Forty one people with GTPS, ranging from mild to severe (11 not seeking treatment and 10 awaiting surgery), 20 with severe hip OA, and 23 age and sex matched asymptomatic participants (ASC) were recruited from public and private hospitals, and the community. Inclusion and exclusion criteria assured mutually exclusive groups. Assessment included the Harris Hip Score (HHS), a battery of passive and resisted tests (recording reproduction and location of pain), and the single leg stance test. Statistical analyses used include Fisher exact test, ANOVA, and recursive partitioning to develop two classification trees. The first classification tree was based on an undifferentiated hip pain response and the second was based on a clearly identified lateral hip pain response.

The HHS domains of maximum walking distance and the ability to manipulate shoes and socks were the only domains to differentiate between the two symptomatic groups, (ANOVA: p=0.010 and p<0.001 respectively). Dichotomising these data resulted in OR (95% CI) of 3.47 (1.09 to 10.93)—for the ability to walk >30/60; and of 0.06 (0.00 to 0.26)—for the ability to manipulate shoes and socks, of having GTPS versus hip OA. The first classification tree resulted in a four branch tree for diagnosing GTPS, with a mean (se) sensitivity and specificity of 0.78 (0.058) and 0.28 (0.080) respectively. These branches included a positive Ober and passive to active medial rotation ratios. The second tree resulted in one branch, FABER, for diagnosing GTPS with a mean (se) sensitivity and specificity of 0.81 (0.019) and 0.82 (0.044) respectively. The single leg stance test did not differentiate between the two symptomatic groups.

Three features differentiated people with GTPS from those with hip OA without reference to our inclusion criteria. These results provide clinicians with markers to aid with the sometimes difficult diagnosis of GTPS.2 When combined with greater trochanter palpation, this combination of features is likely to be more sensitive and specific than the FABER test result. We recommend that the clinical syndrome of GTPS be defined as a history of lateral hip pain in the absence of difficulty with manipulating shoes and socks, together with an examination of findings of pain reproduction on palpation of the greater trochanter (a previously recognised sign) and lateral hip pain with a FABER test. In patients who cannot differentiate the site of their pain, multiple pathologies should be considered. For research purposes or in cases of poor response to treatment, multiple pathologies should be considered and a hip x-ray should be undertaken to exclude joint pathology.

Patients with a history of rotator cuff tendinopathy were recruited into groups defined by the treatments being undertaken and the structural integrity of the rotator cuff was assessed using ultrasound or arthroscopic diagnosis. Three groups were recruited:

Biopsies of the supraspinatus tendon were taken on the day of intervention, prior to treatment, and repeated at initial follow up 7-weeks post-intervention. These paired samples were then analysed to evaluate the tissue response to the intervention undertaken. Samples were taken under ultrasound guidance from the supraspinatus tendon. The tissue samples were wax embedded, sectioned and stained using the following markers: CD34 to identify vascular endothelial tissue; CD45 Leucocyte common antigen to identify white cells as a marker of inflammation; MIB-1 to identify proliferating cells; Active Caspase-3 to identify cells undergoing apoptosis.

Slides were imaged using a Zeiss Axio Imager M1 light microscope. Analysis used computer software to calculate the cellular density from the H&E images and the proportion of positively stained tissue from the immunohistochemistry images.

Table 1 details the composition of the study groups. The immunohistochemical results (figure 1 at the top of next page) show a comparison of tissue characteristics on the day of intervention (pre-) and 7-weeks post-intervention. A significant increase in vascularity is seen in the RCR group at 7-weeks post intervention. There is a significant increase in inflammatory cells post treatment in the SAD and RCR groups. Proliferation is significantly reduced post treatment in the GCI group. No difference was seen in apoptosis after any of the interventions.

Figure 1.

Histological analyses (*p<0.05 paired t test Pre vs Post).

Table 1.

Group Sizes

This study has shown changes in tissue characteristics in response to treatment. The results show increased vascularity in the RCR group, supporting a theory of a healing response. Both surgical groups showed increased inflammation within the tissue, which may simply reflect the early post-operative sampling time point. Perhaps the most significant finding was the reduction in proliferation within the tendon tissue in response to glucocorticoid injection supporting the theory of the negative effects of steroid treatment in tendinopathy. Further work is needed to define other biomarkers of tissue response and to investigate the tissue effects of treatment at other time points post-intervention.

In relation to a specific clinical case, a medical history review was developed: personal history, diagnosis, treatment and progress.

Asthmatic 45 year old male occasionally undergoing medical treatment with inhaled corticosteroids. Previously asymptomatic. Training athletics in the morning and handball in the afternoon. After the first 10 min of the match notices a bilateral acute pain when starting to run, showing ruptures of both Achilles tendons confirmed by MRI scan.

Treatment: surgical open-to-end suture reinforced with inverted taenia (see figure 1 below).

Development: 3 weeks immobilisation without setting foot, 3 weeks Walker boot, partial setting foot and rehabilitation, medical discharge after 6 months without complications.

Simultaneous and spontaneous rupture of bilateral Achilles tendons in patients without pathological factors is really unusual. 25% of the healthy population above 30 years of age has degenerative structural changes in the Achilles tendon that increase the risk of rupture depending on the patient's activity level.

Both percutaneous and open surgical treatments on young and active patients provide an appropriate alternative. The open surgical treatment allows the possibility of tendon reinforcement techniques and a more complete visualisation of the damage.

The postsurgical rehabilitation management is an important factor for biomechanic tendon recovery alsoallowing the restart of patient's activities as soon as possible.

Figure 1

Appearance of Achilles tendon before (left) and after (right) surgical repair.

A retrospective study was done with 12 patients with a mean age of 46.41 years, who suffered biceps distal tendon tear treated by early surgery with the two incision of Mayo technique. Rehabilitation treatment was performed and functional outcomes were assessed from the sixth month of the intervention, using the Mayo Elbow Score (MES). The range of movement was measured by manual goniometer, and the force with medical research council scale.

Two of our 12 patients were taking statin, and three of them were smokers. The time from the break until surgery was 9.5 days on average, arrested by maintaining a splint for 5 weeks. Patients needed an average of 6 weeks of rehabilitation. Functional outcome showed a mean 95.11/100 with MES, at 6 months after surgery, which was considered excellent, with a range of motion that averaged 140°±15° and a muscular balance average of 4+/5, compared with the healthy arm. The reintroduction to usual sport was 88.9% at 10 month after surgery.

Early repair of distal biceps tear followed by a rehabilitation treatment allows a good functional recovery and reintroduction to the sport.

Design: Cases series.

Setting. MVClinic Physiotherapy.

Inclusion criteria were clinically diagnosed lateral epicondylitis (based on symptoms, site of tenderness, and pain elicited with resisted active extension of the wrist in pronation and elbow extension), onset of symptoms (equal to or more than 3 months), no previous local injections (eg. cortisone), no cervicoarthrosis C5–C6, no rheumatic disorder, no history of trauma, and no signs of posterior interosseous nerve entrapment.

Sonographic assessment, pain was evaluated using a visual analogue scale (VAS), algometry, and functional status was evaluated by completion of the DASH and Cozens test and Thomsons test which were recorded at base line and at the end of treatment, at 6w and 6m post-treatment.

All patients received Electrolysis Percutaneous Intratissue (EPI)-one treatment session per week. At home, a simple programme of stretching and eccentric loading exercises to be performed on an individual basis twice every day.

No cortisone or non-steroidal anti-inflammatories were prescribed during follow-up. For pain relief only, oral paracetamol and ice therapy were used.

