Syfte - Syftet med denna systematiska litteraturstudie var att sammanställa forskning som utvärderar effekten av excentrisk träning samt jämföra excentrisk träning med alternativ behandling på smärta och funktion vid kronisk patellar tendinopati. Frågeställningar 1. Vilken evidens finns idag för att excentrisk träning minskar smärta och förbättrar funktion hos personer med patellar tendinopati? 2. Vilken evidens finns idag för att excentrisk träning är mer effektiv gällande smärta och funktion jämfört med andra behandlingsstrategier hos personer med patellar tendinopati? Metod Sökning av litteratur gjordes i PubMed, Web of Science, Cinahl och AMED. 12 artiklar valdes ut för granskning enligt PEDro scale. Poängbedömningen omsattes till SBUs mall för bevisvärde för evidensgrad och sammanställdes i tabellform med rubrikerna syfte, urval, metod, statistik, resultat, slutsats och primära utfallsvariabler. Resultat Resultatet av denna litteraturstudie visar en indikation på att excentrisk träning minskar smärta och ökar funktion hos personer med patellar tendinopati. Jämfört med annan behandling är excentrisk träning lika effektivt som kirurgi, Heavy Slow Resistance och mer effektiv än kortisoninjektion vid långtidsuppföljning. En artikel hade högt bevisvärde och elva medelhögt. Slutsats Nuvarande forskning ger en indikation på att excentrisk träning ger en minskning av smärtan och ökad funktion hos personer med patellar tendinopati, dock kan man om möjligheten finns använda sig av andra behandlingsmetoder som visat sig ge samma effekt. För att säkerställa effekten gentemot andra behandlingsmetoder behövs fler studier med hög kvalité som jämför samma metoder. I dagsläget är det för få studier som faktiskt jämför samma saker vilket gör det svårare att med säkerhet säga att excentrisk träning är bättre än annan behandling. / Aim - The purpose of this systematic review was to compile research evaluating the effect of eccentric training and compared with alternative therapy, on pain and function in patients with chronic patellar tendinopathy. Method - Search of the literature was done in PubMed, Web of Science, Cinahl and AMED. 12 articles were selected for review using the PEDro scale. Points assessment were traded with SBU template probative value of evidence level and summarized in tabular form. Results - The results of this study showed that eccentric training reduces pain and increases function of patients with patellar tendinopathy. Compared to other treatments eccentric training is as effective as surgery, Heavy Slow Resistance and more effective than cortisone injection at long term follow-up. Also more effective than friction and ultrasound. One article had high quality and the rest medium quality. Conclusions -Current research provides an indication that eccentric exercise results in a decrease in pain and improved function in patients with patellar tendinopathy, however, the use of other therapies has proven to give the same effect and can be used if there is a possibility to. To ensure efficacy against other treatments more studies with high quality comparing the same methods are needed. In the current situation there are too few studies that actually compare the same things which make it difficult to say with certainty that eccentric training is better than any other treatment.

BACKGROUND: Osteoarthritis is a leading cause of disability in people of 65 and older. Researches have shown several possible factors leading to knee osteoarthritis development. Patellofemoral joint maltracking has been thought to be associated with or caused edema in the knee; which is thought to be the early signs of osteoarthritis. Hoffa's fat pad is an intra-articular component of knee located under the kneecap. It has also been suggested as one marker for osteoarthritis, when MRI shows a presence of edema in it. Recently, edema in the superolateral region of Hoffa's fat pad has been hypothesized as a distinct signal than the edema on other regions. There is an interest in finding the relation of this superolateral edema with other factors of osteoarthritis development. OBJECTIVE: This thesis research project is aimed to assess the relation of kneecap-thighbone (patellofemoral) joint alignment, femoral trochlea morphology, and patellar height to edema in the superolateral region of Hoffa’s fat pad especially in the population with average age above 65 years old. The hypothesis is that the flatter trochlear morphology and abnormal patella alignment will have higher risk of superolateral edema. METHODS: This is a cross-sectional study using a subset data from Multicenter Osteoarthritis (MOST) study, specifically at 60-month visit. This study measured the patellofemoral measurements (sulcus angle, lateral and medial trochlear inclination angle, trochlear angle, Insall-Salvati ratio, patellar tilt angle, and bisect offset) as the predictor variables, and semiquantitative scoring of MRI edema in superolateral Hoffa’s fat pad as the outcome variable. Logistic regression analyses were performed to find the strongly associated patellofemoral measurements to superolateral Hoffa’s fat pad edema. RESULTS: From the logistic regression analysis, trochlear angle, Insall-Salvati ratio, and bisect offset were highly associated with the superolateral edema. A further analysis, by categorizing the measurements to quartiles, was found that only the highest quartiles of both bisect offset and trochlear angle are associated with superolateral Hoffa’s fat pad edema when compared to the reference quartile. All quartiles of Insall-Salvati ratio are strongly associated with superolateral edema when compared to the reference quartile. CONCLUSION: Current study presents that people above 65 years old with high trochlear angle, extreme lateral patellar translation or bisect offset, and high patella riding have high risk of having superolateral Hoffa’s fat pad edema.

