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Abstract

endinopathy, a broad term used to describe disorders in and around tendons, 1,2 is associated with repetitive tensile forces exerted on tendons. 3-5 Rapid increases in the duration and intensity of these forces may cause tendon injuries, 6 possibly the starting point in the pathogenesis of chronic tendinopathy. The exact incidence of chronic tendinopathy is unknown given the vast population of professional and recreational athletes suffering from this condition at different anatomic sites. Studies on incidence of tendinopathies are usually site 7 or sport 8 specific, and only provide an approximation of the magnitude of the problem faced by musculoskeletal and sports medicine clinicians in treating this disorder. In addi- tion, a large number of sedentary subjects develop tendinopathy with no apparent history of increased physical activity. Disorganized, haphazard healing, with frayed, separated, and otherwise disrupted collagen fibrils, are features of tendinopathy. 3,9 These lesions are characterized by the absence of inflammatory cells and a poor healing response. 1,9 Age-related tendon changes, and not just mechanical overload, may thus play a role in the pathogenesis of tendinopathy, although the exact etiologic, pathophysiologic, and healing mechanisms are still unknown. 5,10 Gene expression studies have shown an absence of any inflammatory process in chronic Achilles tendinopathy. 11 Microdialysis experiments have shown no evidence of intratendinous chemical inflammation, with prostaglandin E2 (PGE2) levels being normal in chronic tendinopathies. 12 Microdialysis has also shown higher levels of glutamate, an excitatory neurotransmitter and a potent modulator of pain in the central nervous system, 13 in tendinopathic tendons compared with normal tendons. 12,14 The same technique reveals that the local concentration of lactate in the tendinopathic Achilles tendon is almost twice that of the normal Achilles tendon. 15 It is possible that there is an ischemic component in the pathogenesis of tendinopathy. Ischemia may precede the start of tendinopathy, but examination of tendinopathic lesions reveals neovascularization 16 and increased blood flow in the affected area of the tendon. 17 Neovascularization may be a response to a primary injury or may be the result of a metabolic disorder. It is possible that anaerobic conditions exist in areas of tendinopathy that have a poor blood supply, and are the primary cause of neovascularization. 15 Neovessels and their accompanying nerves, may be responsible for the pain in the tendinopathic tendon, 18 which would account for the success of local injection of sclerosants such as Polidocanol in the management tendinopathy. 18 Chronic tendinopathy may well be the final manifestation of a long-standing met- abolic process in which inflammation, although an initiator, does not participate in the final histopathologic and biochemical features of chronic tendinopathy. It is important in under- standing this hypothesis to recall the mechanism of tendon healing. A tendon heals by undergoing inflammatory (1-7 days of injury), proliferative (7-21 days), and remodeling (3 weeks-1 year) phases. 3,19 Despite collagen maturation and remodeling, tendons are biochemically and metabolically less active than bone and muscle. 3,19 Type III collagen synthesized by fibroblasts in the proliferative phase is gradually replaced by type I collagen from days 12 to 14, with a progressive increase in tensile strength. 3
EDITORIAL
Nonsteroidal Antiinflammatory Drugs
in Tendinopathy
Friend or Foe
Merzesh Magra, MRCS and Nicola Maffulli, PhD, FRCS (Orth)
Tendinopathy, a broad term used to describe disorders in and around tendons,
1,2
is
associated with repetitive tensile forces exerted on tendons.
3–5
Rapid increases in the
duration and intensity of these forces may cause tendon injuries,
6
possibly the starting point
in the pathogenesis of chronic tendinopathy. The exact incidence of chronic tendinopathy is
unknown given the vast population of professional and recreational athletes suffering from
this condition at different anatomic sites. Studies on incidence of tendinopathies are usually
site
7
or sport
8
specific, and only provide an approximation of the magnitude of the problem
faced by musculoskeletal and sports medicine clinicians in treating this disorder. In addi-
tion, a large number of sedentary subjects develop tendinopathy with no apparent history of
increased physical activity.
Disorganized, haphazard healing, with frayed, separated, and otherwise disrupted
collagen fibrils, are features of tendinopathy.
3,9
These lesions are characterized by the
absence of inflammatory cells and a poor healing response.
1,9
Age-related tendon changes,
and not just mechanical overload, may thus play a role in the pathogenesis of tendinopathy,
although the exact etiologic, pathophysiologic, and healing mechanisms are still
unknown.
5,10
Gene expression studies have shown an absence of any inflammatory process in
chronic Achilles tendinopathy.