36 subjects were included in the study, 52.8% men (47.2% women) with a mean age of 38 years. 80.5% of subjects reached a complete response after four sessions of EPI with a VAS<2, 86.2% negative Cozens test and Thomsons test, and algometry values changed very significantly from 7.9 kg of pressure on the lateral epicondyle to 29.3 kg. DASH questionnaire showed significant changes, the mean score in the total of 36 subjects was 37.4 points, which means that there was an improvement of over 40% in functional capacity. Sonographic assessment showed change in the structure of the tendon, or hypoechoic region (long term outcomes, no short outcomes) and neovascularization (short outcomes).

The combined programme of EPI, more eccentric exercise and stretching is an effective treatment for chronic elbow lateral epicondylitis.

The main limitation is the absence of a control group to compare the results obtained with a placebo or another intervention. In scientific literature, there are no similar studies as the technique has been recently developed. The next step is to launch a pilot study to validate the results.

This novel pilot study was designed to explore the efficacy of PRP injections in the wheelchair population with biceps tendon pathology. Validated study outcomes included the Ultrasound Shoulder Pathology Rating Scale (USPRS), the Physical Examination of the Shoulder Scale (PESS) and the Visual Analogue Scale (VAS). Spinal cord injury athletes with chronic shoulder pain were recruited for this study. Members of the tetraplegic rugby and the wheelchair basketball teams at the National Rehabilitation Hospital were specifically targeted for recruitment because of the high prevalence (50%) of bicipital tendinopathy in this population. Participants in the study demonstrated AIS scores of A-D for at least 1 year, shoulder pain for at least 6 months and require the use of a manual wheelchair for the preceding year. Each participant enrolled underwent baseline analysis including USPRS, PESS, VAS and functional scores. Participants then underwent a unilateral biceps tendon sheath injection of PRP and were followed every 2 weeks to monitor VAS scores and adverse events. The study was concluded with an 8 week follow up evaluation. The hypothesis was that an ultrasound guided tendon sheath PRP injection would result in a significant change in USPRS, PESS and VAS scores over the course of the 8-week study period.

The study analysis includes eight participants who have completed the full course of treatment and analysis. Comparison of baseline and 8 week data using a non-parametric Wilcoxon Signed Ranks Test demonstrated significant change in the non-injected shoulder on USPRS score (Z=2.207, p=0.027) in PESS score (Z=2.120, p=0.034)) and in the VAS-pain score (Z=2.041, p=0.41). Repeated measure General Linear Model analysis revealed statistically significant trends in the change of pain score measured via VAS at five time points (0, 2, 4, 6, and 8 weeks) for injected arm (F=6.68, p=0.061) but not for the untreated arm. No adverse reactions were reported during the study period.

The initial pilot data from this study demonstrates a significant effect of PRP using relevant and standardised measures compared to the opposite extremity as a control. While the study sample is admittedly small, a non-parametric analysis demonstrates convincing data on the overall positive effect of PRP in the treatment of biceps tendinopathy in the spinal cord injury population. Given the study results, further investigation is warranted including a randomised control trial.

A patient controlled study in which the standardised QST protocol developed by the German Research Network on Neuropathic Pain was used. This protocol consists of seven different tests that measure 13 somatosensory parameters and can be seen as the gold standard to measure somatosensory function.

Twelve athletes with clinically diagnosed chronic patellar tendinopathy (PT) with a mean duration of 30 months (range 6–120) and 20 controls were included in the study. In two of the 13 QST parameters, namely Mechanical Pain Threshold (p<0.05) and Vibration Disappearance Threshold (p<0.5), injured athletes were significantly more sensitive for the applied stimuli. None of the athletes had signs of Dynamic Mechanical Allodynia.

Reduced mechanical pain thresholds or pinprick allodynia reflects the involvement of central sensitisation upon the myelinated (Ad-fibre) nociceptive input. From this explorative study, we conclude that sensitisation may play a prominent role in the pain experienced during and after sports activity, by patellar tendinopathy patients.

A randomised double blind, placebo-controlled clinical trial was done, comparing a 12 week programme of using a GTN patch or placebo patch in combination with eccentric squats on a decline board. Measurements were performed at baseline, 6, 12 and 24 weeks. Primary outcome measure was the VISA-P questionnaire. Secondary outcome measures were patient satisfaction and pain scores during sports. Generalised Estimated Equation was used to analyse the treatment, time and treatment x time effect. Analyses were performed following the intention-to-treat principle.

VISA-P scores for both groups improved over the study period to 75.0±16.2 and 80.7±22.1 at 24 weeks. Results showed a significant effect for time (p<0.01) but no effect for treatment x time (p=0.80). Mean VAS pain scores during sports for both groups increased over the study period to 6.6±3.0 and 7.8±3.1. Results showed a significant effect for time (p<0.01) but no effect for treatment x time (p=0.38). Patient satisfaction showed no difference between the GTN and the placebo group (p=0.25) after 24 weeks, but did show a significant difference over time (p=0.01). Three patients in the GTN group reported some rash.

Continuous topical GTN treatment in addition to an eccentric exercise programme does not improve clinical outcome compared to placebo patches and an eccentric exercise programme in patients with chronic patellar tendinopathy.

We have evaluated patellar tendons according to a routine ultrasound examination protocol for chronic painful patellar tendons/proximal patellar tendinopathy, 3 to 5 years after treatment with sclerosing injections (n=19) or arthroscopic shaving (n=25). Tendon thickness was measured and tendon structure and the amount of neovascularization was evaluated and scored, to be compared with corresponding values at baseline and at the 1 year follow-up. Self-reported pain during rest and patellar tendon loading activity, and patient satisfaction with the result of the treatment was registered on a visual analogue scale (VAS).

At the 3–5 years follow-up, preliminary results showed that tendon structure seemed to improve, and the neovascularisation was reduced, in both groups. There was a trend towards a decrease in antero-posterior thickness of the proximal part of the patellar tendon in patients treated with arthroscopic shaving, but not for tendons treated with sclerosing injections. There were no differences in VAS score at rest and during activity between the two treatment groups or in VAS score for satisfaction with treatment.

Treatment of patellar tendinopathy/jumper's knee with ultrasound and colour Doppler-guided sclerosing injections and arthroscopic shaving showed remaining good clinical results after 3–5 years for both methods. Treatment with sclerosing injections requires multiple injections with 6–8 weeks in between, but in the 3–5 years perspective seems to reach the same result in terms of ultrasound findings and self-reported pain (VAS) as treatment with the one-stage procedure arthroscopic shaving. This is in contrast to the results at 1 year follow-up where the surgical method showed better results in all evaluated variables. One remaining difference between the two treatments was that only the surgical method showed a decrease in antero-posterior thickness. In fact tendon thickness in the group treated with sclerosing injections were increased at the 1 year follow-up, while now 3–5 years after treatment the thickness seems to be back at the same level as at baseline, before treatment.

Labelling MSCs with technetium99m linked to HMPAO enabled non-invasive monitoring of cell fate in clinical cases (n=13). This revealed high initial cell loss (~75% over 24 h). Longer term labelling with a fluorescent cytoplasmic dye showed the retention of small numbers of labelled cells for up to 5 months, similar to that reported for shorter term studies.4 5

In a controlled experimental study of naturally-occurring SDFT injuries (n=12), MSC-treated tendons had greater elasticity, reduced cross-sectional area, and cellularity, improved organisational scores, and lower GAG content compared to saline-treated tendons, although not all parameters were statistically significant.

In 113 treated racehorses, the re-injury percentage was 27.4%, which was significantly less than published for racehorses treated in other ways (p<0.05 vs 56% 6; p<0.01 vs 50% 7).

