurite outgrowth in a neuron co-culture model. Stimulated BMSCs grown in MesenCult-XF produced the most extensive network of capillary-like tube structures in an in vitro angiogenesis assay. Conclusions. ASCs and BMSCs exhibit high levels of neurotrophic and angiogenic activity when grown in the defined serum free medium indicating their suitability for treatment of various neurological conditions. However, long-term expansion in MesenCult-XF might be restricted to ASCs.

  • 23.
    Brohlin, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kingham, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikova, Liudmila
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikov, Lev
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Aging effect on neurotrophic activity of human mesenchymal stem cells2012Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 7, nr 9, s. e45052-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Clinical efficacy of stem cells for nerve repair is likely to be influenced by issues including donor age and in vitro expansion time. We isolated human mesenchymal stem cells (MSC) from bone marrow of young (16–18 years) and old (67–75 years) donors and analyzed their capacity to differentiate and promote neurite outgrowth from dorsal root ganglia (DRG) neurons. Treatment of MSC with growth factors (forskolin, basic fibroblast growth factor, platelet derived growth factor-AA and glial growth factor-2) induced protein expression of the glial cell marker S100 in cultures from young but not old donors. MSC expressed various neurotrophic factor mRNA transcripts. Growth factor treatment enhanced the levels of BDNF and VEGF transcripts with corresponding increases in protein release in both donor cell groups. MSC in co-culture with DRG neurons significantly enhanced total neurite length which, in the case of young but not old donors, was further potentiated by treatment of the MSC with the growth factors. Stem cells from young donors maintained their proliferation rate over a time course of 9 weeks whereas those from the old donors showed increased population doubling times. MSC from young donors, differentiated with growth factors after long-term culture, maintained their ability to enhance neurite outgrowth of DRG. Therefore, MSC isolated from young donors are likely to be a favourable cell source for nerve repair.

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  • 24.
    Brohlin, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Mahay, Daljeet
    Novikov, Lev N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Terenghi, Giorgio
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Shawcross, Susan G
    Novikova, Liudmila N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Characterisation of human mesenchymal stem cells following differentiation into Schwann cell-like cells2009Ingår i: Neuroscience research, ISSN 0168-0102, E-ISSN 1872-8111, Vol. 64, nr 1, s. 41-49Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cell-based therapies provide a clinically applicable and available alternative to nerve autografts. Our previous studies have characterised rat-derived mesenchymal stem cells (MSC) and here we have investigated the phenotypic, molecular and functional characteristics of human-derived MSC (hMSC) differentiated along a Schwann cell lineage. The hMSC were isolated from healthy human donors and the identity of the undifferentiated hMSC was confirmed by the detection of MSC specific cells surface markers. The hMSC were differentiated along a glial cell lineage using an established cocktail of growth factors including glial growth factor-2. Following differentiation, the hMSC expressed the key Schwann cell (SC) markers at both the transcriptional and translational level. More importantly, we show the functional effect of hMSC on neurite outgrowth using an in vitro co-culture model system with rat-derived primary sensory neurons. The number of DRG sprouting neurites was significantly enhanced in the presence of differentiated hMSC; neurite length and density (branching) were also increased. These results provide evidence that hMSC can undergo molecular, morphological and functional changes to adopt a SC-like behaviour and, therefore, could be suitable as SC substitutes for nerve repair in clinical applications.

  • 25. Caddick, Jenny
    et al.
    Kingham, Paul J
    Gardiner, Natalie J
    Wiberg, Mikael
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi. Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Phenotypic and functional characteristics of mesenchymal stem cells differentiated along a Schwann cell lineage.2006Ingår i: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 54, nr 8, s. 840-849Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have investigated the phenotypic and bioassay characteristics of bone marrow mesenchymal stromal cells (MSCs) differentiated along a Schwann cell lineage using glial growth factor. Expression of the Schwann cell markers S100, P75, and GFAP was determined by immunocytochemical staining and Western blotting. The levels of the stem cell markers Stro-1 and alkaline phosphatase and the neural progenitor marker nestin were also examined throughout the differentiation process. The phenotypic properties of cells differentiated at different passages were also compared. In addition to a phenotypic characterization, the functional ability of differentiated MSCs has been investigated employing a co-culture bioassay with dissociated primary sensory neurons. Following differentiation, MSCs underwent morphological changes similar to those of cultured Schwann cells and stained positively for all three Schwann cell markers. Quantitative Western blot analysis showed that the levels of S100 and P75 protein were significantly elevated upon differentiation. Differentiated MSCs were also found to enhance neurite outgrowth in co-culture with sensory neurons to a level equivalent or superior to that produced by Schwann cells. These findings support the assertion that MSCs can be differentiated into cells that are Schwann cell-like in terms of both phenotype and function.

  • 26. Chin, K. Y.
    et al.
    Hart, A. M.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Temporary catheter first perfusion during hand replantation with prolonged warm ischaemia2012Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1878-0539, Vol. 65, nr 5, s. 675-677Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Since the first successful arm replantation reported by Malt and McKhann in 1962, developments and refinements to upper extremity replantation techniques have led to higher success rates with better functional outcomes. One of the most important determinants of a successful macroreplantation is the ischaemic time of the amputated part, as irreversible muscle necrosis begins after 6 hours of warm ischaemia. With major trauma and plastic surgery units usually covering a wide geographical area, it is often difficult to ensure patient injury to revascularization time is less than 6 hours. In 1981, Nunley et al described the temporary catheter perfusion technique in upper limb replantation surgery to reduce ischaemia time without any significant complications. When used in appropriate cases this technique can reduce complication rates in upper limb replantation surgeries. Material and methods: Temporary catheter first perfusion was used in a hand replantation after 6 hours of warm ischaemia, with preservation of the intrinsic muscles, as evidenced by return of function. The technique used is described, along with relevant literature. Results: Temporary catheter perfusion allowed early reperfusion of the amputated hand, improving the chance of intrinsic muscle preservation despite delayed presentation. It allowed better wound evaluation and debridement, and facilitated better bone stabilisation prior to vascular repair. Conclusion: Temporary catheter perfusion is well described in proximal upper limb replantation procedures. This case shows that it is also a useful adjunct for hand replantation, particularly when the patient presents with a critical duration of warm ischaemia. (C) 2011 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.