11
Microdialysis experiments have shown no evidence
of intratendinous chemical inflammation, with prostaglandin E
2
(PGE
2
) levels being normal
in chronic tendinopathies.
12
Microdialysis has also shown higher levels of glutamate, an
excitatory neurotransmitter and a potent modulator of pain in the central nervous system,
13
in tendinopathic tendons compared with normal tendons.
12,14
The same technique reveals
that the local concentration of lactate in the tendinopathic Achilles tendon is almost twice
that of the normal Achilles tendon.
15
It is possible that there is an ischemic component in the pathogenesis of tendinopathy.
Ischemia may precede the start of tendinopathy, but examination of tendinopathic lesions
reveals neovascularization
16
and increased blood flow in the affected area of the tendon.
17
Neovascularization may be a response to a primary injury or may be the result of a metabolic
disorder. It is possible that anaerobic conditions exist in areas of tendinopathy that have a
poor blood supply, and are the primary cause of neovascularization.
15
Neovessels and their
accompanying nerves, may be responsible for the pain in the tendinopathic tendon,
18
which
would account for the success of local injection of sclerosants such as Polidocanol in the
management tendinopathy.
18
Chronic tendinopathy may well be the final manifestation of a long-standing met-
abolic process in which inflammation, although an initiator, does not participate in the final
histopathologic and biochemical features of chronic tendinopathy. It is important in under-
standing this hypothesis to recall the mechanism of tendon healing. A tendon heals by
undergoing inflammatory (1–7 days of injury), proliferative (7–21 days), and remodeling
(3 weeks–1 year) phases.
3,19
Despite collagen maturation and remodeling, tendons are
biochemically and metabolically less active than bone and muscle.
3,19
Type III collagen
synthesized by fibroblasts in the proliferative phase is gradually replaced by type I collagen
from days 12 to 14, with a progressive increase in tensile strength.
3
From the Department of Trauma and Orthopaedic Surgery, Keele University School of Medicine, Hartshill, United Kingdom.
Reprints: Nicola Maffulli, Department of Trauma and Orthopaedic Surgery, Keele University School of Medicine, Thornburrow Drive, Hartshill, ST4 7QB,
United Kingdom.
Copyright Ó2006 by Lippincott Williams & Wilkins
Clin J Sport Med Volume 16, Number 1, January 2006 1
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
In a rat Achilles tendinopathy model, different pop-
ulations of inflammatory cells, such as neutrophils and macro-
phages, accumulate immediately after injury,
20
followed by
a further macrophage accumulation 1 to 3 days after injury.
20
Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the
accumulation of inflammatory cells in the acute phase of in-
flammation, but neither prevent tissue damage nor accelerate
the overall healing process.
21
No studies have been performed to date on animal
models with chronic tendinopathy, but we could assume that
injury followed by an inflammatory reaction could start a chain
of events that ultimately leads to chronic tendinopathy, which,
at the point of clinical relevance, does not show inflammatory
features.
1,9
From our understanding of the etiology and devel-
opment of this condition, we believe that there is no scientific
basis to manage chronic tendinopathy with NSAIDs.
NSAIDS IN TENDINOPATHIES
NSAIDs inhibit tissue inflammation by repressing cyclo-
oxygenase (COX) activity, with a reduction in the synthesis of
proinflammatory prostaglandins.
22
Management of an anatomically defined medical
condition is ideally based on an understanding of its patho-
physiology. Although, as noted earlier, tendinopathy is a non-
inflammatory condition, NSAIDs are widely used in attempts
at treatment.
23–27
Ironically, the analgesic effect of NSAIDs
28
allows patients to ignore early symptoms, possibly imposing
further damage on the affected tendon and delaying definitive
healing. Topical Naproxen gel produced a marginal advantage
in relieving symptoms after 3 and 7 days in patients with acute
tendinopathies who had symptoms for less than 48 hours.
29
Although NSAIDs may provide some pain relief in such
patients, they do not actually result in sustained improvement
in the healing process.
2
It is still not known whether NSAIDs
actually change the natural history of tendinopathy or whether
they merely exert an analgesic action.
2
Recent studies on rats
with acute tendon injuries show that NSAID administration
does not prevent collagen degradation and loss of tensile force
in tendons.
21
It is therefore questionable whether NSAIDs should
be used to alleviate pain in so-called acute tendinopathy.
21
NSAIDs are not effective in athletes with tendinopathy.
23
Most studies of NSAID treatment of tendinopathy have a short
follow-up.