These findings in a large animal model of naturally-occurring tendinopathy provide supportive evidence for the efficacy and safety for the use of MSCs for the treatment of tendinopathy in humans.

Two novel scaffolds were evaluated as biomaterials: Spidrex 543 (Oxford Biomaterials Ltd, UK), a spider-like silk fabric; and Endoform (Mesynthes, New Zealand), a decellularised ovine forestomach matrix then compared to three-dimensional (3D) collagen gels as a control and FiberWire (Athrex. Inc, USA), a polyethylene and polyester composite suture, which is currently utilised in orthopaedic surgery.

Primary human dendrocytic cells were exposed to scaffolds, with cell-surface activation markers analysed using FACS to determine scaffold immunogenicity. Attachment and growth of primary tenocytes were analysed using live-dead staining and alamar Blue fluorescence. Phenotypic retention was assessed through morphological studies, while real-time PCR was employed to evaluate cell differentiation.

FACS analysis determined that Spidrex 543, invoked a high immune response in the primary human dendrocytes, while Endoform and the 3D collagen gels provided relatively low immunogenicity. FiberWire, the synthetic suture material currently used in orthopaedic surgery produced relatively high immune activation within these cells.

Tenocytes successfully adhered to and grew on the Endoform, Spidrex 543 and within the 3D collagen gels, whereas the orthopaedic suture material proved unsuitable for cell attachment/growth. Gene analysis and morphology in the three permissible scaffolds suggest cells retain their phenotype when cultured in them.

3D culture systems support and amplify tenocyte proliferation and differentiation whilst gene expression data indicated increases of tenocyte-like markers, such as tenomodulin, scleraxis and collagen IA1

We have developed an in vitro evaluation package to identify the biocompatibility of biomaterial scaffolds- whether the materials support and promote target cell growth and have potential for use in tendon regeneration. Much time and expense can be saved by such in vitro evaluation of biomaterials prior to embarking on in vivo studies.

Sheep (n=72) had a hemitransection on the cranial side of their infraspinatus tendon (IT) midway between the bony attachment and the musculotendinous junction. Multipotent heterologous marrow-derived MSCs (30 million in 0.25 ml saline) were injected (with ultrasound guidance) into the transection site 2 (n=18) or 11 (n=18) weeks after surgery. IT were harvested from six animals in each of the resulting four groups (non operated controls (NOC); cut but no MSCs (Cut); Cut & MSCs @ 2 weeks; Cut and MSCs @ 11 weeks), at 13, 26 and 52 weeks post transection. IT were fixed, sectioned and stained with H&E (cellular and vascular pathology), picrosirius red (collagen fibre alignment) and toluidine blue (proteoglycans). Resulting sections were then scored for the above outcomes independently by two observers blinded to treatment. Other portions of tendon were snap-frozen for RNA isolation followed by real time RT-PCR using ovine specific primers for matrix and metalloproteinase genes. Normal or pathological IT explants were also harvested for co-culture for 1 or 5 days with MSCs, before and after freeze/thawing tendon explants to devitalise tendon cells. Gene expression of the MSCs from these co-cultures was measured by RT-PCR and analysed by regression modelling.

MSCs injected intralesionally at both time points, significantly ameliorated histopathological changes in stress-deprived tensile tendon 3 months after surgery (p<0.05) but only injections at 11 weeks after surgery were effective in the long-term (52 weeks, p<0.05). While MSCs modulated the gene expression profile compared to Cut, particularly at 3 months, there was little difference between tendons injected 2 and 11 weeks. Tendon extracellular matrix, pathology, the presence of live cells and time cultured, significantly and differentially altered gene expression by MSCs in vitro (figure 1), but did not suggest the MSCs were differentiating into tenocytes.

Figure 1.

Venn diagram showing genes expressed by MSCs that were significantly affected by each variable in vitro.

We have demonstrated that MSC injections can be effective in reducing surgically-induced tendon pathology and that timing of injection is critically important to the long-term benefit. The in vitro changes in MSC expression suggest that both the tenocytes and the condition of the extracellular environment determine the secretome of the injected cells, and that the MSCs are responding to feedback from their immediate environment. MSCs have potential in the development of a cellular therapy to treat tendinopathy that develops after injury.

Primary human tenocytes were isolated from hamstring tendons of healthy donors. Light and electron microscopy were used to examine a physical association between mast cells (HMC-1) and tenocytes, in vitro. Collagen gel contraction assay was used to examine the effects of mast cells on isolated tenocytes. Cell viability and proliferation was assessed by MTS assay. Gene expression was quantitated by qPCR.

HMC-1 mast cells were shown by light and electron microscopy to physically bind to primary tenocytes through adherent junctions. Immunostaining for stem cell factor (SCF), a mast cell growth factor, showed homogeneous expression of this protein on the surface of tenocytes. Additionally, qPCR showed an increase in tenocyte SCF mRNA expression in the presence of mast cells. In other experiments, both mast cells and mast cell sonicates were shown to induce tenocyte mediated contraction of collagen gel, which appeared to be driven by TGF-β1. MTS assay showed a mast cell mediated increase in tenocyte survival and proliferation.

These findings suggest that either through physical association with tenocytes and/or release of mediators, mast cells could play a role in the regulation and activation of tenocytes. Further studies are underway to investigate the molecular mechanisms of mast cell-tenocyte interactions and whether these could play a role in the pathogenesis of tendinopathy.

Twenty-four mature high-capacity running rats were studied. All rats received a collagenase injection into one Achilles tendon at baseline. After 1 week, animals were randomly divided into either a run or cage-control group. The run group ran on a treadmill at a 15° incline, 5 days/week at increasing duration and speed. Tendons were harvested at either 4 or 10 weeks after the start of the running regimen. Specimens were fixed in formalin and embedded in paraffin. H&E stained sections were evaluated using a modified Bonar scale by two blinded and independent assessors, with a third to resolve disputes.

At 4 weeks, higher levels of pathology were seen in the injected tendons than in the non-injected tendons (ANOVA: p=0.007). No side to side difference was seen at 10 weeks (ANOVA: p=0.309). There was no difference between running and non-running groups at 4 weeks (ANOVA: p=0.579) or 10 weeks (ANOVA: p=0.429). No interaction effects were seen between injection and running at 4 weeks (ANOVA: p=0.934) or 10 weeks (ANOVA: p=0.847).

In high capacity running rats, uphill treadmill running using these experimental parameters did not independently create histopathology of the Achilles tendon. Furthermore, the effect of collagenase did not have a long-term effect and was not influenced by running. Therefore, the combination of collagenase injection and uphill treadmill running does not seem to create a histological presentation similar to the degeneration seen in human Achilles tendinopathy.

13 unilateral Achilles tendinopathy patients were recruited with various times of symptoms. Both Achilles tendons were scanned using UTC. UTC captures 600 contiguous transverse images over a distance of 12 cm and renders a three-dimensional image of the tendon. Tendon structure was quantified from the insertion to the musculotendinous junction using customised software that quantifies the stability of the echopattern and allows semi-quantification of tendon structure, which has previously been matched with pathological specimens. Tendon structure was compared between the symptomatic and asymptomatic tendon using a related-samples Wilcoxon signed rank test.

No significant difference was observed for any of the four echo-types between the symptomatic and asymptomatic tendon (p=0.388, p=0.158, 0.624, p=0.824, respectively). Despite no differences being observed in the echopatterns, disorganisation within the asymptomatic group was diffusely scattered throughout the length of the tendon. Disorganisation in the symptomatic tendon was confined to focal lesions predominately characterised by echo-types representing extensive fibrillar disorganisation.