  • 27.
    Chin, Kuen Yeow
    et al.
    Burns and Plastic Surgery, Canniesburn Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
    El-Kayat, Bara
    Burns and Plastic Surgery, Canniesburn Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
    Milne, Alistair
    Department of Pathology, Crosshouse Hospital, Kilmarnock, United Kingdom.
    Hart, Andrew
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Burns and Plastic Surgery, Canniesburn Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom; College of Medical, Veterinary and Life Sciences, The University of Glasgow, University Avenue, Glasgow, United Kingdom.
    Melanoma diagnosed 27 years after a benoxaprofen-induced photosensitivity reaction2012Ingår i: Journal of Dermatological Case Reports, E-ISSN 1898-7249, Vol. 6, nr 1, s. 5-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The propionic acid derivative Benoxaprofen was introduced for the treatment of rheumatic disorders in 1980. Its product license was then withdrawn2 years later due to concerns over serious dermatologic, hepatic and renal side effects. Photosensitivity was the most common side effect with reported incidence of up to 50%.

    Main observations: We present the first case report of a patient who presented with a melanoma diagnosed 27 years after a benoxaprofen-induced photosensitivity reaction. With an estimated 1.5 million patients previously on benoxaprofen, a large number of patients may potentially face increased risk of developing malignant melanoma. This case report can only suggest an association between solar injury secondary to benoxaprofen-related photosensitivity and subsequent melanoma. However the primary factor that improves survival from melanoma is early diagnosis, and so clinicians treating this group of patients should be aware of this risk.

    Conclusion: Although benoxaprofen is no longer in clinical use, the long-term sequelae to its photosensitizing effects may still be clinically important. Clinicians treating this group of patients should be vigilant, and consider a low threshold for diagnostic biopsy of suspicious skin lesions.

  • 28.
    Ching, Rosanna C.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Kingham, Paul J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Schwann cell-like differentiated adipose stem cells promote neurite outgrowth via secreted exosomes and RNA transfer2018Ingår i: Stem Cell Research & Therapy, E-ISSN 1757-6512, Vol. 9, artikel-id 266Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Adipose derived stem cells can be stimulated to produce a growth factor rich secretome which enhances axon regeneration. In this study we investigated the importance of exosomes, extracellular vesicles released by many different cell types, including stem cells and endogenous nervous system Schwann cells (SCs), on neurite outgrowth.

    Methods: Adipose derived stem cells were differentiated towards a Schwann cell-like phenotype (dADSCs) by in vitro stimulation with a mix of factors (basic fibroblast growth factor, platelet derived growth factor-AA, neuregulin-1 and forskolin). Using a precipitation and low-speed centrifugation protocol the extracellular vesicles were isolated from the medium of the stem cells cultures and also from primary SCs. The conditioned media or concentrated vesicles were applied to neurons in vitro and computerised image analysis was used to assess neurite outgrowth. Total RNA was purified from the extracellular vesicles and investigated using qRT-PCR.

    Results: Application of exosomes derived from SCs significantly enhanced in vitro neurite outgrowth and this was replicated by the exosomes from dADSCs. qRT-PCR demonstrated that the exosomes contained mRNAs and miRNAs known to play a role in nerve regeneration and these molecules were up-regulated by the Schwann cell differentiation protocol. Transfer of fluorescently tagged exosomal RNA to neurons was detected and destruction of the RNA by UV-irradiation significantly reduced the dADSCs exosome effects on neurite outgrowth. In contrast, this process had no significant effect on the SCs-derived exosomes.

    Conclusions: In summary, this work suggests that stem cell-derived exosomes might be a useful adjunct to other novel therapeutic interventions in nerve repair.

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  • 29.
    Christensen, Jens
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin. UCLH, ISEH, London, England; Pure Sports Clin, London, England.
    Andersson, Gustav
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Protease-activated receptors in the Achilles tendon-a potential explanation for the excessive pain signalling in tendinopathy2015Ingår i: Molecular Pain, E-ISSN 1744-8069, Vol. 11, artikel-id 13Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aim: Tendinopathies are pathological conditions of tissue remodelling occurring in the major tendons of the body, accompanied by excessive nociceptive signalling. Tendinopathies have been shown to exhibit an increase in the number of mast cells, which are capable of releasing histamine, tryptase and other substances upon activation, which may play a role in the development of tendinopathies. This study set out to describe the distribution patterns of a family of receptors called protease-activated receptors (PARs) within the Achilles tendon. These four receptors (PAR1, PAR2, PAR3, PAR4) are activated by proteases, including tryptase released from mast cells, and are involved in fibrosis, hyperalgesia and neovascularisation, which are changes seen in tendinopathies. Method: In order to study which structures involved in tendinopathy that these proteases can affect, biopsies from patients suffering of mid-portion Achilles tendinosis and healthy controls were collected and examined using immunohistochemistry. Tendon cells were cultured to study in vitro expression patterns. Results: The findings showed a distribution of PARs inside the tendon tissue proper, and in the paratendinous tissue, with all four being expressed on nerves and vascular structures. Double staining showed co-localisation of PARs with nociceptive fibres expressing substance P. Concerning tenocytes, PAR2, PAR3, and PAR4, were found in both biopsies of tendon tissue and cultured tendon cells. Conclusions: This study describes the expression patterns of PARs in the mid-portion of the Achilles tendon, which can help explain the tissue changes and increased pain signalling seen in tendinopathies. These findings also show that in-vitro studies of the effects of these receptors are plausible and that PARs are a possible therapeutic target in the future treatment strategies of tendinopathy.