2
Double-blind, randomized, placebo-controlled clin-
ical trials of NSAIDs used in the management of tendinopathies
based on clinical symptoms and signs only have shown no ben-
eficial effects.
30
Even these placebo-controlled clinical studies
are difficult to interpret because of the inability to control for the
severity of the lesion, level of athletic participation, and other
variables.
NSAIDs could theoretically benefit patients with tendin-
opathy by increasing the tensile strength of tendons via accel-
erated formation of cross-linkages between collagen fibers.
23,28,31
In animal models, COX inhibitors do show a beneficial effect on
tendon regeneration after transection, in exactly this fashion.
32
However, these studies were conducted on rats with Achilles
tendons that had been surgically divided, a situation that does not
reflect the conditions encountered in chronic tendinopathy.
Another study using a rat model showed that, in the first few days
after Achilles tendon transection, the inflammatory response was
necessary for normal repair, and should not be inhibited.
33
Early
NSAID administration led to a reduction in the amount of force
and stress required for the tendon to fail.
33
During remodeling,
on the other hand, inflammation has a negative influence, and
NSAIDs such as COX-2 inhibitors might be valuable for the
final outcome.
33
Indeed, late treatment with COX-2 inhibitors
leads to increased tensile strength, although they do not change
the histopathologic picture.
33
COX-2 inhibitors should therefore
be avoided in the early period after tendon injury, given their
deleterious effect on tensile strength.
Although in vitro studies on human tendon fibroblasts
treated with NSAIDs have shown a decreased expression of
PGE
2
, they also show an increased expression of leukotriene B
4
(LTB
4
).
34
The reduction in PGE
2
may give patients some pain
relief; increased LTB
4
, however, could potentially exacerbate the
situation via increased neutrophilic infiltration and lymphocyte
activation,
35
paradoxically causing inflammatory and degener-
ative changes in the tendon. Thus, in tendinopathy, leukotriene
pathway activation occurs after cyclical strain on tendons, and
treatment with NSAIDs may actually worsen the condition.
34
CONCLUSION
Pharmacologic management strategies for tendinopa-
thies vary considerably, and are frequently based on empirical
evidence. Can the continued use of NSAIDs for the treatment
of tendinopathies be justified? The available literature would
suggest that in the absence of an overt inflammatory process,
there is no rational basis for the use of NSAIDs in chronic
tendinopathy, because they are unlikely to change its still ill-
defined natural history. Despite this reality, many clinicians
still anticipate a quicker and better recovery using these agents.
There is no biologic basis for NSAID effectiveness in treating
this condition, and no evidence of any benefit. NSAIDs appear
to be effective, to some extent, for pain control. This causes
patients to ignore early symptoms, and thus may lead to further
damage of the tendon and delay definitive healing. Early
NSAIDs administration after an injury may have a deleterious
effect on long-term tendon healing. It would thus seem
reasonable to shift our research efforts to other forms of con-
servative management. Examining strategies that promote the
migration and activation of tenocytes to influence tendon
healing and function might be an appropriate first step. It is
equally appropriate to limit our use of NSAIDs in the man-
agement of tendinopathy. What may appear clinically as an
‘acute tendinopathy’’ is actually a well-advanced failure of a
chronic healing response in which there is neither histologic
nor biochemical evidence of inflammation.
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... Currently, the treatment of tendinopathy involves the oral administration of NSAIDs, corticosteroid infiltrations, physical therapy (laser and/or ultrasound,) and shock waves (Extracorporeal Shock Wave Therapy). These therapies can have some limitations: 1) the available literature suggests that in absence of an ongoing inflammatory process, NSAIDs are not able to modify the course of chronic tendinopathy [2][3][4] ; 2) corticosteroid infiltrations improves the symptoms in the majority of patients, but numerous cases of tendon rupture have been reported [5][6][7]; 3) shock waves, recently becomed popular to treat soft tissue disorders, have given ambiguous results in the latest published evidences mainly due to different protocols applied [8,9]. ...