Despite the overall echopattern of the tendon not differing between the two groups, the distribution of disorganisation within the tendon differed. However, as changes in tendon structure were not confined to the symptomatic tendon, treatments should aim to improve tendon structure in both limbs to minimise the risk of developing symptoms and potential tendon rupture.

Human tendon from people undergoing gluteal tendon reconstruction or hip arthroplasty was assessed in each part of this study. Two researchers experienced in using the Bonar score systematically reviewed each domain of the Bonar score while viewing tendon sections. By consensus, the appropriate level of magnification used for each domain was determined. The need for polarisation was also reviewed. Additional clauses of pathological acellularity and avascularity were added to the third. Hyper and hypo cellularity were defined, and, modification of the vascularity and cellularity scores were confirmed. Two researchers, with a third to resolve disputes evaluated 32 sections of tendon. Each domain within the Bonar score was evaluated in each of the following areas: the area of worst collagen disruption; the area scoring the highest vascularity; and thirdly the area scoring the highest tenocyte morphology change.

A total of 84 areas of tendon were evaluated. The total Bonar score was highest in the areas of most cellular morphological (CM) changes (mean, (SD) 14.4 (1.50)) then highest collagen disruption (CD: 13.0 (2.56)), and lowest for the area of vascularity (VS) (11.6 (1.68), (regression: CD vs TM p=0.008, CM vs VS p<0.001, CD vs VS p=0.013). Our review of this method found that collagen disruption should be assessed over the entire section using x100 total magnification with polarisation. The field of view (FoV) with the highest level of disruption should be further evaluated to provide the section score.

This paper provides clarification of, and recommendations on the use of the commonly used Bonar score. Cellularity is best assessed using one FoVx100. In human tissue, hypo-cellularity ≤20 nuclei per HPF, Hyper-cellularity ≥30 nuclei per HPF. Normal=20 to 30 nuclei per HPF. Cell morphology was best assessed at x200 magnification, over four FoV. Vascularity should be assessed at x400 magnification, up to 10 FoV, and Ground substance was best assessed at x100. When evaluating a FoV, a 20% rule should be applied. That is, if 20% of the tissue can be scored at the highest level, this score is applied to the entire FoV. To provide accurate/reliable assessment, tendon sections should be viewed by a minimum, of two researchers, simultaneously, but independently with the final score decided either by consensus, or a third assessor.

These results suggest that using the area of maximum tenocyte morphological changes provides a justifiable score that is representative of the worst degree of tendinosis in the specimen. We believe our modified Bonar score provides clearer definitions of each grade and also specifies the level of magnification for each domain, producing a more robust assessment tool. Further evaluation of the Bonar score's applicability to commonly used tendinopathy laboratory models should be carried out.

Tendon specimens were collected from six participants undergoing gluteal tendon reconstruction for long standing (mean duration=41 months) GTPS, and four participants from an age-matched reference group (REF) of hip OA patients asymptomatic for GTPS. Specimens were collected using sterile technique and were stored at –80°C. RNA was isolated via laser capture micro-dissection (LCM) of areas of tendon that typified tendon rather than para-tendon or vessels within the specimen—identified using light microscopy and H&E staining. Specimens were tested using the SABiosciences array (PAHS-013). Immunohistochemistry was used to confirm the site of a subset of the expressed genes.

We report on gene regulation changes of at least five fold that were seen in the GTPS group compared to the REF group. Genes involved in extracellular matrix modelling were both up regulated (MMP7) and down regulated (MMP3). The following cell adhesion genes were up regulated: ITGAV, NCAM1, ITGAM, while ITG3 was down regulated. The following genes involved in ECM synthesis were up regulated (LAMC1, COL1A1, COL5A1, Col6A1), while ADMATS1, LAMB3, VTN were down regulated.

This paper presents a novel method of tissue specimen selection (LCM), reducing the likelihood of RNA contamination from cells other than tenocytes. Further, these results suggest that there is increased cell activity and collagen production indicating that the tendon is continuing to actively remodel despite prolonged tissue damage. This supports the role of appropriate advice regarding tendon loading and compression, exercises to strengthen the musclo-tendinous unit, and ongoing support to patients. Recovery from tendinopathy may be possible—even in longstanding cases.

Ten week old male C57Bl/6 mice (Charles River) underwent left hind (LH) needle-injury and were sacrificed after 20 weeks along with non-injured controls. Hind limbs were examined by micro CT before testing isolated Achilles tendons using the following protocol: 30 cycles of loading between 0.23 and 4.5 N; 300 s dwell at 4.5 N; 495 s dwell at 0.23 N; and a ramp to failure at 5 mm/s. Creep was calculated as the percentage change in gauge length between the first loading peak and the end of the dwell at 4.5 N. Tangent stiffness was calculated from the slope of the force/displacement ramp to failure plot over the range 40–80% of failure force. Within and between group differences were examined using paired T and exact Mann-Whitney U tests respectively.

Figure 1 shows that within injured individuals the volume of mineralisation was greater (p=0.01) in the LH compared with the right hind (RH) leg, and within non-injured individuals there was no difference between hind limbs (p=0.4). The volume of mineralisation was greater in the LH and RH of injured individuals compared with the respective limbs in non-injured individuals (both p=0.017). The mean failure force was lower (14.8±1.7 vs 16.7±0.7 N) and stiffness (22.9±2.7 vs 19.6±1.5N/mm) and creep (1.9±0.3 vs 3.1±1.2%) were higher in LH compared with RH limbs in six injured individuals (all P≤0.048). Differences between the mean values for seven LH limbs from injured (I) and three control individuals were not statistically significant for failure force (I=1.2 N lower, p=0.28), stiffness (I=3.5 N/mm higher, p=0.067) and creep (I=0.4% higher, p=0.067). All tendons failed close to the insertion except one injured tendon which failed partly in the mid substance and at the insertion.

Figure 1.

Mean volume (mm³) of peri-Achilles tendon mineralisation in injured (I, n=7) and control (C, n=3) animals.

Unilateral needle-injury accelerated tendon mineralisation bilaterally. In humans, tendon mineralisation and other orthopaedic diseases often occur bilaterally, which may partly relate to interaction between contralateral limbs such as by altered loading of a non-injured limb, signal circulation or bilateral neurological effects of injury. The model presented here is therefore an excellent one to study this phenomenon. Needle-injured mineralised tendons were weaker (consistent with human clinical data), but stiffer and showed less creep than contralateral controls. This suggests that in patients, tendon mineralisation may alter limb function unless muscular adaptation occurs. Most injured and control tendons failed close to the insertion, in contrast to a report of similar tests in which most tendons from adult C57Bl/6J mice failed in the mid substance,2 perhaps explained by potential sub strain differences.

9 partially torn supraspinatus tendons and matched intact subscapularis tendons were biopsied and compared to 10 reference subscapularis tendon samples. Immunohistochemistry was used to assess apoptotic cells (activated caspase-3; Asp175), proliferation (Ki67) and p53 (M7001), a key protein involved in regulating cell death. The Bonar scale was used to evaluate tendon degeneration.

The partially torn supraspinatus tendons and matched subscapularis tendons demonstrated a significant increase in the density of apoptotic cells and p53 expression. The Bonar score revealed significant tendon degeneration in the partially torn supraspinatus tendon compared to both matched and reference subscapularis tendon. The number of proliferating tendon cells was higher in the partially torn supraspinatus than in the matched or reference subscapularis tendons.

The presence of increased apoptosis and p53 in partial-thickness tears of the supraspinatus tendon is accompanied by features of both degeneration as well as ongoing repair. Apoptosis may be a relatively early feature in the continuum of rotator cuff tendinopathy.