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  • 30.
    Constantinou, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Bedömning av velofaryngeal dynamik genom videoradiografisk undersökning: en valideringsstudie2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 31.
    Cotrufo, Stefano
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Canniesburn Plastic Surgery Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom; .
    Dabernig, Joerg
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Canniesburn Plastic Surgery Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom; Laboratory of Human Anatomy, University of Glasgow, Glasgow, United Kingdom.
    Russell, David
    Laboratory of Human Anatomy, University of Glasgow, Glasgow, United Kingdom.
    Payne, Anthony
    Laboratory of Human Anatomy, University of Glasgow, Glasgow, United Kingdom.
    Hart, Andrew
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Canniesburn Plastic Surgery Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom; .
    The Vascular Anatomy of the Rat Superficial Epigastric Flap by Vascular Corrosion Casting and Technical Refinement for the Study of Choke Vessels in Cadaveric Flap Models2010Ingår i: Annals of Plastic Surgery, ISSN 0148-7043, E-ISSN 1536-3708, Vol. 64, nr 1, s. 93-97Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Accurate depiction of cutaneous vascular microanatomy is of relevance to plastic surgical flap research, and to descriptive anatomy. Yet current techniques have not permitted full visualization of the subdermal plexus, or potential angiosomal connections. Nor has endothelial visualization been facilitated. Vascular corrosion casting techniques are promising in that regard, and were applied in an extended lateral thoracoabdominal suprafascial adipocutancous flap in the rat (based on the superficial epigastric bundle). Technical refinements for application to further study of human cadaveric flap models are presented. The intraflap vascular branching pattern of the superficial epigastric artery is described, with filling of the lateral thoracic, intercostals, and iliolumbar angiosomes found when coagulation of vessels at the periphery was delayed until after clearance. The vascular casting protocol presented is an effective and promising tool for the study of macro- and microvascular anatomy.

  • 32.
    Dabernig, Jörg
    et al.
    Glasgow Royal Infirmary.
    Ong, Keh O
    Glasgow Royal Infirmary.
    McGowan, Robert
    Glasgow Royal Infirmary.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Payne, Anthony P
    University of Glasgow.
    Hart, Andrew M
    Glasgow Royal Infirmary.
    The anatomic and radiologic basis of the circumflex scapular artery perforator flap2010Ingår i: Annals of Plastic Surgery, ISSN 0148-7043, E-ISSN 1536-3708, Vol. 64, nr 6, s. 784-788Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Microsurgical development has recently focused upon the perforator paradigm and primary thinning. Existing perforator flaps may require intramuscular dissection or lack reliable surface markings, whereas traditional scapular/parascapular flaps have low donor morbidity and reliable anatomy, but can be excessively bulky. Clinical application of a new flap based on a perforator from the circumflex scapular axis (CSA) has recently been published, but the vessel's anatomy has not been adequately characterized. The CSA was dissected in 115 sites in 69 cadavers. The number, external vessel diameter, and site of origin of perforators were measured relative to the CSA bifurcation. Color Doppler ultrasound was used to delineate the CSA and its perforators bilaterally in 40 volunteers. The number, origin relative to CSA bifurcation, diameter, length, and flow velocity of cutaneous perforators were determined. A CSA perforator was always present, running into the subdermal plexus, arising within 2.4 cm of the bifurcation. Cadaver studies: mean perforator diameter, 1.3 mm (SD, 0.66); 13% arose at bifurcation, 36% arose proximal (mean, 1.1 mm; SD, 0.63), and 52% distal to bifurcation (mean, 1.5 mm; SD, 0.88). Ultrasound: mean perforator diameter, 1.18 mm (SD, 0.41); mean flow velocity, 16.3 cm/s (SD, 3.65); perforator arose in 36% proximal, in 40% distal to bifurcation, and in 24% from the bifurcation. We definitively describe the anatomy of the perforator from the circumflex scapular artery upon which a new flap has been based. Its origin and dimensions are anatomically and radiologically reliable. The flap has certain potential benefits over existing perforator flaps.

  • 33.
    Dabernig, Jörg
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Sorensen, K
    Shaw-Dunn, J
    Hart, Andrew McKay
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    The thin circumflex scapular artery perforator flap2007Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1878-0539, Vol. 60, nr 10, s. 1082-1096Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The development of microsurgery has most recently been focused upon the evolution of perforator flaps, with the aim of minimising donor site morbidity, and avoiding the transfer of functionally unnecessary tissues. The vascular basis of perforator flaps also facilitates radical primary thinning prior to flap transfer, when appropriate. Based upon initial clinical observations, cadaveric, and radiological studies, we describe a new, thin, perforator flap based upon the circumflex scapular artery (CSA). A perforator vessel was found to arise within 1.5cm of the CSA bifurcation (arising from the main trunk, or the descending branch). The perforator arborises into the sub-dermal vascular plexus of the dorsal scapular skin, permitting the elevation and primary thinning of a skin flap. This thin flap has been employed in a series of five clinical cases to reconstruct defects of the axilla (two cases of hidradenitis suppurativa; pedicled transfers), and upper limb (one sarcoma, one brachial to radial artery flowthrough revascularisation plus antecubital fossa reconstruction, and one hand reconstruction with a chimeric flap incorporating vascularised bone, fascia, and thin skin flaps; free tissue transfers). No intramuscular perforator dissection is required; pedicle length is 8-10cm and vessel diameter 2-4mm. There was no significant peri-operative complication or flap failure, all donor sites were closed primarily, patient satisfaction was high, and initial reconstructive aims were achieved in all cases. Surgical technique, and the vascular basis of the flap are described. The thin circumflex scapular artery perforator flap requires no intramuscular dissection yet provides high quality skin (whose characteristics can be varied by orientation of the skin paddle), and multiple chimeric options. The donor site is relatively hair-free, has favourable cosmesis and no known functional morbidity. This flap represents a promising addition to the existing range of perforator flaps.