Article
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Background: The advancement of physiopathological knowledge of tendon structures has shown that, in conditions of overload, there is the onset of both degenerative phenomena, such as the production of metalloproteases, apoptosis of tendon cells and neoangiogenesis, and regenerative and protective phenomena, such as the production of IGF-1 and nitric oxide. Tendinopathy results from the imbalance between these two groups of factors, leading to degeneration, weakening, and fissuring of the tendons, with the presence of local pain. The aim of the study was to evaluate the efficacy and tolerability of cetylated fatty acids (CFA) patch formulation in the control of acute localized shoulder pain and recovery of function in patients with tendinopathies. Methods: A prospective, single-center, no-profit observational study conducted in accordance with Good Clinical Practice. Thirty patients with recent onset shoulder pain symptoms (1-3 months) related to bursitis and tenosynovitis, with a diagnosis of shoulder tendon pathology confirmed by ultrasound examination, was evaluated for shoulder pain and function using the Constant Murley Score. Patients used 1 patch containing CFA for 8 h per day for 10 days. At 10 (V1) and 35 (V2) days after the first visit (V0), the Constant Score, treatment compliance and product tolerability were evaluated. Results: Thirty patients completed the treatment. At V0 the mean Constant Score (CS) was 32.37 ± 11.86, during V1 the mean CS was 50.68 ± 14.30, and at V3 the mean CS was 51.07 ± 15.29. The CS increased significantly between V0 and V1 (p < 0.0001) but did not vary significantly between V1 and V2 (p = 1). The tolerability of the product was excellent. Conclusions: Application of the CFA-based patch for 10 consecutive days in patients with shoulder tendinopathies was effective in reducing local pain and resulted in a good recovery of function. The results achieved at day 10 were maintained for 25 days, until the follow-up visit at day 35. CFA-based patch, thanks to their efficacy and tolerability, seems to be a promising solution to improve pain and functionality in subject with shoulder tendinopathy. Trial registration: The study was approved by the Ethics Committee of Azienda USL Toscana Nord Ovest (protocol code 2018RIAB105) and conducted in accordance with Good Clinical Practice and the ethical principles outlined in the Declaration of Helsinki.
... Although the etiology is imperfectly understood, the path physiology is one of the degeneration and necrosis at the pathological site [1]. There are several treatment modalities currently used in clinical practice, including physical therapy, non-steroidal anti-inflammatories, and injections of corticosteroid and platelet-rich plasma (PRP) [2][3][4]. However, no universally accepted treatment is known to be completely safe and effective with a high degree of predictability. ...
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Background: Tendinopathy is a common clinical pathology, with mixed treatment results, especially when chronic. In this study, we examine the effects of an ultrasonic debridement modality in a rabbit tendinopathy model. We asked four questions: 1) Was it possible to create and visualize with ultrasound a tendinopathy lesion in a rabbit Achilles tendon? 2) Was it possible to guide a 19-gauge ultrasonic probe into the tendinopathy lesion? 3) Following ultrasonic treatment, was tendinopathy debris histologically present? and 4) Was the collagen profile qualitatively and quantitatively normalized following treatment? Methods: Skeletally mature female New Zealand white rabbits (n = 12) were injected with, ultrasonography localization, 0.150 ml of collagenase into the Achilles tendon. The collagenase-induced Achilles tendinopathy (3 weeks) was treated with percutaneous ultrasonic debridement. The tendons were harvested, at 3 weeks after treatment, and were subjected to histological assessment (modified Movin score) and biochemical analysis (collagen isoform content). Results: Histopathological examination revealed that all tendons injected with collagenase showed areas of hypercellularity and focal areas of tendon disorganization and degeneration. The treated tendons had lower (improved) histopathological scores than injured tendons (P < 0.001). Western blot analysis showed that ultrasonic therapy restored, within statistical limits, collagen type I, III, and X expressions in a treated tendon, to qualitative and semi-quantitative levels of a normal tendon. Conclusions: We were successfully able to create a collagenase-injected tendinopathy lesion in a rabbit Achilles tendon and visualize the lesion with an ultrasound probe. A 19-gauge ultrasonic probe was inserted into the tendinopathic lesion under direct ultrasound guidance, and minimal tendinopathic debris remained after treatment. The treated tendon demonstrated a normalized qualitative and semi-quantitative collagen profile and improved histological appearance in the short term. This technique demonstrates scientific merit with respect to the minimally invasive treatment of tendinopathy and warrants further studies. Clinical relevance: Recalcitrant tendinopathy has evaded consistent non-operative treatment since the tendinopathic debris remains in situ, to some extent, with non-operative approaches. This percutaneous emulsification/evacuation approach, under direct ultrasound visualization, has the potential to cure recalcitrant tendinopathies without open surgery, which would benefit the patient and result in significant healthcare cost reductions.
... Os anti-inflamatórios orais têm benefício apenas quando considerados no curto prazo e podem afetar o processo de regeneração do tendão a longo prazo. 27 O tratamento da tendinopatia rotuliana com maior nível de evidência é o exercício terapêutico, em particular o exercício excêntrico, isométrico e de contrações isotónicas em velocidade de execução baixa, mais conhecido por heavy slow resistance training (HSRT), o qual envolve elementos concêntricos e excêntricos. A fisioterapia tem um papel essencial, devendo o programa ser estruturado em fases e a progressão adaptada à fase da lesão e às necessidades do atleta. ...