Participants were grouped using ultrasound or arthroscopic diagnosis of cuff integrity and subdivided by the treatments being undertaken.

Samples were taken under ultrasound guidance from the supraspinatus tendon. The biopsies were obtained in clinic under local anaesthetic for the injection group and in the operating theatre for the surgical and control groups. The tissue samples were wax embedded, sectioned and stained using the following markers: H&E to assess cellularity; CD34 to identify vascular endothelial tissue; CD45 Leucocyte common antigen to identify white cells as a marker of inflammation; MIB-1 to identify proliferating cells; Active Caspase-3 to identify cells undergoing apoptosis.

Slides were imaged using a Zeiss Axio Imager M1 light microscope. Analysis used computer software to calculate the cellular density from the H&E images and the proportion of positively stained tissue from the immunohistochemistry images.

Table 1 details the composition of the study groups. The quantitative histological analyses (figure 1) demonstrate a significant reduction in vascularity and cell proliferation in line with progression of pathology. There was no significant change in cellularity. A significant increase in inflammatory cells and apoptotic cells was seen in early tendinopathy represented by the injection group compared to controls.

Figure 1.

Histological analyses (*p<0.05 t-test vs control group).

Table 1.

Group sizes and mean age

This study has demonstrated significant changes in tissue characteristics across the progressive stages of rotator cuff pathology from a unique group of tissue samples obtained consistently from a focal area of the supraspinatus tendon in normal and tendinopathic tissue using a novel ultrasound guided biopsy method. The results suggest an early inflammatory component to the condition in patients with clinical signs of impingement but without tearing of the tendon. As the tendinopathy progresses to require subacromial decompression and eventually rotator cuff repair due to full thickness tearing of the supraspinatus tendon, the viability and healing potential of the tissue deteriorates significantly with reduced vascularity and proliferative activity within the tendon tissue.

The ApoE-KO mice are fed a high fat or regular diet at 7 weeks of age, and sacrificed at 0, 15, and 30 weeks. For collagen density and organisation, tendon tissue will be viewed using second harmonic generation microscopy to determine collagen density and organisation. Tendons will be systematically scanned, and collagen density will be determined and compared among different study groups. Lipid deposition in Achilles tendon will be observed with oil red O and filipin staining. Tissue sections will be viewed and photographed with brightfield, polarisation, and fluorescence microscopy. Filipin dye will be excited with epiillumination and viewed through a 510-nm barrier filter. Ultrasound imaging will be used to analyse patellar tendon cross-sectional area (ie, tendon thickening, an indicator of tendon pathology). The effect of dyslipidemia on tendon biomechanics will be determined by testing the tendon to failure at 0.003 mm/s in a Bose ElectroForce BioDynamic test instrument. Local strain will be measured and tendon stiffness calculated.

Tendinopathy tendon in an H&E stained tissue section is expected to show disorganised collagen architecture with high cellularity of rounded tenocytes (as compared to parallel, longitudinal architecture with scattered elongated tenocytes of normal tendons).4 Tissue sections of Achilles tendon is expected to have wavy, discrete, band-like deposits of green filipin staining. Oil red O staining is to be observed intracellularly and extracellularly.5 If significant, these results will provide the first insights into the biology underlying dyslipidemia-induced tendinopathy, and could have direct impact on clinical care and preventive strategies.

Analysis of total and specific GAGs using a DiMethyl Methylene Blue histochemical technique and immuno-histological technique with antibodies against Dermatan Sulfate, Chondroitin Sulfate, Heparan Sulfate and proteoglycans (PG) (decorin, versican and aggrecan) respectively were performed on normal and pathological tendon sections from rat supraspinatus and human patellar tendons.

As observed in rat overused supraspinatus tendon, total GAGs as well as Dermatan and Chondroitin sulfate were increased in human pathological patellar tendon. Correlatively, PGs such as decorin, and above all versican and aggrecan were also enhanced. Amounts of GAGs and aggrecan found in tendons changed with the Visa score of patellar tendons. A correlation was established between VISA score and the amount of GAGs. This correlation allowed us to verify the correct sampling of patient tendons and was predictive for the extent of pathology of unclassified tendon samples.

This study underscores the importance of excessive GAGs in relation to tendon pain and function. Accurate GAG assessment would represent a help in establishing a reliable diagnostic of patellar tendinopathy as a complement of the Visa score. This knowledge may be useful in stimulating the development of more sensitive imaging modalities capable of detecting early changes in the composition of tendon extracellular matrix.

13 patients diagnosed with calcifying tendinitis of the shoulder were treated using an ultrasound and radiology study. They underwent the Constant and Oxford questionnaire to assess shoulder pain and function. The technique employed was ultrasound-guided percutaneous aspiration. Two groups were formed: group 1 with the aspirated patients; group 2 with patients in which calcification was fragmented. The patients were monitored after 1 month and 3 months from commencement of treatment.

The treated patients consisted of seven men and six women, aged between 40 and 57. In the functional assessment of the shoulder prior to treatment and 3 months following treatment, the difference in the Constant score was 58.69 points and 17.38 points in the Oxford score. The differences were statistically significant (p=0.001) for both scores. In the clinical assessment and in the decrease of calcification, better results are obtained in the group that had the calcium deposits aspirated, compared to the other group where calcification was fragmented.

Patients that had calcification removed had better clinical results than patients that did not. Ultrasound-guided percutaneous aspiration is a good treatment.

PG content (toluidine blue staining) was scored in regional SDFT (12 regions) sections from formalin-fixed tissue harvested from animals (n=6 per group) 6 weeks after sham or mid-tendon lateral hemitransection surgery at the midmetacarpus. Aggrecan (ACAN), versican (VCAN), ADAMTS4, ADAMTS5 and TIMP1, 2 & 3 gene expression was measured by real time RT-PCR on samples from the same regions. Mixed regression models (clustered by animal and region) were fitted to log-transformed expression data to determine whether surgery or any of the positional (side or proximity to cut/carpus/MCP) covariates was a significant factor.

Both PG histological scoring and ACAN expression (p=0.006) were higher with distance from the midmetacarpus before surgery but not afterwards, when ACAN expression increased (p<0.001), particularly in the regions around the surgery site, and PG score increased in all but one region (figure 1). VCAN was evenly expressed in control SDFT but increased upon surgery (p<0.001) to be significantly higher on the lateral side (p=0.002) and towards the carpus (p=0.010). ADAMTS4 was expressed significantly more on the lateral side (p<0.001) and towards the carpus (p<0.001) both before and after surgery however decreased with surgery (p<0.001) significantly more nearer the lesion (p<0.001). ADAMTS5 expression was not significantly altered by transection (p=0.29). Surgery increased TIMP1 (p=0.019), decreased TIMP3 (p<0.001) and had no significant effect on TIMP2 (p=0.36) expression. Only TIMP1 varied by region, being higher on the lateral side after surgery (p<0.001).

Figure 1.

Map of proteoglycan scores of regional histological tendon sections from horses with and without a lateral SDFT hemitransection 6 weeks earlier. Region is shaded if difference between sham (light bars) and cut (dark bars) is significant.

By 6 weeks, a midtendon injury caused pathology with increased PG throughout the full length of the tendon. Increased ACAN and VCAN expression did not account for all regional changes; decreased ADAMTS4 expression suggested turnover of existing PGs was also impaired. The widespread chondroid metaplasia following a focal injury will significantly affect the tendon material properties and may, in part, explain the poor long-term prognosis.

Design: Controlled laboratory study.

Department of Veterinary. University Complutense of Madrid-Spain.