  • 34. Dahlin, Lars B.
    et al.
    Andersson, Gert
    Backman, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Department of Hand Surgery, University Hospital of Northern Sweden, Umeå University, Umeå, Sweden.
    Svensson, Hampus
    Bjorkman, Anders
    Rehabilitation, Using Guided Cerebral plasticity, of a Brachial plexus Injury treated with Intercostal and phrenic Nerve transfers2017Ingår i: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 8, artikel-id 72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recovery after surgical reconstruction of a brachial plexus injury using nerve grafting and nerve transfer procedures is a function of peripheral nerve regeneration and cerebral reorganization. A 15-year-old boy, with traumatic avulsion of nerve roots C5-C7 and a non-rupture of C8-T1, was operated 3 weeks after the injury with nerve transfers: ( a) terminal part of the accessory nerve to the suprascapular nerve, (b) the second and third intercostal nerves to the axillary nerve, and (c) the fourth to sixth intercostal nerves to the musculocutaneous nerve. A second operation-free contralateral gracilis muscle transfer directly innervated by the phrenic nerve-was done after 2 years due to insufficient recovery of the biceps muscle function. One year later, electromyography showed activation of the biceps muscle essentially with coughing through the intercostal nerves, and of the transferred gracilis muscle by deep breathing through the phrenic nerve. Voluntary flexion of the elbow elicited clear activity in the biceps/gracilis muscles with decreasing activity in intercostal muscles distal to the transferred intercostal nerves (i.e., corresponding to eighth intercostal), indicating cerebral plasticity, where neural control of elbow flexion is gradually separated from control of breathing. To restore voluntary elbow function after nerve transfers, the rehabilitation of patients operated with intercostal nerve transfers should concentrate on transferring coughing function, while patients with phrenic nerve transfers should focus on transferring deep breathing function.

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  • 35.
    Dahlin, Lars B.
    et al.
    Institutionen för translationell medicin, Lunds universitet, Skånes universitetssjukvård, Malmö, Sweden.
    Arner, Marianne
    Handkirurgiska kliniken, Södersjukhuset, Stockholm, Sweden.
    Fredrikson, Per
    Hallands sjukhus, Halmstad, Sweden.
    Laurell, Tobias
    Handkirurgiska kliniken, Södersjukhuset, Stockholm, Sweden.
    Lindblom, Hans
    Södersjukhuset, Stockholm, Sweden.
    Sassu, Paolo
    Handkirurgiska kliniken, Sahlgrenska universitetssjukhuset, Göteborg, Germany.
    Wadström, Jonas
    Transplantationskirurgiska kliniken, Karolinska universitetssjukhuset, Huddinge, Sweden.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Handtransplantation snart verklighet i Sverige: [Hand transplantation in Sweden - preparations under way]2017Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, nr 39, artikel-id EM4IArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Some patients with a uni- or bilateral hand- or forearm amputation cannot use a hand prosthesis, although high-tech prostheses have been developed. A hand transplantation, particularly for those with bilateral amputations, may be an alternative solution. In a hand-transplanted patient, grip function, strength, sensibility and subsequent improved quality of life can be restored. Risks related to immunosuppression must be balanced by expected benefits, and thorough selection of patients has to be performed from both medical and psychological point of view. Therefore, a national network has been established in Sweden to achieve coordination with the needed competence.

  • 36. Dahlin, Lars B
    et al.
    Backman, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Düppe, Henrik
    Saito, Harukazu
    Chemnitz, Anette
    Abul-Kasim, Kasim
    Maly, Pavel
    Compression of the lower trunk of the brachial plexus by a cervical rib in two adolescent girls: case reports and surgical treatment.2009Ingår i: Journal of Brachial Plexus and Peripheral Nerve Injury, E-ISSN 1749-7221, Vol. 4, s. 14-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Presence of a cervical rib in children is extremely rare, particularly when symptoms of compression of the lower trunk of the brachial plexus occur. We present two cases with such a condition, where two young girls, 11 and 16 years of age were treated by resection of the cervical rib after a supraclavicular exploration of the lower trunk of the brachial plexus. The procedure led to successful results, objectively verified with tests in a work simulator, at one year follow-up.