Thesis (MScPhysio)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: This review aims to present the available evidence for the effect of McConnell taping on knee biomechanics in individuals with Anterior Knee Pain (AKP). Pubmed, Medline, Cinahl, Sportdiscus, Pedro and Science Direct electronic databases were searched from inception until September 2014. Experimental research into knee biomechanical or EMG outcomes of McConnell taping compared to no tape or placebo tape were included. Two reviewers completed the searches, selected the full text articles and assessed the risk of bias of eligible studies. Authors were contacted for missing data. Eight heterogeneous studies with a total sample of 220 were included in this review. All of the studies had a moderate to low risk of bias and compared taping to no tape and/ or placebo tape. Pooling of data was possible for three outcomes; average knee extensor moment, average VMO/VL ratio and average VMO-VL onset timing. None of these outcomes revealed significant differences. The evidence is currently insufficient to justify the routine use of the McConnell Taping technique in the treatment of Anterior Knee Pain. There is a need for more evidence on the aetiological pathways of Anterior knee Pain; level one evidence and studies investigating other potential mechanisms of McConnell taping. / AFRIKAANSE OPSOMMING: Die objektief van hierdie resensie was om te bepaal wat die effekte van McConnell Patellar Vasbinding is op knie kinematika, kinetiek en spier aktivering in diegene met Voorafgaande Knie Pyn (VKP). Die navorsers het elektroniese databases soos Pubmed, Medline, Cinahl, Sportdiscus, Pedro en Science Direct, van aanvang tot September 2014, ondersoek. Eksperimenteel studie ontwerpe wat biomeganiese of EMG gevolge van McConnell Vasbinding vergelyk met geen vasbinding of placebo vasbinding, is ingesluit. Twee resente het die ondersoek voltooi, die volle tekse artikels gekies en die partydigheid risiko van die ingeslote studies, geskat. Skrywers is gekontak vir enige verlore data. Agt heterogeen studies uit ‘n totalle monster van 220 is in hierdie resensie ingesluit. Al die studies het ‘n gematigde tot laag risiko vir eensydigheid en vergelyk vasbinding met geen of placebo vasbinding. Data saamvoeging was moontlik vir drie uitslae, naamlik: gemiddelde knie ekstensor moment; gemiddelde VMO/VL ratio en gemiddelde aanval tydmeting. Geen gevolge het veelseggende verskille of afwykings vertoon. Tans is die bewys nie genoegsaam om die routiene gebruik van McConnell Vasbinding tegniek te regverdig nie in die behandeling van VKP. Meer bewyslewering op die etiologiese paaie van VKP; Graad een bewys en studies wat ander moontlike meganisme van Mc Connell Vasbinding ondersoek, is noodsaaklik.