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... Finding something to accelerate tissue healing is important, not only for athletes but also for general people who suffer from tendinopathy, osteoarthritis, acute muscle injuries, etc. Despite the limited scientific evidence, musculoskeletal practitioners began using PRP for the management of cartilage problems as early as 2003 [4,5]. ...
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... The efficacy of both of these anti-inflammatory modalities continues to be debated [59]. Although shown to produce shortterm pain relief, they have also been shown to cause tissue damage [60], increase risk of tendon rupture [61], and negatively impact long-term tendon healing [59]. While some HCPs expressed an awareness of these deleterious effects [46,51], subjectively identified determinants, such as adequate engagement with rehabilitation, or a previous positive outcome with a CSI, appeared to strongly inform decision-making, at times superseding evidence-based recommendations [46]. ...
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Chapter
Tendon and ligament tissues have limited healing capacity. The incidence of injuries and unsatisfactory functional outcomes of repair have been a major driving force in the search for alternative therapeutic approaches envisioning regeneration. Promotion of the healing and regeneration processes is the main scientific rationale for the use of orthobiologic therapies. At present, the traditional outcomes of injury management are suboptimal, especially in the case of tendons, and may benefit from biological augmentation or intervention during the tendon healing process. A better understanding of the complex cellular environments during healing could promote the development of new successful therapies. The present optimization strategies are at an early stage of development, and great importance has been given to identifying key molecular and cellular processes involved in the progression of tendinopathy. Tissue engineering approaches are considered options, though none can yet be considered conclusive in their reproduction of a safe and successful long-term solution for full microarchitecture and biomechanical tissue recovery. In vitro differentiation techniques are not yet fully validated.
Article
The term tendinopathy indicates a wide spectrum of conditions characterized by alterations in tendon tissue homeostatic response and damage to the extracellular matrix. The current pharmacological approach involves the use of nonsteroidal anti-inflammatory drugs and corticosteroids often with unsatisfactory results, making essential the identification of new treatments. In this study, the pro-regenerative and protective effects of an aqueous fibroin solution (0.5–500 μg/mL) against glucose oxidase (GOx)-induced damage in rat tenocytes were investigated. Then, fibroin anti-hyperalgesic and protective actions were evaluated in two models of tendinopathy induced in rats by collagenase or carrageenan injection, respectively. In vitro, 5–10 μg/mL fibroin per se increased cell viability and reverted the morphological alterations caused by GOx (0.1 U/mL). Fibroin 10 μg/mL evoked proliferative signaling upregulating the expression of decorin, scleraxin, tenomodulin (p < 0.001), FGF-2, and tenascin-C (p < 0.01) genes. Fibroin enhanced the basal FGF-2 and MMP-9 protein concentrations and prevented their GOx-mediated decrease. Furthermore, fibroin positively modulated the production of collagen type I. In vivo, the peri-tendinous injection of fibroin (5 mg) reduced the development of spontaneous pain and hypersensitivity (p < 0.01) induced by the intra-tendinous injection of collagenase; the efficacy was comparable to that of triamcinolone. The pain-relieving action of fibroin (peri-tendinous) was confirmed in the model of tendinopathy induced by carrageenan (intra-tendinous) where this fibrous protein was also able to improve tendon matrix organization, normalizing the orientation of collagen fibers. In conclusion, the use of fibroin in tendinopathies is suggested taking advantage of its excellent mechanical properties, pain-relieving effects, and ability to promote tissue regeneration processes.