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  • 37.
    di Summa, Pietro G
    et al.
    Chirurgie Plastique et Reconstructive CHUV, Université de Lausanne, Rue de Bugnon 46, 1005 Lausanne, CH, Switzerland.
    Kingham, Paul J
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Raffoul, W
    Chirurgie Plastique et Reconstructive CHUV, Université de Lausanne, Rue de Bugnon 46, 1005 Lausanne, CH, Switzerland.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Blond McIndoe Research Laboratories. The University of Manchester, Manchester, UK.
    Kalbermatten, Daniel F
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Adipose-derived stem cells enhance peripheral nerve regeneration2010Ingår i: Journal of plastic, reconstructive and aesthetic surgery, ISSN 1878-0539, Vol. 63, nr 9, s. 1544-1552Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Traumatic injuries resulting in peripheral nerve lesions often require a graft to bridge the gap. Although autologous nerve auto-graft is still the first-choice strategy in reconstructions, it has the severe disadvantage of the sacrifice of a functional nerve. Cell transplantation in a bioartificial conduit is an alternative strategy to create a favourable environment for nerve regeneration. We decided to test new fibrin nerve conduits seeded with various cell types (primary Schwann cells and adult stem cells differentiated to a Schwann cell-like phenotype) for repair of sciatic nerve injury. Two weeks after implantation, the conduits were removed and examined by immunohistochemistry for axonal regeneration (evaluated by PGP 9.5 expression) and Schwann cell presence (detected by S100 expression). The results show a significant increase in axonal regeneration in the group of fibrin seeded with Schwann cells compared with the empty fibrin conduit. Differentiated adipose-derived stem cells also enhanced regeneration distance in a similar manner to differentiated bone marrow mesenchymal stem cells. These observations suggest that adipose-derived stem cells may provide an effective cell population, without the limitations of the donor-site morbidity associated with isolation of Schwann cells, and could be a clinically translatable route towards new methods to enhance peripheral nerve repair.

  • 38.
    El-Habta, Roine
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Andersson, Gustav
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Kingham, Paul J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Backman, Ludvig J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    Anti-apoptotic effect of adipose tissue-derived stromal vascular fraction in denervated rat muscle2021Ingår i: Stem Cell Research & Therapy, E-ISSN 1757-6512, Vol. 12, nr 1, artikel-id 162Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Recovery of muscle function after peripheral nerve injury is often poor, and this can be attributed to muscle fiber atrophy and cell death. In the current study, we have investigated the effects of stromal vascular fraction (SVF) on muscle cell apoptosis and its potential to preserve muscle tissue following denervation.

    Methods: Rat gastrocnemius muscle was denervated by sciatic nerve transection. At 2 and 4 weeks after injury, muscles were examined histologically and apoptosis was measured using TUNEL assay and PCR array for a range of apoptotic genes. Additionally, an in vitro TNF-α apoptosis model was established using SVF cells co-cultured indirectly with primary rat myoblasts. Annexin V and TUNEL were used together with Western blotting to investigate the signaling pathways.

    Results: Denervated muscles showed significantly higher TUNEL reactivity at 2 and 4 weeks following nerve injury, and an increased expression of caspase family genes, mitochondria-related apoptotic genes, and tumor necrosis factor family genes. In cultured rat primary myoblasts, Annexin V labeling was significantly increased at 12 h after TNF-α treatment, and this was followed by a significant increase in TUNEL reactivity at 48 h. Western blotting showed that caspase-7 was activated/cleaved as well as the downstream substrate, poly (ADP-ribose) polymerase (PARP). Co-culture of myoblasts with SVF significantly reduced all these measures of apoptosis. Bax and Bcl-2 levels were not changed suggesting that the TNF-α-induced apoptosis occurred via mitochondria-independent pathways. The protective effect of SVF was also shown in vivo; injections of SVF cells into denervated muscle significantly improved the mean fiber area and diameter, as well as reduced the levels of TUNEL reactivity.

    Conclusions: This study provides new insights into how adipose tissue-derived cells might provide therapeutic benefits by preserving muscle tissue.

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  • 39.
    Englezou, Pavlos C.
    et al.
    University of Manchester.
    Degli Esposti, Mauro
    University of Manchester.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Reid, Adam J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. University of Manchester.
    Terenghi, Giorgio
    University of Manchester.
    Mitochondrial involvement in sensory neuronal cell death and survival2012Ingår i: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 221, nr 4, s. 357-367Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Peripheral nerve injuries (PNI) are continuing to be an ever-growing socio-economic burden affecting mainly the young working population and the current clinical treatments to PNI provide a poor clinical outcome involving significant loss of sensation. Thus, our understanding of the underlying factors responsible for the extensive loss of the sensory cutaneous subpopulation in the dorsal root ganglia (DRG) that occurs following injury needs to be improved. The current investigations focus in identifying visual cues of mitochondria-related apoptotic events in the various subpopulations of sensory cutaneous neurons. Sensory neuronal subpopulations were identified using FastBlue retrograde labelling following axotomy. Specialised fluorogenic probes, MitoTracker Red and MitoTracker Orange, were employed to visualise the dynamic changes of the mitochondrial population of neurons. The results reveal a fragmented mitochondrial network in sural neurons following apoptosis, whereas a fused elongated mitochondrial population is present in sensory proprioceptive muscle neurons following tibial axotomy. We also demonstrate the neuroprotective properties of NAC and ALCAR therapy in vitro. The dynamic mitochondrial network breaks down following oxidative exposure to hydrogen peroxide (H2O2), but reinitiates fusion after NAC and ALCAR therapy. In conclusion, this study provides both qualitative and quantitative evidence of the susceptibility of sensory cutaneous sub-population in apoptosis and of the neuroprotective effects of NAC and ALCAR treatment on H2O2-challenged neurons.