Articular cartilage damage and degeneration is a siginficant clinical problem which no technique has been able to adequately and reliably repair or regenerate. Recent research has investigated the use of cell-based therapies to treat focal cartilage lesions. In clinical practice proliferated autologous chondrocytes are used and clinical trials are investigating the use of mesenchymal stem cells. The aim of this thesis was to assess aspects of current cell-based therapy and to investigate the potential of perivascular stem cells for articular cartilage repair. The phenotype of expanded matrix-applied autologous chondrocytes utilised in current cell therapies was confirmed using immunocytochemistry and polymerase chain reaction (PCR) expression of hyaluronan and proteoglycan link protein 1 (HAPLN1), transcription factor sox-9 (SOX9) and aggrecan (ACAN). Quantitative real-time PCR demonstrated that they were down-regulated for expression of COL2A1, SOX9 and ACAN but up-regulated for COL1A1 compared to unproliferated chondrocytes. Confocal laser-scanning microscopy (CLSM) demonstrated a significant decrease in cell viability and density when the membranes were subjected to levels of trauma similar to those that could be experienced during surgery. Hyperosmolar solutions did not confer a chondroprotective effect. Pericytes and adventitial cells, collectively termed perivascular stem cells (PSCs), from the infra-patellar fat pad were identified using immunohistochemistry and isolated using enzymatic digestion and fluorescence-activated cell sorting (FACS). Cell identity was ascertained using PCR, FACS and mesenchymal differentiation (osteogenesis, adipogenesis and chondrogenesis). Quantitative real-time PCR analysis of micromass cultures indicated that PSCs displayed increased chondrogenic potential compared to mesenchymal stem cells. An ovine model of perivascular stem cells was developed and a pilot study using three sheep was undertaken to confirm the viability of the model. Autologous ovine PSCs were isolated and re-implanted into articular cartilage defects. Green fluorescent protein transfected cells were identified in the cartilage defect four weeks following re-implantation using CLSM. This thesis has examined aspects of matrix-applied autologous chondrocyte implantation for cell based cartilage repair and has identified a new source of prospectively identified and purified stem cells that have demonstrated increased chondrogenic potential compared to mesenchymal stem cells, which are commonly used in clinical research. The methods to identify and purify ovine perivascular stem cells were developed to investigate the use of autologous PSCs and to track the cells following implantation.

INTRODUÇÃO: A ultrassonografia (US) e a ressonância magnética (RM) representam os principais métodos de diagnósticos por imagem na avaliação do mecanismo extensor do joelho. Há carência de trabalhos que avaliem por US e RM a presença de alterações no mecanismo extensor de jogadores de futebol assintomáticos. OBJETIVO: Avaliar, por meio de RM e US, o tendão quadríceps e o ligamento patelar de jogadores de futebol assintomáticos e dos participantes do grupo-controle. Identificar se há alterações de imagens ou lesões. Determinar se essas sofrem influências pelos seguintes critérios: canhoto ou destro, quanto à dominância ao chute, posição em campo, idade do atleta e tempo de prática esportiva. MÉTODO: Foram avaliados um total de 248 joelhos: 112 eram de 56 de jogadores de futebol assintomáticos e 136 eram do grupo-controle. O grupo composto por jogadores de futebol apresentava idades entre 14 e 34 anos. Já o grupo-controle era composto por indivíduos com idade também entre 14 e 34 anos, principalmente, universitários e funcionários do hospital, com gênero igual aos dos jogadores selecionados, mas sem atividades físicas de impacto, como vôlei, futebol e salto, por exemplo. RESULTADO: Constatou-se a presença de alterações de imagens ou de lesões em nove ligamentos patelares e apenas duas nos tendões quadríceps de jogadores de futebol assintomáticos, tanto pela US quanto pela RM, e nenhum caso alterado no grupo-controle. Houve concordância significativa entre RM e US quanto aos resultados obtidos. Além disso, os jogadores de futebol apresentaram anormalidades (alterações de imagens ou lesões) no tendão quadríceps ou no ligamento patelar significativamente (p<0,05) maior do que no grupo-controle; a