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Oynanmaya başladığı ilk günden bugüne, büyük değişim ve gelişim gösteren kadın futbolu, istatistiklere göre Avrupa’nın 1 numaralı kadın takım sporu konumundadır. Kadın futbolunun lokomotif organizasyonlarının başında, 2001 yılından bu yana üst düzey kulüpler arasında düzenlenmekte olan “UEFA Kadınlar Şampiyonlar Ligi” (UWCL) gelmektedir. Bu düzeyde büyük ölçekli turnuvaların, bir sporun gelişimine önemli katkılar sağladığı bilinmektedir. Son yıllarda UEFA’nın reform niteliğinde yaptığı uygulamalarla büyük değişime uğrayan turnuva; futbolculara daha çekici bir ortam, seyircilere daha kaliteli futbol, kulüplere ise daha büyük ekonomik katkılar sunmayı hedeflemektedir. Futbol otoriteleri, UEFA Kadınlar Şampiyonlar Ligi’nin parlayan bir organizasyon olma yolunda ilerlediğini değerlendirmektedirler. Araştırmamızda, kadın futbolunun en önemli organizasyonlarından biri olan UEFA Kadınlar Şampiyonlar Ligi’nde oynanan müsabakalarının istatistiki yönden analiz edilmesi amaçlanmıştır. Çalışma, güncel durumun ortaya konulabilmesi amacıyla 2018-2019, 2019-2020 ve 2020-2021 sezonları ile sınırlandırılmıştır. Verilerin toplanması aşamasında Union of European Football Associations (UEFA) resmi web sitesi kayıtları esas alınmıştır. Araştırmaya konu toplam 325 müsabakaya ilişkin resmi müsabaka raporları incelenmiş ve elde edilen veriler SPSS 25.0 programına aktarılmıştır. Analiz yöntemi olarak tanımlayıcı istatistikler kullanılmıştır. Araştırma bulguları ışığında öne çıkan önemli sonuçlar şöyledir; UEFA Kadınlar Şampiyonlar Ligi’nde ev sahibi takım olma avantajının kazanmaya olan etkisi %7,4’dür. Deplasman takımlarının ev sahibi takımlara oranla daha fazla sarı kart gördüğü, kırmızı kartlarda ise anlamlı bir farklılık bulunmadığı tespit edilmiştir. En sık rastlanılan skorlar, ev sahibi takımların 2-0’lık ve deplasman takımlarının 1-0’lık galibiyetleridir. Oynanan hemen hemen her müsabakada gol atıldığı ve golsüz biten müsabakaların oranının sadece %1,2 olduğu saptanmıştır. Müsabaka başı gol ortalaması 3,94 olarak bulunmuştur. Gollerin önemli bir bölümünün müsabakaların son 15 dakikası ve ikinci yarının sonuna eklenen ilave süre içerisinde atıldığı tespit edilmiştir. Yaklaşık dört müsabakadan birinde takımların beş veya daha farklı galibiyetler elde ettiği izlenmektedir (%22,5). Gol, izleyicileri futbol müsabakalarını seyretmeye yönelten unsurların başında gelmektedir. Ancak, liglerde farklı skorların sıklıkla yaşanması, bu kez müsabakaları sıkıcı bir hale getirebilir ve izleyiciyi seyirden uzaklaştırabilir. Yüksek farklı skorların sayıca fazla oluşunun, UEFA Kadınlar Şampiyonlar Ligi’nde yer alan takımlar arasındaki güç dengesizliğini gösterir nitelikte olduğu söylenilebilir. Son yıllarda önemli kulüplerin kadın futbol takımlarını kurmasının, yakın gelecekte saha içi rekabeti arttıracağı ve güç dengesinin sağlanması yolunda önemli düzeyde katkılar sağlayacağı öngörülmektedir.
Chapter
Pathology of the peroneal tendons is an underdiagnosed cause of lateral ankle pain. Tendinopathy of the peroneal tendons can be acute or chronic. Tendon partial tears can also occur. Physical exam and the use of radiographs, ultrasound, and magnetic resonance imaging (MRI) verify the pathology suspected based on the patient’s history and symptoms. Nonoperative management such as immobilization, bracing, nonsteroidal anti-inflammatory drugs (NSAIDs), lateral heel wedges, and physical therapy is traditionally attempted first for the management of tendinopathy. For patients who fail nonoperative management, there are several surgical options available including tendon debridement, tenosynovectomy, tendon tubularization, tendon grafting, or tenodesis. Depending on the pathology type, associated conditions including peroneal tendon subluxation, os perineum syndrome, cavovarus deformity, and lateral ankle instability should be addressed at the time of surgical management. Routine arthroscopic evaluation of the ankle is also recommended at the time of surgery to address any significant intraarticular pathology. With appropriate management, patients with pathology of the peroneal tendons have good outcomes.
