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Alfredson, Håkan
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Welford, P. & Alfredson, H. (2018). Achilles insertion bone pathology not related to pain in a triathlete with cystic fibrosis. Journal of Surgical Case Reports (8), Article ID rjy182.
Open this publication in new window or tab >>Achilles insertion bone pathology not related to pain in a triathlete with cystic fibrosis
2018 (English)In: Journal of Surgical Case Reports, ISSN 2042-8812, E-ISSN 2042-8812, no 8, article id rjy182Article in journal (Refereed) Published
Abstract [en]

This report concerns the unusual case of a 48-year old, world-class triathlete who has won 11 ironman competitions. She has reached the top level of international endurance sport in spite of being diagnosed with cystic fibrosis. This patient presented with Achilles pain and severe bony pathology at her left Achilles insertion. Traditionally this condition is treated via tendon detachment and re-attachment or intra-tendinous surgery, followed by a protracted rehabilitation. These procedures were considered risky due to this patient's chronic disease with vulnerability to immobilization. Instead, she was treated by surgical removal of the superficial bursa alone, under local anaesthetic. This allowed the patient to become active and load her Achilles tendon immediately, and resulted in a significant symptomatic improvement. This case illustrates that despite the presence of severe tendon and bone pathology at the Achilles insertion, pain may originate in the superficial bursa; a structure ignored by traditional operations.

Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Orthopaedics Surgery
Identifiers
urn:nbn:se:umu:diva-152228 (URN)10.1093/jscr/rjy182 (DOI)000443544800002 ()30151099 (PubMedID)
Available from: 2018-10-25 Created: 2018-10-25 Last updated: 2018-10-25Bibliographically approved
Gaida, J. E., Alfredson, H., Scott, A., Mousavizadeh, R. & Forsgren, S. (2018). Apolipoprotein A1 distribution pattern in the human Achilles tendon. Scandinavian Journal of Medicine and Science in Sports, 28(5), 1506-1513
Open this publication in new window or tab >>Apolipoprotein A1 distribution pattern in the human Achilles tendon
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2018 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 28, no 5, p. 1506-1513Article in journal (Refereed) Published
Abstract [en]

Metabolic factors such as cholesterol appear to play an important role in the development of Achilles tendinopathy. There is, however, no morphologic proof explaining the link between high cholesterol and tendinopathy. As apolipoprotein A1 (Apo-A1) is essential for reverse cholesterol transport, it may be related to cholesterol overload in tendon. Nothing is known about Apo-A1 expression in tendon tissue. We examined the distribution of Apo-A1 protein in biopsies from normal and tendinopathy-affected human Achilles tendons, and APOA1 mRNA production from cultured human hamstring tenocytes. Specific immunoreactions for Apo-A1 were detected. The tenocytes showed specific Apo-A1 immunoreactions. These reactions were usually distinct in the tendinopathy specimens. While the tendinopathy specimens often showed granular/small deposit reactions, the slender tenocytes of control specimens did not show this pattern. The magnitude of Apo-A1 immunoreactivity was especially marked in the tendinopathy specimens, as there is a high number of tenocytes. Reactions were also seen in the walls of blood vessels located within the tendon tissue proper of both the normal and tendinopathy tendons and within the peritendinous/fatty tissue of the tendinopathy tendons. The reactions were predominantly in the form of deposit reactions within the smooth muscle layer of the vessel walls. Cultured hamstring tenocytes produced APOA1 mRNA. We demonstrated the presence of Apo-A1 in human tendon tissue. This suggests there may be a link between Achilles tendinopathy and cholesterol metabolism. We hypothesize that Apo-A1 may be important for tenocyte and blood vessel function within tendons.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
Apo-A1, HDL-C, immunohistochemistry, reverse cholesterol transport, tendinopathy, tendon
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:umu:diva-150705 (URN)10.1111/sms.13051 (DOI)000430471900003 ()29315811 (PubMedID)2-s2.0-85041679099 (Scopus ID)
Available from: 2018-09-05 Created: 2018-09-05 Last updated: 2018-09-05Bibliographically approved
Smith, J., Alfredson, H., Masci, L., Sellon, J. L. & Woods, C. D. (2017). Differential Plantaris-Achilles Tendon Motion: A Sonographic and Cadaveric Investigation. PM&R, 9(7), 691-698
Open this publication in new window or tab >>Differential Plantaris-Achilles Tendon Motion: A Sonographic and Cadaveric Investigation
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2017 (English)In: PM&R, ISSN 1934-1482, E-ISSN 1934-1563, Vol. 9, no 7, p. 691-698Article in journal (Refereed) Published
Abstract [en]