idade média dos jogadores com alguma anormalidade é significativamente menor do que a dos jogadores sem lesão (p<0,003); o tempo médio de prática desportiva dos jogadores que apresentam anormalidade é menor do que o tempo médio dos jogadores que não têm anormalidade (p<0,001); os jogadores destros apresentaram anormalidades, enquanto que os jogadores canhotos não (p<0,05). Dentre os jogadores, há correlação entre mais alterações de imagem ou lesão de joelho e menor tempo como jogador e menor idade (R² de Nagelkerke = 0,700). Destros têm risco aumentado de ter anormalidade nas referidas estruturas (Razão de Chances = 15,204) quanto menor for o tempo como jogador de futebol. Os jogadores da defesa têm 4,76 vezes mais chance de desenvolver anormalidade do que atacantes e goleiros (p<0,04). CONCLUSÃO: Os jogadores de futebol assintomáticos apresentam anormalidades no tendão do quadríceps e ligamento patelar detectadas pela RM e US. As alterações estão relacionadas a menor idade, menor tempo de prática desportiva, ser destro e ser jogador de defesa / INTRODUCTION: Ultrasonography (US) and magnetic resonance imaging (MRI) are the main diagnostic imaging methods used in evaluation of the extensor mechanism of the knee. Theres a scarcity of works assessing alterations on the extensor mechanism of the knee of asymptomatic soccer players using US and MRI. OBJECTIVE: To assess, by means of MRI and US imaging, the quadriceps tendon and patellar ligament of asymptomatic soccer players and healthy control group; identify abnormal imaging findings or injuries; ascertain whether these are affected by leg dominance (left or right), field position, age, and time spent practicing the sport. METHOD: A total of 248 knees were evaluated: 112 of 56 asymptomatic soccer players and 136 of healthy controls. The players ages ranged from 14 to 34 years. The control group was composed mostly of college students and hospital staff members, also with ages between 14 and 34, matched for gender to the selected soccer players, and who did not engage in high-impact activities such as volleyball, soccer, or jumping. RESULTS: Abnormal imaging findings or injuries were detected, by US and MRI alike, in nine patellar ligaments and two quadriceps tendons of asymptomatic soccer players. No abnormal findings were detected in the control group. CONCLUSION: There was significant consistency between MRI and US findings. Soccer players were much more likely (p<0.05) to have abnormal imaging findings or injuries of the quadriceps tendon and patellar ligament as compared with the control group; the average age of players presenting some abnormality is significantly lower than of those without injuries (p<0.003); the average time spent practicing the sport for players presenting abnormalities is lower than those who dont present injuries (p<0.001); a correlation between the dominant leg and the affected knee was observed, with the players with a dominant right leg presenting injuries while the ones with a dominant left leg not showing abnormalities (p<0.05). Amongst the players there is a correlation between more abnormal imaging findings or injuries on the knee and less professional practicing time and age (Nagelkerke R² = 0.700).Players with a dominant right leg have an increased chance of presenting abnormalities on the quadriceps tendon and patellar ligament (Odds Ratio = 15.204) with a lower average time spent practicing the sport. Defense players have 4.76 times more chance to develop abnormalities than forward players and goalkeepers (p<0.04). CONCLUSION: The asymptomatic soccer players present abnormalities on the quadriceps tendon and patellar ligament identified using ultrasonography (US) and magnetic resonance imaging (MRI). The alterations are related with less age, less time of professional practice, right leg dominance and defense field position