Article
Tendon disorders are a major problem for participants in competitive and recreational sports. To try to determine whether the histopathology underlying these conditions explains why they often prove recalcitrant to treatment, we reviewed studies of the histopathology of sports-related, symptomatic Achilles, patellar, extensor carpi radialis brevis and rotator cuff tendons. The literature indicates that healthy tendons appear glistening white to the naked eye and microscopy reveals a hierarchical arrangement of tightly packed, parallel bundles of collagen fibres that have a characteristic reflectivity under polarised light. Stainable ground substance (extracellular matrix) is absent and vasculature is inconspicuous. Tenocytes are generally inconspicuous and fibroblasts and myofibroblasts absent. In stark contrast, symptomatic tendons in athletes appear grey and amorphous to the naked eye and microscopy reveals discontinuous and disorganised collagen fibres that lack reflectivity under polarised light. This is associated with an increase in the amount of mucoid ground substance,which is confirmedwithAlcian blue stain. At sites of maximal mucoid change, tenocytes, when present, are plump and chondroid in appearance (exaggerated fibrocartilaginous metaplasia). These changes are accompanied by the increasingly conspicuous presence of cells within the tendon tissue, most of which have a fibroblastic or myofibroblastic appearance (smooth muscle actin is demonstrated using an avidin biotin technique). Maximal cellular proliferation is accompanied by prominent capillary proliferation and a tendency for discontinuity of collagen fibres in this area.Often, there is an abrupt discontinuity of both vascular and myofibroblastic proliferation immediately adjacent to the area of greatest abnormality. The most significant feature is the absence of inflammatory cells. These observations confirmthat the histopathological findings in athletes with overuse tendinopathies are consistent with those in tendinosis — a degenerative condition of unknown aetiology. This may have implications for the prognosis and timing of a return to sport after experiencing tendon symptoms. As the common overuse tendon conditions are rarely, if ever, caused by ‘tendinitis’, we suggest the term ‘tendinopathy’ be used to describe the common overuse tendon conditions.We conclude that effective treatment of athletes with tendinopathiesmust target the most common underlying histopathology, tendinosis, a noninflammatory condition.
Article
Mechanical and chemical properties were studied in established and in newly formed collagenous tissues of rats after 10 days' treatment with various doses of acetylsalicylic acid, phenylbutazone and indomethacin. Breaking strength of femur bone, tensile strength of femoral epiphyseal cartilage, tensile strength of skin, tensile strength of tail tendons and tensile strength of granulomas induced by implantation of glass rods were measured. Soluble fractions of collagen, insoluble and total collagen were estimated. Glycosaminoglycan fractions were determined by papain digestion, cetylpyridinium chloride precipitation and column chromatography. High doses of each of the antirheumatic drugs induced an increase of strength in all collagenous tissues. However, the degree of the increase and the sensitivity to low doses varied greatly between the different organs. Tail tendons showed an increase of tensile strength with low doses and gave steep dose response curves for each drug. Tensile strength of skin also paralleled dose response curves. Tensile strength of femoral epiphyseal cartilage showed a considerable dose-dependent increase with acetylsalicylic acid but not with indomethacin and phenylbutazone. In glass rod granuloma high doses resulted in a rise of tensile strength. Breaking strength of bones was only slightly changed even by high doses. In each tissue the increase of strength was associated with an increase of insoluble and total collagen whereas the soluble fractions remained almost unchanged. No significant changes of glycosaminoglycan fractions have been found. The results were compared with the effects of corticosteroids and D-penicillamine observed in earlier studies.
Article
70 consecutive adult, nonrheumatic patients with a painful achilles tendinopathy were randomized to treatment with either a nonsteroid antiinflammatory drug (piroxicam) or placebo. Both groups received adjunct treatment with a period of rest combined with stretching and strengthening exercises. 52/70 cases were engaged in various sports, notably running. All subjects were evaluated on days 3, 7, 14, and 28 with respect to pain, tenderness, swelling, ankle joint movement and muscle strength. Results were judged from residual symptoms and an overall assessment of the efficacy. No differences were seen between the groups at any time during the study. The overall result was identical with a rate of success slightly better than 50 percent which corresponds to the placebo response reported in other studies.
Article
This article provides a background for the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in sports medicine, including the nature of the drugs, the settings and rationale for their use, and concerns about their general safety. The criteria for the ideal study to examine the efficacy and safety of NSAIDs after acute injury is then enumerated, including a review of how many of the published studies have met each of the major criteria. Selected studies are described to demonstrate those that have or have not provided the basis for a rational decision on the use of NSAIDs in sports medicine and in the treatment of tendinitis. Finally, this article draws conclusions based on these published studies.
Article
The healing response after tendon injury is defined by cell matrix adaptive capability. There are distinct macrotraumatic and microtraumatic injury patterns and a spectrum of pathologic responses from inflammation to tissue degeneration, as characterized by the tendinosis phenomenon. Epigenetic and genetic factors govern recovery from tendon injury. The potential for future modulation of injury repair by protein mediators or growth factors appears promising.