Twenty-four male Sprague Dawley adult rats were included in this experiment, weighing 190–240 g. In all cases, healthy Achilles tendons were treated. In the intervention group (n=18), one Achilles tendon was treated with dry needling, and the other was treated with electrolysis percutaneous intratissue. In the control animals (n=6) no intervention was carried out. Twenty four total tendons were treated with dry needling, and 24 tendons with electrolysis percutaneous intratissue, and 12 tendons were the control animals. In the experimental animals, one Achilles tendon was treated with dry needling (two impacts), and the other was treated with EPI 4 mA, 4 segs. and 2 impacts. Animals were euthanized after 0, 1, 3, 8, 14 and 21days after intervention by CO₂ asphyxiation. Muscle–Achilles tendon–bone units were harvested by transection of the middle part of the gastrocnemius muscle and of the calcaneus. Tendons were harvested and stained using E&H and scored semi-quantitatively for total white blood cells (WBCs), mononuclear cells (macrophages and lymphocytes), polymorphonuclear cells (PMNs), vascularity, fiber structure, and fibrosis.

After intervention the macroscopic findings (0 days) inflammatory response and haemorrhage were higher in EPI group versus dry needling. There is no significant difference in the cellularity regardless of the intervention types (dry needling vs EPI) at 0 days after intratendinous intervention. Compared with Dry Needling, Electrolysis Percutaneous Intratissue causes a significantly greater acute inflammatory response at 1 and 3 days after intervention and focal areas of scar tissue. Compared with findings in control specimens, histological analysis of EPI showed a marked inflammatory infiltrate. Histological examination of the repair tendon tissue showed that by 14 days delivery of EPI led to the formation of well-organised, tendinous tissue with large collagen fibres.

Electrolysis Percutaneous Intratissue can stimulate the tendon biology, initiate an inflammatory response and promote wound healing in normal tendon in rats.

A limitation of the present study is the use of rat Achilles tendon, which does not accurately reflect human Achilles tendon. Future investigations are necessary to apply these findings to the clinical setting.

Rabbit Achilles tendons will be subjected to varying loading regimens using the in-vivo Backman model. After set periods of exercise, microdialysis and blood samples will be taken and analysed for genes involved in degradation of tendons. At the same intervals, ultrasound images will be taken to track changes in the cross sectional area of the tendon. After the end of the full exercise period, the tendon tissue will be examined for characteristic degradative changes using microscopy.

It is expected that the exercise regimen will lead to significant changes in gene expression in the tendon.1 Blood and microdialysis samples are expected to show significant changes in for example, collagen type I and III, matrix metalloproteinases (MMPs), tissue inhibitors for MMPs (TIMPs), and other genes involved.2 It is expected that the tissue will exhibit characteristic morphological changes seen in degradative tendon tissue, for example, rounded nuclei of tenocytes and a looser, kinked pattern of the collagen fibrils.3

Treatment for tendinopathies in workers can be a long and costly process which is not always successful, due to the degenerative nature of chronic tendinopathy. Detecting the early stages of tendinopathy could allow for the possibility of interventions to decrease or prevent tendon pain and/or rupture, and reduce healthcare and insurance costs.

Total mRNA isolated from ~100mg tissue samples of normal (n=9) and pathologic (n=12) tendon was assayed by relative quantitative RT-PCR for MMP (-1, -2, -3, -9, and -13), ADAMTS (-1, -4, -5), and TIMP (-1, -2, -3, and -4), and normalised to GAPDH.

Expression of mRNA for MMP-9 and TIMP-1 was significantly up-regulated in pathologic tendons (p=0.019 and p=0.013, respectively). A trend toward a down-regulation of expression of MMP-3 was observed in pathologic tendons (p=0.06). There were no significant changes in ADAMTS-1, -4, or -5 gene expressions.

These results suggest that the elevated expression of MMP-9 and TIMP-1 genes is likely to reflect the changes in collagen metabolism in pathologic tendons. However, these results also suggest that the proteolysis of proteoglycans in the pathologic tendons is not likely to be affected at the gene expression level of proteinases and their inhibitors. These observations are consistent with others, who showed no difference in the expression of ADAMTS-1, -4, and -5 genes between human Achilles tendons with chronic pain and normal tendons.2 3 Therefore, it is likely that proteoglycan catabolism is elevated by the activation of ADAMTSs and possibly MMPs and not by increased gene expression. This activation may be driven by growth factors and cytokines such as IL-1α, TGF-β and TNF-α, which are shown to be increased in overuse tendinopathy. However, the details of the mechanisms of these regulatory processes warrant further investigation.

Six high level jumping athletes with chronic painful PT/JK completed a 6-month treatment/training programme using eccentric exercises and electrical stimulation. The protocol was done12 weeks in the winter pre-season and 10 weeks in the summer pre-season, for all together 36 months. Pain during patellar tendon loading activity was evaluated on a VAS, before the first session and then every 6 months.

The VAS average fell significantly when the initial measurement is compared with those at 18, 24 and 48 months (p<0.01). There were no significant differences between the other comparisons, although they always improved when the protocol was followed and worsened following interruption of the latter (p>0.05).

In a small group of high level jumping athletes with chronic painful PT/JK, eccentric exercises combined with electrical stimulation showed promising clinical results with significant pain reduction during tendon loading activity.

Human Achilles tenocytes were grown as primary cultures and used for experiment at passage 3–5. All experiments were performed in serum-starved conditions. Cell viability (crystal violet), TUNEL-staining, and cytotoxicity assay (measuring lactate dehydrogenase (LDH)) were used to evaluate the endpoint effect of Anti-Fas alone or together with SP and/or a specific NK-1 R inhibitor. Immunocytochemistry, qPCR, and Western Blot were used to determine the pathways of Anti-Fas induced apoptosis and the specific inhibitory effect of SP.

The majority of the tenocytes expressed FasR. The LDH assay demonstrated that Anti-Fas treatment results in a time- and dose-dependent release of LDH, and that SP dose-dependently reduces the Anti-Fas induced release of LDH. In parallel, the same trend was seen for the TUNEL assay, that is, SP reduced Anti-Fas induced apoptosis via a NK-1 R specific pathway. In addition it was shown that SP reduced the Anti-Fas induced decrease in cell viability. mRNA and/or protein analysis confirmed that the Anti-Fas induced activation of caspase-8, caspase-3, BID, BAX, and PARP were all down-regulated when SP was included, and that this SP effect was mediated through a NK-1 R specific pathway (for PARP and caspase-3, see figure 1). SP treatment resulted in activation of Akt, and by inhibiting Akt the anti-apoptotic effect of SP was confirmed to be, at least partly, induced through an Akt-dependent pathway.

Figure 1.

Cleavage of PARP and caspase-3 after Anti-Fas treatment alone or together with SP and/or the NK-1 R inhibitor illustrating the anti-apoptotic effect of SP. Pan-caspase inhibitor zVAD confirms a caspase dependent cleavage of PARP.

We show that SP reduces Anti-Fas induced apoptosis in human tenocytes and that this anti-apoptotic effect of SP is mediated through the NK-1 R and an Akt pathway. Considering previous results that SP has a proliferative effect on tenocytes, the present study identifies SP as a potent regulator of cell-turnover in tendinosis tissue, capable of stimulating hypercellularity through different mechanisms. The fact that the FasR is abundantly expressed in tenocytes and that a possible source of the Fas ligand in tendinosis is the inflammatory infiltrated cells in the paratendon, makes it possible that the excessive apoptosis seen in tendinosis is partly explained by FasR stimulation. Most interestingly, as tenocytes are known to endogenously produce SP and express the NK-1 R, it is possible that SP in an autocrine loop rescues cells from Anti-Fas induced apoptosis, via Akt stimulation, thus contributing to tenocyte hypercellularity in tendinosis.