Background: Differential motion between the plantaris and Achilles tendons has been hypothesized to contribute to pain in some patients presenting with Achilles tendinopathy. However, objective evidence of differential Achilles-plantaris motion is currently lacking from the literature. Objective: To determine whether differential, multidirectional motion exists between the plantaris tendon (PT) and Achilles tendon (AT) as documented by dynamic ultrasound (US) and postdissection examination in an unembalmed cadaveric model. Design: Prospective, cadaveric laboratory investigation. Setting: Procedural skills laboratory in a tertiary medical center. Subjects: Twenty unembalmed knee-ankle-foot specimens (9 right, 11 left) obtained from 6 male and 10 female donors ages 55-96 years (mean 80 years) with body mass indices of 14.1-33.2 kg/m(2) (mean 22.5 kg/m(2)). Methods: A single, experienced operator used high -resolution dynamic US to qualitatively document differential PT-AT motion during passive ankle dorsifiexion-plantarflexion. Specimens were then dissected and passive dorsiflexion-plantarfiexion was repeated while differential PT-AT motion was visualized directly. Main Outcome Measurements: Presence or absence of multidirectional differential PT-AT motion. Results: All 20 specimens exhibited smooth but variable amplitude multidirectional differential PT-AT motion. Whereas US readily demonstrated medial-lateral and anterior-posterior PT motion relative to the AT, differential longitudinal motion was only appreciated on dissection and direct inspection. Many specimens exhibited partial or complete encasement of the PT between the gastrocnemius portion of the AT and the soleus aponeurosis. Conclusion: Some degree of multidirectional differential PT-AT motion appears to be a normal phenomenon, and PT motion can be evaluated sonographically in both the medial -lateral and anterior-posterior directions. The existence of normal differential PT-AT motion suggests that alterations in PT motion or repetitive stress within the PT-AT interval may produce symptoms in some patients presenting with Achilles region pain syndromes. The PT should be evaluated in all patients presenting with Achilles, plantaris, or calf pain syndromes. Future research would benefit from the development of a sonographic classification system for PT anatomy and motion with the goal of differentiating normal versus pathologic states and identifying risk factors for symptom development.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2017
National Category
Orthopaedics Physiotherapy
Identifiers
urn:nbn:se:umu:diva-138606 (URN)10.1016/j.pmrj.2016.10.013 (DOI)000406575300007 ()27789336 (PubMedID)
Available from: 2017-09-08 Created: 2017-09-08 Last updated: 2018-06-09Bibliographically approved
Spang, C., Renström, L., Alfredson, H. & Forsgren, S. (2017). Marked expression of TNF receptors in human peritendinous tissues including in nerve fascicles with axonal damage: Studies on tendinopathy and tennis elbow. Journal of Musculoskeletal and Neuronal Interactions - JMNI, 17(3), 226-236
Open this publication in new window or tab >>Marked expression of TNF receptors in human peritendinous tissues including in nerve fascicles with axonal damage: Studies on tendinopathy and tennis elbow
2017 (English)In: Journal of Musculoskeletal and Neuronal Interactions - JMNI, ISSN 1108-7161, Vol. 17, no 3, p. 226-236Article in journal (Refereed) Published
Abstract [en]

Background: The peritendinous connective tissues can have importance in chronic tendon pain. Recently cytokine TNF-alpha has been suggested to be involved in tendinopathic processes. It is not known how TNF-alpha and its receptors TNFR1 and TNFR2 are expressed in peritendinous tissues.

Methods: The objective for this study was to immunohistochemically evaluate the expression patterns of these in the peritendinous tissue located between the plantaris and Achilles tendons and the one located superficially to the extensor origin at the elbow region for patients with tendinopathy/tennis elbow.