  • 40.
    Forsgren, Sture
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Andersson, Gustav
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Further proof of the existence of a non-neuronal cholinergic system in the human Achilles tendon: Presence of the AChR alpha 7 receptor in tendon cells and cells in the peritendinous tissue2015Ingår i: International Immunopharmacology, ISSN 1567-5769, E-ISSN 1878-1705, Vol. 29, nr 1, s. 195-200Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human tendon cells have the capacity for acetylcholine (ACh) production. It is not known if the tendon cells also have the potential for ACh breakdown, nor if they show expression of the nicotinic acetylcholine receptor AChR alpha 7 (alpha 7nAChR). Therefore, tendon tissue specimens from patients with midportion Achilles tendinopathy/tendinosis and from normal midportion Achilles tendons were examined. Reaction for the degradative enzyme acetylcholinesterase (AChE) was found in some tenocytes in only a few tendinopathy tendons, and was never found in those of control tendons. Tenocytes displayed more regularly alpha 7nAChR immunoreactivity. However, there was a marked heterogeneity in the degree of this reaction within and between the specimens. alpha 7nAChR immunoreactivity was especially pronounced for tenocytes showing an oval/widened appearance. There was a tendency that the magnitude of alpha 7nAChR immunoreactivity was higher in tendinopathy tendons as compared to control tendons. A stronger alpha 7nAChR immunoreactivity than seen for tenocytes was observed for the cells in the peritendinous tissue. It is likely that the alpha 7nAChR may be an important part of an auto-and paracrine loop of non-neuronal ACh that is released from the tendon cells. The effects may be related to proliferative and blood vessel regulatory functions as well as features related to collagen deposition. ACh can furthermore be of importance in leading to anti-inflammatory effects in the peritendinous tissue, a tissue nowadays considered to be of great relevance for the tendinopathy process. Overall, the findings show that tendon tissue, a tissue known to be devoid of cholinergic innervation, is a tissue in which there is a marked non-neuronal cholinergic system.

  • 41.
    Frestadius, Johnny
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Long term follow-up after interposition arthroplasty of the carpometacarpale 1-joint ad modum Hulin2015Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 42.
    Gassama, Samboujang
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Ultraljudsbaserad analys av senor i handen2020Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 43.
    Grip, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Källströmer, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Validity and reliability of wearable motion sensors for clinical assessment of shoulder function in brachial plexus birth injury2022Ingår i: Sensors, E-ISSN 1424-8220, Vol. 22, nr 23, artikel-id 9557Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The modified Mallet scale (MMS) is commonly used to grade shoulder function in brachial plexus birth injury (BPBI) but has limited sensitivity and cannot grade scapulothoracic and glenohumeral mobility. This study aims to evaluate if the addition of a wearable inertial movement unit (IMU) system could improve clinical assessment based on MMS. The system validity was analyzed with simultaneous measurements with the IMU system and an optical camera system in three asymptomatic individuals. Test–retest and interrater reliability were analyzed in nine asymptomatic individuals and six BPBI patients. IMUs were placed on the upper arm, forearm, scapula, and thorax. Peak angles, range of motion, and average joint angular speed in the shoulder, scapulothoracic, glenohumeral, and elbow joints were analyzed during mobility assessments and MMS tasks. In the validity tests, clusters of reflective markers were placed on the sensors. The validity was high with an error standard deviation below 3.6°. Intraclass correlation coefficients showed that 90.3% of the 69 outcome scores showed good-to-excellent test–retest reliability, and 41% of the scores gave significant differences between BPBI patients and controls with good-to-excellent test–retest reliability. The interrater reliability was moderate to excellent, implying that standardization is important if the patient is followed-up longitudinally.

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  • 44.
    Hart, Andrew M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Blond-McIndoe Research Laboratories, The University of Manchester, Stopford Building, Room 3.106, Oxford; Canniesburn Plastic Surgery Unit, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, UK.
    Terenghi, Giorgio
    Frozen-section fluorescence microscopy and stereology in the quanti cation of neuronal death within dorsal root ganglia2004Ingår i: Journal of Molecular Histology, ISSN 1567-2379, E-ISSN 1567-2387, Vol. 35, nr 6, s. 565-580Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Histochemical and morphological research increasingly relies upon quanti cation of complex biological systems. For such investigations to be meaningful, quanti cation techniques must meet the seemingly conflicting requirements of being theoretically robust, yet sufficiently practical to facilitate widespread applicability. Validity ought to be enhanced by theoretical simplicity, use of measured rather than assumed variables, and minimising observer interpretation. Practicality is facilitated by simplifying and reducing measurements, broadening applicability, and reducing costs and analysis time. As a result, quanti cation systems that rely upon sampling and estimation have been favoured over serial reconstruction techniques. To provide reliable estimates, sampling must be valid at all levels from tissue harvest, to the selection of microscope fields in which quanti cation is performed by techniques that account for the anisotropic distribution, and variable size of many elements in biological systems. These principles are embodied in the development of a stereological approach to the quanti cation of neuronal death within dorsal root ganglia after peripheral nerve injury. This frozen section technique is efficient and flexible, since it permits simultaneous morphological examination, TUNEL, or standard fluorescence immunohistochemistry, broadening its applicability. Section shrinkage is minimal, and counting by optical disection has proved to be time-efficient and sufficiently reproducible to reliably detect losses in the order of 5%, with minimal inter-observer variation. As is discussed, stereology has not yet met with universal acceptance, but by balancing theoretical validity with practical applicability, it has proved an excellent approach to the investigation of neuronal death within dorsal root ganglia.