Article
A double-blind study was carried out in 120 patients who had received soft tissue injuries within the preceding 48 hours to compare the effectiveness of naproxen gel (10%) with placebo gel (base alone). The injuries were predominantly synovitis and tendinitis. Standard clinical evaluations of the patients' condition were made by physicians and patients on entry and after 3 and 7 days of treatment. Both treatments resulted in a significant improvement in symptoms, but naproxen gel was significantly superior to placebo gel (p less than 0.05). The response produced by naproxen was more rapid; all symptoms were significantly improved by Day 3 (p less than 0.05). The greater efficacy of naproxen was reflected in a lower usage of active drug compared with placebo which was consistent throughout the study. While the physicians' global assessments of the two gels did not differ significantly, the patients showed a preference in favour of naproxen (p less than 0.05) Naproxen gel was well tolerated; only 1 adverse event of itching occurred. It is suggested that naproxen gel offers an effective and convenient alternative to systemic non-steroidal anti-inflammatory drugs for patients where side-effects are to be avoided or when oral administration is undesirable.
Article
Because infiltration of mononuclear cells and fibroblast proliferation are associated in chronic inflammatory lesions, we tested the hypothesis that leukotrienes (LT), a product of activated mononuclear cells, may modulate fibroblast growth. Proliferation of cultured human skin fibroblasts was estimated by [3H]thymidine incorporation and cell count at increasing concentrations (0.1 nM to 0.1 microM) of LTC4 or LTD4. LTC4 and LTD4 stimulated cell growth in a dose-dependent manner only in the presence of 50 microM indomethacin. Under similar conditions, LTE4 but not LTB4 (0.1 microM) was active. Both asynchronous, growing cells and synchronous, quiescent cells were sensitive to LT when prostaglandin (PG) synthesis was suppressed by indomethacin. Other blockers of cyclooxygenase such as ibuprofen and aspirin exhibited identical permissive activity, and the effect of indomethacin was totally abolished by addition of PGE2. LTC4 modified neither [3H]arachidonic acid release from prelabeled fibroblasts nor PGE2 production by fibroblasts. These results demonstrate that the sulfidopeptide LT stimulate fibroblast proliferation only when the endogenous synthesis of PG is blocked, but they do not enhance the synthesis of PG in their target cells showing no evidence for a negative feed-back loop. Nevertheless, it seems likely that the initiation and development of the fibrotic process in the different tissues depends in part on the local balance between PG and LT productions.
Article
Strong statements regarding the efficacy of anti-inflammatory medication are based primarily on experience with rheumatic disease. Such experience, over 32 years, involving more than 400,000 injections in more than 12,000 patients, has led Hollander and associates to conclude that "no other form of treatment for arthritis has given such consistent local symptomatic relief in so many for so long with so few harmful effects." Such endorsement has not been clearly transferrable to sports medicine experience. Anti-inflammatory medications can unquestionably affect excessive inflammation. Whether this tissue effect is significant with regard to enhancing sports performance has been difficult to prove. To quote Oriole baseball pitcher Jim Palmer, "cortisone is a miracle drug ... for a week!" Perhaps this is because in rheumatologic disease, inflammation is the problem, whereas in sports injury, performance recovery depends on restoration of both the injured tissue and its kinetic environment. The tendency to place an inflammatory label (i.e., "itis") on sports-induced pain has promoted the value of anti-inflammatory treatment while risking a de-emphasis of the role of physical rehabilitation and even well-timed surgical repair. If pain and signs of inflammation are persistent, repeated efforts to turn off the body's alarm is not a substitute for finding the cause of the fire. Indeed, to remove the "fire alarm" of pain from the onset of an injury can clearly place the athlete in great jeopardy with respect to tissue overload and failure. Perhaps the greatest criticism that can be raised regarding anti-inflammatory treatment as a sole solution in sports injury is that it tends, in its worst application, to be too passive and dependent a modality and does not challenge the athlete's sense of responsibility to properly train, condition, and develop correct technique. Thus, anti-inflammatory therapy may succeed only if the patient has been instilled with the proper expectations and responsibilities. Increasing knowledge of the pathobiology of sports injury and the various treatments required for complete recovery has led the experienced clinician to rely far less upon anti-inflammatory medication as a long-term solution. Nevertheless, until more biologically selective drugs become available, the judicious application of anti-inflammatory therapy remains a useful, albeit adjunctive therapy for sports injury. The successful clinical rationale is best arrived at not by random selection but by cautious individualized prescription.