Results: The nerve fascicles were of two types, one type being homogenously stained for the nerve markers beta III-tubulin and neurofilament and the other showing deficits for these suggesting features of axonal damage. Much more distinct TNFR1/TNFR2 immunoreactions were seen for the latter nerve fascicles. TNFR1 was seen in axons, TNFR2 mainly in Schwann cells. TNFR1 and particularly TNFR2 were seen in walls of parts of blood vessels. The dispersed cells showed frequently TNFR1 and TNFR2 immunoreactivity.

Discussion: These findings suggest that TNF-alpha can be related to degenerative events but also attempts for healing concerning the nerve structures. The marked expression of the TNF-alpha system in the peritendinous tissue suggests an impact of TNF-alpha in tendinopathy/tennis elbow.

Place, publisher, year, edition, pages
JMNI, 2017
Keywords
TNF, Peritendinous, Tendinopathy, Tennis Elbow, Nerve Degeneration
National Category
Neurosciences Physiology
Identifiers
urn:nbn:se:umu:diva-140056 (URN)000410545600012 ()28860425 (PubMedID)
Available from: 2017-10-04 Created: 2017-10-04 Last updated: 2018-06-09Bibliographically approved
Andersson, G., Backman, L. J., Christensen, J. & Alfredson, H. (2017). Nerve distributions in insertional Achilles tendinopathy - a comparison of bone, bursae and tendon. Histology and Histopathology, 32(3), 263-270
Open this publication in new window or tab >>Nerve distributions in insertional Achilles tendinopathy - a comparison of bone, bursae and tendon
2017 (English)In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 32, no 3, p. 263-270Article in journal (Refereed) Published
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.

Keywords
Insertional Achilles tendinopathy, Innervation, Subcutaneous bursa, Retrocalcaneal bursa
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-130214 (URN)10.14670/HH-11-790 (DOI)000390220000006 ()
Available from: 2017-02-02 Created: 2017-01-14 Last updated: 2018-06-09Bibliographically approved
Alfredson, H. (2017). Persistent pain in the Achilles midportion?: Consider the plantaris tendon as a possible culprit!. British Journal of Sports Medicine, 51(10), 833-834
Open this publication in new window or tab >>Persistent pain in the Achilles midportion?: Consider the plantaris tendon as a possible culprit!
2017 (English)In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 51, no 10, p. 833-834Article, review/survey (Refereed) Published
Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2017
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:umu:diva-136197 (URN)10.1136/bjsports-2016-097360 (DOI)000400583100018 ()28235758 (PubMedID)
Available from: 2017-07-06 Created: 2017-07-06 Last updated: 2018-06-09Bibliographically approved
Spang, C. & Alfredson, H. (2017). Richly innervated soft tissues covering the superficial aspect of the extensor origin in patients with chronic painful tennis elbow - Implication for treatment?. Journal of Musculoskeletal and Neuronal Interactions - JMNI, 17(2), 97-103
Open this publication in new window or tab >>Richly innervated soft tissues covering the superficial aspect of the extensor origin in patients with chronic painful tennis elbow - Implication for treatment?
2017 (English)In: Journal of Musculoskeletal and Neuronal Interactions - JMNI, ISSN 1108-7161, Vol. 17, no 2, p. 97-103Article in journal (Refereed) Published
Abstract [en]

Background: Tennis elbow is difficult to treat. The results of surgical treatments are not convincing. Treatment studies on Achilles and patellar tendinopathy targeting the richly innervated and vascularized soft tissues outside the tendon have shown promising outcomes. The innervation patterns in the fibrous/fatty tissues superficially to the elbow extensor origin have not been clarified.

Methods: Nine tissue specimens from the fibrous/fatty tissue covering the extensor origin was taken from seven patients (mean age: 45 years) undergoing surgical treatment for chronic painful tennis elbow. The specimens were stained for morphology (haematoxylin & eosin, H&E) and immunohistochemically for general nerve marker protein gene product 9.5 (PGP 9.5) and markers for sympathetic (tyrosine hydroxylase, TH) and sensory nerve fibres (calcitonin gene-related peptide, CGRP).