Li Chi Kei. / Thesis (M.Phil.)--Chinese University of Hong Kong,1995. / Includes bibliogrpahical references (leaves 54-68). / Abstract --- p.1 / Acknowledgments --- p.4 / Lists of Figures --- p.5 / List of Tables --- p.8 / Chapter Chapter 1 --- Introduction --- p.9 / Chapter 1.1 --- Ligamental Injury --- p.9 / Chapter 1.2 --- ACL Injury --- p.10 / Chapter 1.3 --- Patellar Tendon and Anterior Cruciate Ligament --- p.11 / Chapter 1.4 --- Patellar Tendon Bone Graft --- p.13 / Chapter 1.41 --- Strength of the Patellar Tendon Bone Graft --- p.13 / Chapter 1.42 --- Use of the Patellar Tendon Bone Graft --- p.14 / Chapter 1.5 --- Patellar Tendon Bone Graft in Anterior Cruciate Ligament Reconstruction --- p.14 / Chapter 1.6 --- Complications of Anterior Cruciate Ligament Reconstruction after the Use of Patellar Tendon Bone Graft --- p.16 / Chapter 1.7 --- Healing of the Patellar Tendon Donor Site --- p.17 / Chapter 1.8 --- Objective of the Study --- p.22 / Chapter 1.9 --- Significance of the Study --- p.22 / Chapter Chapter 2 --- Material & Method --- p.24 / Chapter 2.1 --- Animal Model --- p.24 / Chapter 2.2 --- Grouping --- p.24 / Chapter 2.3 --- Operative Procedure --- p.24 / Chapter 2.4 --- Method of Assessment --- p.26 / Chapter 2.41 --- Gross Morphology --- p.26 / Chapter 2.42 --- Biomechanical Testing --- p.27 / Chapter 2.43 --- Biochemical Assay --- p.28 / Chapter 2.43.1 --- Water Content --- p.29 / Chapter 2.43.2 --- Collagen Content --- p.29 / Chapter 2.44 --- Histology --- p.30 / Chapter 2.45 --- Immunohistochemistry --- p.31 / Chapter 2.5 --- Statistics --- p.32 / Chapter Chapter 3 --- Results --- p.33 / Chapter 3.1 --- Operation Complications --- p.33 / Chapter 3.2 --- Gross Morphology --- p.33 / Chapter 3.21 --- Dimension of the Patellar Tendon --- p.33 / Chapter 3.22 --- Dimension of the Patellar Tendon Bone Graft --- p.33 / Chapter 3.23 --- Dimension of the Remain Patellar Tendon --- p.34 / Chapter 3.24 --- Gross Appearance of the Patellar Tendon Donor Site --- p.35 / Chapter 3.3 --- Biomechanical Testing --- p.36 / Chapter 3.31 --- Failure Load --- p.36 / Chapter 3.32 --- Ultimate Stress --- p.37 / Chapter 3.33 --- Stiffness --- p.37 / Chapter 3.34 --- Energy Absorbed before Failure --- p.38 / Chapter 3.4 --- Biochemical Assay --- p.38 / Chapter 3.41 --- Water Content --- p.38 / Chapter 3.42 --- Collagen Content --- p.39 / Chapter 3 .5 --- Histology & Immunohistochemistry --- p.39 / Chapter 3.51 --- Morphology of Control Tendon --- p.40 / Chapter 3.52 --- Morphology of Experimental Tendon with 'Open' Procedure --- p.40 / Chapter 3.53 --- Morphology of Experimental Tendon with 'Close' Procedure --- p.41 / Chapter 3.54 --- Healing at the Patellar and Tibial Insertion Site --- p.41 / Chapter 3.55 --- Morphology of the Cartilage Surface --- p.42 / Chapter Chapter 4 --- Discussion & Conclusion --- p.43 / Chapter 4.1 --- Gross Morphology --- p.43 / Chapter 4.2 --- Biomechanical Testing --- p.45 / Chapter 4.3 --- Biochemical Assay --- p.47 / Chapter 4.4 --- Histology & Immunohistochemistry --- p.49 / Chapter 4.5 --- Conclusion --- p.51 / References --- p.54 / Figures / Tables / Appendix

In conclusion, the present study firstly addressed the relationship between graft incorporation and peri-graft bone quality and quantity after ACL reconstruction in a rabbit model. The findings suggested that the non-invasive measurement of peri-graft bone would be useful to predict graft incorporation. Peri-graft bone loss was region-specific after surgery, which might be associated with stress shielding in the specific region after tunnel creation. The use of Brushite CPC might be a promising way to augment peri-graft bone and enhance graft incorporation. (Abstract shortened by UMI.) / In the fourth part, brushite CPC was successfully applied to augment the peri-tendon bone volume and connectivity. It was revealed under mechanical testing that the ultimate strength and stiffness of graft fixation in bone tunnel on experimental side was higher than that of the control by 117% and 102% respectively at 6 weeks, postoperatively (p&lt;0.05 for both). The use of brushite CPC caused a paradigm shift in failure mode from intra-tunnel to intra-articular portion at 12 weeks postoperatively (p=0.013). / Keywords. anterior cruciate ligament reconstruction, bone mass, microarchitecture, tendon-to-bone healing, graft incorporation, brushite calcium phosphate cement / The first part of this thesis compared the histological characteristics of T-B healing interface tissue in femoral and tibial tunnels following ACL reconstruction in rabbits. Results revealed that less cartilaginous interface tissue was formed in tibial tunnel than in femoral tunnel. Such cartilaginous tissue was gradually mineralized during reestablishment of a direct T-B integration. T-B healing in tibial tunnel was inferior to that in femoral tunnel. The disparity of T-B healing in various osseous milieus suggested the potential association in between. / The second part of this original work further explored