Human Achilles tenocytes were seeded in cell culture plates and incubated in serum-starved conditions. The cells were pre-treated with the EGFR inhibitor AG1478, the matrix metalloproteinase (MMP) inhibitor GM6001 or the mAChR antagonist atropine. The cells were then stimulated with ACh (10^–6 M) or the vehicle. To determine the levels of phospho-ERK1/2 and phospho-EGFR, Western blot analysis was performed. 5-Bromo-2'-deoxy-uridine (BrdU) and crystal violet staining were used to assess cell proliferation and cell viability, respectively.

The primary human tendon cells in culture expressed enzymes related to ACh synthesis (choline acetyltransferase and vesicular acetylcholine transporter), along with vimentin and tenomodulin, which confirm the tenocyte phenotype. The cells also expressed the M₂R. By administering exogenous ACh, the tenocytes were stimulated to significantly proliferate and increase in viability. In addition, Western blot showed that ACh stimulation resulted in increased phosphorylation of both EGFR and ERK1/2. When the cells were exposed to atropine, or the EGFR-blocking substance, the proliferative effect of ACh decreased. Simultaneously, the increase in ERK1/2 phosphorylation induced by incubation with ACh was effectively blocked in the presence of the mAChR antagonist atropine. Inhibition of either EGFR or MMP with specific blockers reduced the phosphorylation of ERK1/2.

Based on the results of the present study, as well as from previously established studies, we propose that human tenocytes, with their innate ability to produce ACh, increase ACh production during tendinosis development. Via an autocrine loop, the ACh produced by tenocytes stimulates mAChRs on the cell surface, thereby activating MMPs to cleave a cell surface-associated EGFR ligand. The ligand then binds to EGFR which in turn after activation increases ERK1/2 phosphorylation, leading to the increased cell proliferation and hypercellularity as seen in tendinosis (figure 1). In an early stage of tendinosis, hypercellularity might be a part of a healing or adaptive response, but in the chronic stage excessive tenocyte proliferation could be detrimental to tendon structure and function. The non-neuronal cholinergic system of tendon tissue is thus a possible target for future modulation of these processes in tendinosis.

Figure 1.

Schematic drawing of proposed cellular pathways involved in ACh-induced proliferation of human tendon cells. ACh stimulates membrane bound muscarinic ACh receptors (mAChRs) that in turn activate matrix metalloproteinases (MMPs) to cleave a cell surface-associated EGFR ligand. The ligand then binds to EGFR which in turn increases cell proliferation through phosphorylation of the mitogen-activated protein kinases ERK1/2.

A thorough search strategy including three electronic databases (Medline—via Ovid, PubMed, and Scopus) and references list were searched to February 2012 for English language papers relating to widespread manifestations in unilateral tendinopathy when compared to healthy controls. Two independent investigators assessed the quality of the included papers using the Epidemiology Appraisal Instrument.3 Data relating to population and methodology as well as the mean and SD for the outcomes of pressure pain threshold (PPT), cold pain threshold (CPT), heat pain threshold (HPT), grip strength (GS), reaction time (RT) and speed of movement (SoM) were extracted. Point estimates of effect for pooled data were calculated by a meta-analysis of differences between non-affected sites in those with unilateral tendinopathy compared to control participants.

Overall, 5420 studies were identified from the search strategy, with 248 extracted for a detailed analysis and a total of 25 included within the review. Of the 25 included studies, there were 3 animal studies, 18 lateral epicondylalgia (LE), 2 patella tendinopathy, 1 Achilles tendinopathy, and 1 rotator cuff tendinopathy. Only LE had multiple studies that could be subjected to meta-analyses, with six studying PPT, three HPT and CPT, and two RT and SoM. Comparing the non-affected side of unilateral tendinopathy with the non-dominant or left side in healthy controls, mean differences were significantly lower for PPT (–144.34 kPa; 95% CI CI –169.52 to –119.16, p<0.001), HPT (1.13°C; 95% CI –1.83 to –0.44, p=0.001), and SoM (–20.71 cm/s; 95% CI –27.47 to –13.95, p<0.001), whereas it was significantly higher for CPT (3.09°C; 95% CI 1.80 to 4.38, p<0.001) and RT (35.08 ms; 95% CI 28.49 to 41.67, p<0.001). GS was significantly reduced (–21.43 N; 95% CI; –29.70 to –13.16; p<0.001), however there was significant heterogeneity (p<0.001), requiring caution in interpreting this result.

This systematic review and meta-analyses demonstrates widespread manifestations in unilateral tendinopathy, mainly from studies of LE and requiring evaluation for tendinopathy at other sites. These results are concordant with evidence of bilateral deficits in other unilateral musculoskeletal conditions (eg, carpal tunnel syndrome,4 unilateral wrist pain5). It is not possible to determine if these deficits preceded or were a consequence of the unilateral condition. In any event, the presence of widespread changes in measures of pain and sensorimotor function in human studies imply that there are abnormal central nervous system processing. We propose that further study of these widespread changes might lead to better outcomes through improved management strategies.

By using Flexcell Tension Systems, the isolated tendon cells from human hamstring tendons (excess ACL autograft material) were exposed to cyclic tension (1 Hz frequency and 10% strain). RNA samples were isolated at different time points and gene expression was evaluated by qPCR and qPCR array. Zymography assay was also conducted in order to measure the activity of MMP-2 in the supernatant of tendon cell culture.

Initial experiments show that cyclic strain of two-dimensional primary tenocyte cell cultures (1 Hz) promotes increased expression of VEGF, bFGF, Cox-2 and IL-6 genes, and increased activity of MMP-2. But, by increasing the time course (~after 4 h), bFGF, Cox-2 and VEGF are progressively downregulated. Our preliminary results of qPCR array for angiogenic profiling of tendon cells also led to the discovery of other genes (ANGPTL4, FGF-1, TGFα, VEGF-C, PROK2 and SPHK1) that may respond to tensile loading following a similar pattern.

It seems that the early response of the tendon cell to overuse tensile loading leads to upregulation of some angiogenic factors which may play an important role in tissue homeostasis following periods of overuse.

Patients attending our shoulder clinic for treatment of traumatic shoulder instability or rotator cuff pathology were recruited to the study and tissue samples were obtained at the time of outpatient or surgical treatment. Participants were categorised by age into six groups: under 35, 35–44, 45–54, 55–64, 65–74 and 75 years and over.

Samples were taken under ultrasound guidance from the supraspinatus tendon. The biopsies were obtained in clinic under local anaesthetic for the injection group and in the operating theatre for the surgical and control groups. The tissue samples were wax embedded, sectioned and stained using the following markers: H&E to assess cellularity; CD34 to identify vascular endothelial tissue; MIB-1 to identify proliferating cells; Active Caspase-3 to identify cells undergoing apoptosis; SIRT-1 as a marker of ageing.

Table 1 details the composition of the age groups. The immuno histochemical results (figure 1) show a comparison of tissue characteristics evaluated across the spectrum of age. No significant change in cellularity was seen between the groups. Vascularity (CD34) of the supraspinatus tissue showed a significant reduction with age, showing a rapid decline in vascularity from 55 years of age onwards. A similar pattern of expression was seen for proliferation (MIB-1) with the major decline in proliferative activity occurring between 55 and 65 years. Cellular apoptosis (Active Caspase-3) showed a decline in the older age groups although this only reached significance in the 65–74 year old age group. SIRT-1 as a potential marker of tissue ageing showed a declining trend across the age groups with significant reduction in expression seen in the two oldest age groups.

Figure 1.