Results: All specimens contained multiple blood vessels and nerve structures indicated by morphology and immunoreactions. There was a frequent occurrence of TH reactions, especially peri-vascularly, but also in nerve fascicles. Immunoreactions for CGRP were seen in nerve fascicles and isolated nerve fibres.

Conclusion: The results provide new information on the innervation patterns of the superficial tissues of the extensor origin and their potential as source of tennis elbow pain. Level of Evidence: IV.

Keywords
Innervation, Tennis Elbow, Lateral Epicondylitis, Superficial, Soft Tissue
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:umu:diva-138047 (URN)000405504200011 ()28574416 (PubMedID)
Available from: 2017-08-11 Created: 2017-08-11 Last updated: 2018-06-09Bibliographically approved
Fong, G., Backman, L. J., Alfredson, H., Scott, A. & Danielson, P. (2017). The Effects of Substance P and Acetylcholine on Human Tenocyte Proliferation Converge Mechanistically via TGF-β1. PLoS ONE, 12(3), Article ID e0174101.
Open this publication in new window or tab >>The Effects of Substance P and Acetylcholine on Human Tenocyte Proliferation Converge Mechanistically via TGF-β1
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174101Article in journal (Refereed) Published
Abstract [en]

Previous in vitro studies on human tendon cells (tenocytes) have demonstrated that the exogenous administration of substance P (SP) and acetylcholine (ACh) independently result in tenocyte proliferation, which is a prominent feature of tendinosis. Interestingly, the possible link between SP and ACh has not yet been explored in human tenocytes. Recent studies in other cell types demonstrate that both SP and ACh independently upregulate TGF-β1 expression via their respective receptors, the neurokinin 1 receptor (NK-1R) and muscarinic ACh receptors (mAChRs). Furthermore, TGF-β1 has been shown to downregulate NK-1R expression in human keratocytes. The aim of this study was to examine if TGF-β1 is the intermediary player involved in mediating the proliferative pathway shared by SP and ACh in human tenocytes. The results showed that exogenous administration of SP and ACh both caused significant upregulation of TGF-β1 at the mRNA and protein levels. Exposing cells to TGF-β1 resulted in increased cell viability of tenocytes, which was blocked in the presence of the TGFβRI/II kinase inhibitor. In addition, the proliferative effects of SP and ACh on tenocytes were reduced by the TGFβRI/II kinase inhibitor; this supports the hypothesis that the proliferative effects of these signal substances are mediated via the TGF-β axis. Furthermore, exogenous TGF-β1 downregulated NK-1R and mAChRs expression at both the mRNA and protein levels, and these effects were negated by simultaneous exposure to the TGFβRI/II kinase inhibitor, suggesting a negative feedback loop. In conclusion, the results indicate that TGF-β1 is the intermediary player through which the proliferative actions of both SP and ACh converge mechanistically.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-131396 (URN)10.1371/journal.pone.0174101 (DOI)000396318300126 ()
Note

Originally published in manuscript form

Available from: 2017-02-13 Created: 2017-02-13 Last updated: 2018-06-09Bibliographically approved
Gaida, J. E., Alfredson, H., Forsgren, S. & Cook, J. L. (2016). A pilot study on biomarkers for tendinopathy: lower levels of serum TNF-alpha and other cytokines in females but not males with Achilles tendinopathy. BMC Sports Science Medicine and Rehabilitation, 8, Article ID 5.
Open this publication in new window or tab >>A pilot study on biomarkers for tendinopathy: lower levels of serum TNF-alpha and other cytokines in females but not males with Achilles tendinopathy
2016 (English)In: BMC Sports Science Medicine and Rehabilitation, ISSN 2052-1847, Vol. 8, article id 5Article in journal (Refereed) Published
Abstract [en]