the numeric relationship between the strength of T-B attachment and peri-graft bone mass and connectivity. Results of Micro-computed tomography (micro-CT) showed that peri-graft bone mass and connectivity was significantly lower on tibial side than those on femoral side. It was found under biomechanical evaluation that grafted tendon was prone to be pulled out from tibial tunnel with the bone attachment; the weakest point of the complexes shifted from the healing interface at time zero to peri-graft bone at week 6 after operation. With reverse of peri-graft bone at week 12 postoperatively, the weakest point shifted to intra-osseous tendinous portion. The stiffness of graft fixation correlated with peri-graft BV/TV (r2=0.68, p=0.001) and connectivity (r2=0.47, p=0.013) at week 6 after operation. / The third part addressed the changes of peri-graft bone in spatial and temporal manners using high resoluation multiple-slice peripheral quantitative computed tomography (pQCT) and micro-CT. Under pQCT evaluation, a decrease in BMD was present in specific regions, medial region of femoral tunnel by 26% and posterior and lateral regions of tibial tunnel by 22% and 42%, respectively at week 12 postoperatively than the baseline (p&lt;0.05 for all). It was accompanied by a decrease in trabecular number and increase in trabecular spacing, the shift of plate-like to rod-like trabeculae and loss of anisotropy under micro-CT evaluation. It was echoed by histological findings showing increased osteoclastic activities and poor T-B healing in these specific regions. The postoperative bone loss and associated poor T-B healing was region-specific. / by Wen, Chunyi. / Adviser: Kai-ming Chan. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0217. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 148-168). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

by Wang Wen. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 113-124). / Abstracts in English and Chinese. / ABSTRACT --- p.i / FLOWCHART --- p.vi / ACKNOWLEDGEMENT --- p.x / ABBREVIATIONS --- p.xi / INDEX FOR FIGURES --- p.xii / INDEX FOR TABLES --- p.xv / TABLE OF CONTENTS --- p.xvi / Chapter 1. --- INTRODUCTION --- p.1 / Chapter 1.1 --- PATELLAR TENDINOSIS --- p.1 / Chapter 1.1.1 --- Introduction --- p.1 / Chapter 1.1.2 --- Epidemiology of Patellar Tendinosis --- p.3 / Chapter 1.1.3 --- Etiology of Patellar Tendinosis --- p.3 / Chapter 1.1.4 --- Manifestations of Patellar Tendinosis --- p.4 / Chapter 1.1.5 --- Imaging Examination on Patellar Tendinosis --- p.4 / Chapter 1.1.6 --- Clinical Diagnosis of Patellar Tendinosis --- p.6 / Chapter 1.1.7 --- Management of Patellar Tendinosis … --- p.6 / Chapter 1.2 --- ANATOMY AND HISTOLOGY OF PATELLAR TCNDON --- p.7 / Chapter 1.3 --- STRUCTURE AND METABOLISM OF TENDON --- p.9 / Chapter 1.3.1 --- Tenocytes --- p.9 / Chapter 1.3.2 --- Extra-cellular Matrix --- p.11 / Chapter 1.3.2.1 --- Collagen --- p.11 / Chapter 1.3.2.2 --- Proteoglycans --- p.12 / Chapter 1.4 --- ROLES OF GROWTH FACTORS TENDON HEALING AND REPAIR --- p.14 / Chapter 1.4.1 --- Platelet-Derived Growth Factor --- p.14 / Chapter 1.4.2 --- Transforming Growth Factor-beta --- p.15 / Chapter 1.5 --- HISTOPATHOLOGY OF PATELLAR TENDINOSIS --- p.16 / Chapter 1.6 --- STUDY PLAN --- p.17 / Chapter 1.6.1 --- Characterization on Hypercellularity --- p.18 / Chapter 1.6.2 --- Characterization on Disorganization and Loosening of Collagen --- p.18 / Chapter 1.6.3 --- Characterization on Inflammatory Trace --- p.20 / Chapter 1.6.4 --- Characterization on Growth Factors in Tendinosis --- p.21 / Chapter 1.7 --- OBJECTIVES --- p.22 / Chapter 2. --- MATERIALS AND METHODS --- p.27 / Chapter 2.1 --- HUMAN TISSUES --- p.27 / Chapter 2.1.1 --- Patellar Tendinosis Tissues --- p.27 / Chapter 2.1.1.1 --- Diagnosis of patellar tendinosis --- p.27 / Chapter 2.1.1.2 --- Recruitment of patients --- p.27 / Chapter 2.1.4 --- Healthy Patellar Tendon tissues --- p.28 / Chapter 2.2 --- TISSUES COLLECTION AND PREPARATION --- p.28 / Chapter 2.3 --- HISTOLOGICAL STUDY ON HUMAN SPECIMENS --- p.28 / Chapter 2.3.1 --- Haematoxyline and Eosin Staining --- p.29 / Chapter 2.3.2 --- Safranin O Staining --- p.29 / Chapter 2.3.2.1 --- Reagents preparation --- p.29 / Chapter 2.3.2.2 --- Experimental procedure --- p.30 / Chapter 2.3.5 --- Polarization Microscopy --- p.30 / Chapter 2.4 --- IMMUNOHISTOCHEMICAL STAINING --- p.30 / Chapter 2.4.1 --- Reagents Preparation --- p.31 / Chapter 2.4.2 --- Experimental Procedure --- p.33 / Chapter 2.5 --- IMAGE ANALYSIS --- p.35 / Chapter 2.5.1 --- Equipment --- p.35 / Chapter 2.5.2 --- Procedures --- p.35 / Chapter 2.6 --- IN SITU ZYMOGRAPHY --- p.37 / Chapter 2.6.1 --- Reagents Preparation --- p.37 / Chapter 2.6.2 --- Experimental Procedure --- p.38 / Chapter 2.7 --- STATISTIC ANALYSIS.