  • 45. Hart, Andrew M
    et al.
    Terenghi, Giorgio
    Wiberg, Mikael
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi. Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Handkirurgi.
    Neuronal death after peripheral nerve injury and experimental strategies for neuroprotection.2008Ingår i: Neurological Research, ISSN 0161-6412, E-ISSN 1743-1328, Vol. 30, nr 10, s. 999-1011Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Despite considerable microsurgical innovation in peripheral nerve repair, the outcome has improved little since the 1940s, reflecting surgical inability to adequately address the complex neurobiology of nerve injury and regeneration. Axotomy-induced neuronal death is potentially the most fundamental problem, and given recently published data, a review is timely. METHODS: Initial review of relevant doctoral theses from the University of Umeå, and Blond-McIndoe Research Laboratories, the University of Manchester, plus initial PubMed search including terms 'neuron death' and 'neuroprotection', subsequently expanded to relevant quoted articles. RESULTS: Various factors related to patient (principally age) and injury (Sunderland grade, proximity to cell body and mechanism) determine the extent of neuronal death, the mechanism of which is reviewed. A considerable proportion of sensory neurons (particularly small cutaneous afferents) die after distal injury and death is more widespread after proximal injury. Motor neurons are susceptible to post-ganglionic plexus and spinal root level injury. Root avulsion causes the greatest cell death. The time course of neuronal death is fortuitously slow and mainly occurs by a process akin to apoptosis. A therapeutic window therefore exists, as do potential neuroprotective targets. Nerve repair is partly neuroprotective, but must be performed early. Exogenous neurotrophic factor administration (e.g. in tissue engineered conduits) is beneficial, but not practical for various reasons. In contrast, adjuvant neuroprotective pharmacotherapy is practical, and two clinically safe agents are reviewed. Acetyl-L-carnitine arrests sensory neuronal death and speeds up regeneration. N-acetyl-cysteine provides comparable sensory neuronal protection via mitochondrial preservation and protects motor neurons. Both agents are well characterized experimentally and highly effective even after clinically relevant delays between injury and treatment. Barriers to translational research are being addressed. DISCUSSION: The future of peripheral nerve repair lies in modulating neurobiology at the time of injury, repair and during regeneration. Neuroprotection may be an essential component of that therapeutic package.

  • 46.
    Hart, Andrew McKay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Blond-McIndoe Laboratories, Royal Free and University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London, UK.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Blond-McIndoe Laboratories, Royal Free and University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London, UK.
    Primary sensory neurons and satellite cells after peripheral axotomy in the adult rat: timecourse of cell death & elimination2002Ingår i: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 142, nr 3, s. 308-318Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The timecourse of cell death in adult dorsal root ganglia after peripheral axotomy has not been fully characterised. It is not clear whether neuronal death begins within I week of axotomy or continues beyond 2 months after axotomy. Similarly, neither the timecourse of satellite cell death in the adult, nor the effect of nerve repair has been described. L4 and L5 dorsal root ganglia were harvested at 1-14 days, 1-6 months after sciatic nerve division in the adult rat, in accordance with the Animals (Scientific Procedures) Act 1986. In separate groups the nerve was repaired either immediately or following a 1-week delay, and the ganglia were harvested 2 weeks after the initial transection. Microwave permeabilisation and triple staining enabled combined TUNEL staining, morphological examination and neuron counting by the stereological optical dissector technique. TUNEL-positive neurons, exhibiting a range of morphologies, were seen at all timepoints (peak 25 cells/group 2 weeks after axotomy) in axotomised ganglia only. TUNEL-positive satellite cell numbers peaked 2 months after axotomy and were more numerous in axotomised than control ganglia. L4 control ganglia contained 13,983 (SD 568) neurons and L5, 16,285 (SD 1,313). Neuron loss was greater in L5 than L4 axotomised ganglia, began at I week (15%, P=0.045) post-axotomy, reached 35% at 2 months (P<0.001) and was not significantly greater at 4 months or 6 months. Volume of axotomised ganglia fell to 19% of control by 6 months (P<0.001). In animals that underwent nerve repair, both the number of TUNEL-positive neurons and neuron loss were reduced. Immediate repair was more protective than repair after a 1-week delay. Thus TUNEL positivity precedes actual neuron loss, reflecting the time taken to complete cell death and elimination. Neuronal death begins within I day of peripheral axotomy, the majority occurs within the first 2 months, and limited death is still occurring at 6 months. Neuronal death is modulated by peripheral nerve repair and by its timing after axotomy. Secondary satellite cell death also occurs, peaking 2 months after axotomy. These results provide a logical framework for future research into neuronal and satellite cell death within the dorsal root ganglia and provide further insight into the process of axotomy induced neuronal death.

  • 47.
    Hart, Andrew McKay
    et al.
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Kellerth, Jan-Olof
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Wiberg, Mikael
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi. Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Handkirurgi.
    Sensory neuroprotection, mitochondrial preservation, and therapeutic potential of N-acetyl-cysteine after nerve injury.2004Ingår i: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 125, nr 1, s. 91-101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neuronal death is a major factor in many neuropathologies, particularly traumatic, and yet no neuroprotective therapies are currently available clinically, although antioxidants and mitochondrial protection appear to be fruitful avenues of research. The simplest system involving neuronal death is that of the dorsal root ganglion after peripheral nerve trauma, where the loss of approximately 40% of primary sensory neurons is a major factor in the overwhelmingly poor clinical outcome of the several million nerve injuries that occur each year worldwide. N-acetyl-cysteine (NAC) is a glutathione substrate which is neuroprotective in a variety of in vitro models of neuronal death, and which may enhance mitochondrial protection. Using TdT uptake nick-end labelling (TUNEL), optical disection, and morphological studies, the effect of systemic NAC treatment upon L4 and 5 primary sensory neuronal death after sciatic nerve transection was investigated. NAC (150 mg/kg/day) almost totally eliminated the extensive neuronal loss found in controls both 2 weeks (no treatment 21% loss, NAC 3%, P=0.03) and 2 months after axotomy (no treatment 35% loss, NAC 3%, P=0.002). Glial cell death was reduced (mean number TUNEL positive cells 2 months after axotomy: no treatment 51/ganglion pair, NAC 16/ganglion pair), and mitochondrial architecture was preserved. The effects were less profound when a lower dose was examined (30 mg/kg/day), although significant neuroprotection still occurred. This provides evidence of the importance of mitochondrial dysregulation in axotomy-induced neuronal death in the peripheral nervous system, and suggests that NAC merits investigation in CNS trauma. NAC is already in widespread clinical use for applications outside the nervous system; it therefore has immediate clinical potential in the prevention of primary sensory neuronal death, and has therapeutic potential in other neuropathological systems.