Background: Achilles tendinopathy is a painful musculoskeletal condition that is common among athletes, and which limits training capacity and competitive performance. The lack of biomarkers for tendinopathy limits research into risk factors and also the evaluation of new treatments. Cytokines and growth factors involved in regulating the response of tendon cells to mechanical load have potential as biomarkers for tendinopathy. Methods: This case-control study compared serum concentration of cytokines and growth factors (TNF-alpha, IL-1 beta, bFGF, PDFG-BB, IFN-gamma, VEGF) between individuals with chronic Achilles tendinopathy and controls. These were measured in fasting serum from 22 individuals with chronic Achilles tendinopathy and 10 healthy controls. Results were analysed in relation to gender and physical activity pattern. Results: TNF-alpha concentration was lower in the entire tendinopathy group compared with the entire control group; none of the other cytokines were significantly different. TNF-alpha levels were nevertheless highly correlated with the other cytokines measured, in most of the subgroups. Analysed by gender, TNF-alpha and PDGF-BB concentrations were lower in the female tendinopathy group but not the male tendinopathy group. A trend was seen for lower IL-1 beta in the female tendinopathy group. Physical activity was correlated with TNF-alpha, PDGF-BB and IL-1 beta to varying extents for control subgroups, but not for the female tendinopathy group. No correlations were seen with BMI or duration of symptoms. Conclusions: This pilot study indicates a lower level of TNF-alpha and PDGF-BB, and to some extent IL-1 beta among females, but not males, in the chronic phase of Achilles tendinopathy. It is suggested that future studies on tendinopathy biomarkers analyse male and female data separately. The lack of correlation between cytokine level and physical activity in the female tendinopathy group warrants further study.

Keywords
Cytokines, Tumor necrosis factor alpha, Biomarkers, Musculoskeletal pain
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:umu:diva-129997 (URN)10.1186/s13102-016-0026-0 (DOI)000386701500001 ()26925234 (PubMedID)
Available from: 2017-01-12 Created: 2017-01-11 Last updated: 2018-06-09Bibliographically approved
Masci, L., Spang, C., van Schie, H. T. M. & Alfredson, H. (2016). How to diagnose plantaris tendon involvement in midportion Achilles tendinopathy: clinical and imaging findings. BMC Musculoskeletal Disorders, 17, Article ID 97.
Open this publication in new window or tab >>How to diagnose plantaris tendon involvement in midportion Achilles tendinopathy: clinical and imaging findings
2016 (English)In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, article id 97Article in journal (Refereed) Published
Abstract [en]

Background: The purpose of this investigation was to evaluate if clinical assessment, Ultrasound + Colour Doppler (US + CD) and Ultrasound Tissue Characterisation (UTC) can be useful in detecting plantaris tendon involvement in patients with midportion Achilles tendinopathy. Methods: Twenty-three tendons in 18 patients (14 men, mean age: 37 years and 4 women: 44 years) (5 patients with bilateral tendons) with midportion Achilles tendinopathy were surgically treated with a scraping procedure and plantaris tendon removal. For all tendons, clinical assessment, Ultrasound + Colour Doppler (US + CD) examination and Ultrasound Tissue Characterisation (UTC) were performed. Results: At surgery, all 23 cases had a plantaris tendon located close to the medial side of the Achilles tendon. There was vascularised fat tissue in the interface between the Achilles and plantaris tendons. Clinical assessment revealed localised medial activity-related pain in 20/23 tendons and focal medial tendon tenderness in 20/23 tendons. For US + CD, 20/23 tendons had a tendon-like structure interpreted to be the plantaris tendon and localised high blood flow in close relation to the medial side of the Achilles. For UTC, 19/23 tendons had disorganised (type 3 and 4) echopixels located only in the medial part of the Achilles tendon indicating possible plantaris tendon involvement. Conclusions: US + CD directly, and clinical assessment indirectly, can detect a close by located plantaris tendon in a high proportion of patients with midportion Achilles tendinopathy. UTC could complement US + CD and clinical assessment by demonstrating disorganised focal medial Achilles tendon structure indicative of possible plantaris involvement.

Place, publisher, year, edition, pages
BioMed Central, 2016
Keywords
Achilles tendinopathy, Plantaris tendon, Ultrasound Tissue Characterisation, Ultrasound, Medial pain
National Category
Orthopaedics Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-118244 (URN)10.1186/s12891-016-0955-5 (DOI)000370695000002 ()
Available from: 2016-03-18 Created: 2016-03-14 Last updated: 2018-06-07Bibliographically approved
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