… --- p.39 / Chapter 3. --- RESULTS --- p.42 / Chapter 3.1 --- HUMAN SAMPLES --- p.42 / Chapter 3.1.1 --- Patellar tendinosis patients --- p.42 / Chapter 3.1.2 --- Healthy control group --- p.43 / Chapter 3.2 --- HISTOLOGICAL STUDY ON HUMAN SPECIMENS --- p.43 / Chapter 3.2.1 --- Gross Morphology --- p.43 / Chapter 3.2.2 --- Haematoxyline and Eosin Staining --- p.44 / Chapter 3.2.3 --- Safranin O Staining --- p.44 / Chapter 3.2.4 --- Polarization Microscopy --- p.44 / Chapter 3.3 --- IMAGE ANALYSIS --- p.45 / Chapter 3.3.1 --- Immunohistochemistry of PCNA --- p.45 / Chapter 3.3.2 --- Immunohistochemistry of hsp47 --- p.46 / Chapter 3.3.3 --- Immunohistochemistry of Procollogen Type I --- p.47 / Chapter 3.3.4 --- Immunohistochemistry of MMP1 --- p.47 / Chapter 3.3.5 --- Immunohistochemistry of TIMP1 --- p.48 / Chapter 3.3.6 --- Immunohistochemistry of COX-2 --- p.49 / Chapter 3.3.7 --- Immunohistochemistry of TGFP --- p.49 / Chapter 3.3.8 --- Immunohistochemistry of PDGFbb --- p.50 / Chapter 3.3.9 --- Immunohistochemistry of PDGFRβ --- p.51 / Chapter 3.3.10 --- Summary of Image Analysis of Immunohistochemical staining --- p.51 / Chapter 3.4 --- IN SITU ZYMOGRAPHY --- p.52 / Chapter 4. --- DISCUSSION --- p.93 / Chapter 4.1 --- DIAGNOSIS OF PATELLAR TENDINOSIS --- p.93 / Chapter 4.2 --- HYPERCELLULARITY IN PATELLAR TENDINOSIS --- p.95 / Chapter 4.3 --- COLLAGEN DISTURBANCE IN PATELLAR --- p.97 / Chapter 4.4 --- INFLAMMATORY RESPONSE IN PATELLAR TENDINOSIS --- p.100 / Chapter 4.5 --- THE EXPRESSION OF GROWTH FACTORS IN PATELLAR TENDINOSIS --- p.102 / Chapter 4.6 --- PROPOSED PATHOGENESIS FOR PATELLAR TENDINOSIS --- p.105 / Chapter 4.7 --- LIMITATION OF THIS STUDY --- p.108 / Chapter 4.8 --- FUTURE STUDY --- p.109 / Chapter 5. --- CONCLUSION --- p.111 / BIBLIOGRAPHY --- p.113

The principal aim of the present thesis was to prospectively follow (clinical status and ultrasound + Doppler findings) the patellar tendons in the young elite volleyball players at the Swedish National Centre for high school volleyball in Falköping. In an Olympic weightlifter with chronic painful jumper´s knee, the effects of treatment with sclerosing injections followed by early instituted very heavy weightlifting training, was also evaluated. First, in a prevalence study, we demonstrated that the clinical diagnosis patellar tendinopathy-jumper’s knee, together with structural tendon changes and vascularisation in the painful area of the tendon, was demonstrated in 12/114 tendons in Swedish junior elite volleyball players, but not in any tendons of individually matched (age, height and weight) not regularly sports active controls. Structural tendon changes alone was demonstrated among the volleyball players but also among the controls. In a 7 months prospective study of a total of 120 tendons, we demonstrated that the clinical diagnosis patellar tendinopathy-jumper’s knee was associated with neovessels/vascularity in the area with structural tendon changes in 17/19 tendons. Seventy tendons that at start were clinically normal, and had normal ultrasound + Doppler findings, remained clinically normal after 7 months with intensive training and playing volleyball. In a 3-year prospective study it was demonstrated that normal clinical tests and normal ultrasound + Doppler findings at school start, indicated a low risk (8%) for these players to sustain patellar tendinopathy-jumper’s knee during the 3 school years with intensive training and playing. In a case study, involving an Olympic elite weightlifter with chronic painful patellar tendinopathy-jumper’s knee, successful treatment with ultrasound and Doppler-guided injection of the sclerosing agent polidocanol, allowed for pain-free very heavy weight training two weeks after treatment. Further heavy weightlifting training on a daily basis, preparing for European Championships, was done without causing tendon rupture and/or pain. Key words: Jumper’s knee, Patellar tendinopathy, Chronic pain, Ultrasonography, Doppler, Neovascularisation, Volleyball, Weightlifting