  • 48.
    Hart, Andrew McKay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Blond–McIndoe Centre, Royal Free and University College Medical School, London, UK.
    Exogenous leukaemia inhibitory factor enhances nerve regeneration after late secondary repair using a bioartificial nerve conduit2003Ingår i: British Journal of Plastic Surgery, ISSN 0007-1226, E-ISSN 1465-3087, Vol. 56, nr 5, s. 444-450Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The clinical outcome of peripheral nerve injuries remains disappointing, even in the ideal situation of a primary repair performed with optimal microsurgical techniques. Primary repair is appropriate for only about 85% of injuries, and outcome is worse following secondarynerverepair, partly owing to the reduced regenerative potential of chronically axotomised neurons. Leukaemiainhibitoryfactor (LIF) is a gp-130 neurocytokine that is thought to act as an ‘injury factor’, triggering the early-injury phenotype within neurons and potentially boosting their regenerative potential aftersecondarynerverepair. At 2–4 months after sciatic nerve axotomy in the rat, 1 cm gaps were repaired using either nerve isografts or poly-3-hydroxybutyrate conduits containing a calcium alginate and fibronectin hydrogel.

    Regeneration was determined by quantitative immunohistochemistry 6 weeks afterrepair, and the effect of incorporating recombinant LIF (100 ng/ml) into the conduits was assessed. LIF increased the regeneration distance in repairs performed after both 2 months (69%, P=0.019) and 4 months (123%, P=0.021), and was statistically comparable to nerve graft. The total area of axonal immunostaining increased by 21% (P>0.05) and 63% (P>0.05), respectively. Percentage immunostaining area was not increased in the 2 months group, but increased by 93% in the repairs performed 4 months after axotomy. Exogenous LIF, therefore, has a potential role in promoting peripheral nerveregenerationaftersecondaryrepair, and can be effectively delivered within poly-3-hydroxybutyrate bioartificialconduits used for nerverepair.

  • 49.
    Hart, Andrew McKay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Blond-McIndoe Centre, Royal Free and University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pharmacological enhancement of peripheral nerve regeneration in the rat by systemic acetyl-L-carnitine treatment2002Ingår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 334, nr 3, s. 181-185Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Peripheral nerve trauma remains a major cause of morbidity, largely due to the death of similar to40% of innervating sensory neurons, and to slow regeneration after repair. Acetyl-L-carnitine (ALCAR) is a physiological peptide that virtually eliminates sensory neuronal death, and may improve regeneration after primary nerve repair. This study determines the effect of ALCAR upon regeneration after secondary nerve repair, thereby isolating its effect upon neuronal regenerative capacity. Two months after unilateral sciatic nerve division 1 cm nerve graft repairs were performed (n = 5), and treatment with 50 mg/kg/day ALCAR was commenced for 6 weeks until harvest. Regeneration area and distance were determined by quantitative immunohistochemistry. ALCAR treatment significant increased immunostaining for both nerve fibres (total area 264% increase, P < 0.001; percentage area 229% increase, P < 0.001), and Schwann cells (total area 264% increase, P < 0.05; percentage area 86% increase, P < 0.05), when compared to no treatment. Regeneration into the distal stump was greatly enhanced (total area 2242% increase, P = 0.008; percentage area 3034% increase, P = 0.008). ALCAR significantly enhances the regenerative capacity of neurons that survive peripheral nerve trauma, in addition to its known neuroprotective effects.

  • 50.
    Hart, Andrew McKay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Blond-McIndoe Centre, Royal Free & University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Youle, Mike
    Royal Free Centre for HIV Medicine, Royal Free Hospital, London, UK.
    Terenghi, Giorgio
    Blond-McIndoe Centre, Royal Free & University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK.
    Systemic acetyl-L-carnitine eliminates sensory neuronal loss after peripheral axotomy: a new clinical approach in the management of peripheral nerve trauma2002Ingår i: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 145, nr 2, s. 182-189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several hundred thousand peripheral nerve injuries occur each year in Europe alone. Largely due to the death of around 40% of primary sensory neurons, sensory outcome remains disappointingly poor despite considerable advances in surgical technique; yet no clinical therapies currently exist to prevent this neuronal death. Acetyl-L-carnitine (ALCAR) is a physiological peptide with roles in mitochondrial bioenergetic function, which may also increase binding of nerve growth factor by sensory neurons. Following unilateral sciatic nerve transection, adult rats received either one of two doses of ALCAR or sham, or no treatment. Either 2 weeks or 2 months later, L4 and L5 dorsal root ganglia were harvested bilaterally, in accordance with the Animal (Scientific Procedures) Act 1986. Neuronal death was quantified with a combination of TUNEL [TdT (terminal deoxyribonucleotidyl transferase) uptake nick end labelling] and neuron counts obtained using the optical disector technique. Sham treatment had no effect upon neuronal death. ALCAR treatment caused a large reduction in the number of TUNEL-positive neurons 2 weeks after axotomy (sham treatment 33/group; low-dose ALCAR 6/group, P=0.132; high-dose ALCAR 3/group, P<0.05), and almost eliminated neuron loss (sham treatment 21%; low-dose ALCAR 0%, P=0.007; high-dose ALCAR 2%, P<0.013). Two months after axotomy the neuroprotective effect of high-dose ALCAR treatment was preserved for both TUNEL counts (no treatment five/group; high-dose ALCAR one/group) and neuron loss (no treatment 35%; high-dose ALCAR -4%, P<0.001). These results provide further evidence for the role of mitochondrial bioenergetic dysfunction in post-traumatic sensory neuronal death, and also suggest that acetyl-L-carnitine may be the first agent suitable for clinical use in the prevention of neuronal death after peripheral nerve trauma.

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