Tendinosis is a condition of chronic pain that afflicts several human tendons, not least the patellar tendon, in which case it is often clinically referred to as ‘jumper’s knee’. The exact mechanisms behind tendinosis are yet not fully understood. One draw-back in the case of patellar tendinosis has been the lack of knowledge of the innervation patterns of the human patellar tendon. It cannot be excluded that the processes of tendinosis are influenced by nerve mediators, released from nerve endings or from stimulated cells inside the tendon. Thus, the studies of the present thesis aimed to 1) map the general, sensory, cholinergic and sympathetic innervation patterns of the human patellar tendon, in both the tendon tissue proper and the loose paratendinous connective tissue surrounding the tendon, and 2) investigate the possible existence of a production of signal substances, traditionally associated with neurons, in non-neuronal tendon cells, and to see if there are signs of local cholinergic and catecholaminergic signaling pathways. Biopsies of both normal pain-free patellar tendons and patellar tendons from patients with chronic painful tendinosis were collected and investigated. The main method utilized was immunohistochemistry, using antibodies directed against synthesizing enzymes for acetylcholine and catecholamines, against muscarinic and adrenergic receptors, and against markers of general and sensory innervation. In situ hybridization (ISH) to detect mRNA for the cholinergic/catecholaminergic synthesizing enzymes was also used. It was found that the loose paratendinous connective tissue of the patellar tendon was rather richly innervated by nerve structures. These consisted of large nerve fascicles, as well as perivascular innervation in the walls of some of the larger arteries and smaller blood vessels. It was found that part of the nerve structures corresponded to sensory afferents, and that some conformed to cholinergic and, especially, sympathetic nerve fibers. The tendon tissue proper was strikingly less innervated than the paratendinous tissue. The sparse innervation that was found in the tendon tissue proper was seen in narrow zones of loose connective tissue and blood vessels, interspersed between the collagen bundles. The overall impression was that the patterns of distribution of the general, sensory, and autonomic innervations of tendinosis tendon tissue were similar to those of normal tendon tissue proper. The most pioneering findings were the immunohistochemical observations of an expression of enzymes related to production of both acetylcholine and catecholamines within the tendon cells (tenocytes) themselves, as well as of a presence of the receptors for these substances on the same cells; features that were predominantly seen in tendinosis tendons. The observations of the synthesizing enzymes for acetylcholine and catecholamines in tenocytes were confirmed by ISH findings of mRNA for these enzymes in the tenocytes. Immunoreactions for muscarinic and adrenergic receptors were also found in blood vessel walls and in some of the nerve fascicles. In summary, this thesis presents novel information on the innervation patterns of the human patellar tendon, in healthy individuals with pain-free tendons as well as in patients with chronic painful tendinosis. Furthermore, it gives the first evidence of the presence of a local, non-neuronal production in the tendon tissue of signal substances normally seen in neurons, and a basis for these substances to affect the tenocytes as these cells also display muscarinic and adrenergic receptors. Thus, the results indicate an existence of autocrine and/or paracrine cholinergic/catecholaminergic systems in the tendon tissue; systems that seem to be up-regulated in tendinosis. This is of great interest as it is known that stimulation of receptors for both catecholamines and acetylcholine can lead to cell proliferation, interfere with pain sensation, influence collagen production, and take part in vasoregulation, as well as, in the case of adrenergic receptors, promote cell degeneration and apotosis. All these processes represent biological functions/events that are reported to be affected in tendinosis. In conclusion, despite the fact that there is very limited innervation within the patellar tendon tissue proper, it is here shown that effects of signal substances traditionally associated with neurons seem to occur in the tissue, via a local production of these substances in tenocytes.