Histological analyses (*p<0.05 t-test vs<35 years age group)).

Table 1.

Group Sizes

The results demonstrate significant changes in several major features of tissue activity and viability within the supraspinatus tendon as age increases. Once age reached 55 years and over, the tissue demonstrated significant reductions in cellular activity and potential viability matching with the peak age of onset of rotator cuff pathology. SIRT-1 showed a constant gradual decline in expression as age increased, in keeping with the existing theories that reduction of SIRT-1 activity may be associated with cell senescence and ageing.

The study was limited by the recruitment of tissue samples from a population attending for hospital treatment. The results may include some bias associated with pathological tissue changes unrelated to the patients' age. Despite this limitation, however, this work has shown a clear and significant pattern of tissue change associated with increasing age in the population studied and will lead to future work employing similar methods to investigate the tissue changes seen in a healthy ageing population.

Patellar tendons from 1-year-old (n=8) and 3-year-old (n=6) female New Zealand White rabbits underwent RT-qPCR using rabbit specific primers for MMPs (MMP-1, MMP-3, MMP-13) and TIMPs (TIMP-1, TIMP-2, TIMP-3), and the housekeeping gene 18S. Data were compared using Mann Whitney U tests.

Comparing patellar tendons from 3-year-old to 1-year-old rabbits, the expression of MMP-1, MMP-3 and MMP-13 did not change with aging. The expression of TIMP-2 was decreased comparing patellar tendons from 3-year-old to 1-year-old rabbits (p=0.02; figure 1). TIMP-1 and TIMP-3 expression were not affected by aging.

Figure 1.

MMP and TIMP Expression in Patellar Tendons from 1-year-old and 3-year-old rabbits. Expression of TIMP-2 was decreased comparing patellar tendons from 3-year-old to 1-year-old rabbits (p=0.02).

Aging significantly decreased TIMP-2 expression in patellar tendon with no changes in the other TIMPs and MMPs investigated. This suggests a change in the balance of MMP/TIMP expression towards degradation in tendon with aging, or a significant shift in the MMP-independent activities of TIMP-2.3 In human skin, TIMP-2 expression was decreased with aging.2 Despite no change in TIMP-2 expression in degenerated human patellar4 and Achilles1 tendons compared to normal tendons, TIMP-2 expression was decreased in ruptured human Achilles1 and rotator cuff5 tendons compared to normal tendons.

A total of 358 unaffected control (CON) participants (159 South Africa (SA CON) and 199 Australia (AUS CON)) and 166 affected TEN participants (87 SA TEN and 79 AUS TEN) were genotyped for four variants (CASP8 (rs384129), CASP8 (rs1045485), NOS3 (rs1799983) and NOS2 (rs2779249)). Logistic regression was used to derive risk models for TEN and a receiver operator characteristic (ROC) curve was plotted to determine the effectiveness of the models to capture TEN risk.

An independent association of CASP8_rs1045485 and CASP8_rs3834129, together with their haplotype was observed with TEN risk. The optimal risk model identified from the study included the two CASP8 genetic loci investigated (CASP8_rs384129 and CASP8_rs1045485) together with sex to capture TEN risk in both SA and AUS participants collectively.

These findings further implicate the apoptosis signalling cascade as one of the important biological pathways involved in the development of Achilles tendinopathy.

Anabolic and catabolic biochemical analyses were performed on supraspinatus tendons from male Sprague-Dawley rats subjected to daily downhill treadmill running and control rats. Transcripts were measured by semi-quantitative RT-PCR and proteins determined by Western Blot. Total GAGs (glycosaminoglycans) were quantified using a DiMethyl Methylene blue (DMMB) based assay and specific amounts of Chondroïtin Sulfate (CS), Dermatan Sulfate (DS) and Heparan Sulfate (HS) were determined by DMMB assay after combined pre-treatments of GAG extracts with nitrous acid and/or chondroitinase B. Immunohistochemistry on tendon sections allowed localising total GAGs by DMMB staining or specific PGs (proteoglycans) and GAGs with antibodies. Gelatinase activity of metalloproteinases (MMPs) was assayed by zymography and MMP inhibitors TIMP-1, TIMP-2 and TIMP-3 were detected with reverse gelatin zymography. MMP-2 and EMMPRIN/CD147 were detected in situ by immunolabelling. Inflammatory status was studied using a cytokine array and by immunodetection of pro-inflammatory an anti-inflammatory macrophages.

After as soon as 2 weeks of tendon overuse, anabolic studies have shown collagen quantitative and qualitative alterations, increases in specific PGs and GAGs including aggrecan and CS, associated with an increase in the chondrogenic transcription factor sox9. These results proved that a precocious shift towards fibrocartilage occurs in the pure fibrous median zone of the tendon.

Results also suggested that the cytokine HARP (Heparin Affine Regulatory Peptide) was implicated in this chondroid phenotypic change. In a catabolic study, MMP-2 and MMP-14/MT1-MMP appeared to be the sole enzyme candidates, among several MMPs tested, responsible for the observed matrix remodelling at 2 weeks. Whereas it appeared that remodelling events were not associated with inflammation in overused tendon, results suggested that the MMPs inducer EMMPRIN/CD147, which increased at 2 weeks of overuse and co-localized with MMP-2, is involved in MMP-14/MT1-MMP and MMP-2 up-regulation.

This is the first report which shows specific GAGs (CS, DS, HS), together with PGs (decorin, versican, aggrecan), proteins alterations and localisation, complete with activation of specific MMPs and cytokines in early tendon overuse. These anabolic and catabolic alterations may temporarily interfere with the tendon's tensile load-bearing capacity, which could lead to more deleterious damage. Anticipated detection of these early events, some of which may be reversible, could help to develop injury prevention strategies.

Physiotherapy clinicians in British Columbia requested evidence-informed guidance on the management of tendinopathy. To address this need, the provincial Physical Therapy Knowledge Broker assembled a team of researchers, educators and expert clinicians with the mandate to develop, disseminate and implement a toolkit of decision aids to guide clinical decision-making for Achilles Tendinopathy.

The process to develop the toolkit involved the following components: (1) identification of the purpose and scope of the project (2) agreement on the processes for selection of content and format (3) creation of a mechanism for resolution of conflicting opinion (4) an iterative feedback process with stakeholders and (4) the incorporation of concepts and strategies from the knowledge translation and implementation science literature to support the stages of knowledge synthesis, dissemination and implementation.1^–4

The ‘Tendinopathy Toolkit’ included: (1) a tabulated summary of the evidence for manual therapy, exercise, low level laser therapy, ultrasound, extracorporeal shock wave therapy, iontophoresis using dexamethasone, taping, orthotics, night splints and braces, heel raise inserts, needling techniques, and the appropriate outcome measures for this population (targeted ‘take home messages’ and clinical implications for each were also included); (2) an algorithm to guide the sequence of interventions; (3) and appendices including (a) exercise programmes (b) low level laser dosage calculation (c) tabulated details for each article reviewed and (d) a review of common medical interventions.

The second phase of the initiative—utilization of strategies to enhance implementation and uptake of the toolkit—is currently being undertaken.

Clinicians want to provide evidence-informed management of tendinopathy but many struggle with accessing, appraising and synthesising the vast array of literature available on this topic. This KT initiative highlights the need for, challenges associated with, evidence-informed process for and positive response to the development of decision aids synthesising the current evidence to guide clinical management of this patient population.

A 5-year prospective cohort study among elite volleyball players, aged 16–18 was performed. Jump tests were done on a portable force plate at the time of inclusion and semi-annually. Jumper's knee was diagnosed based on a standardised clinical examination.

150 students (68 males and 82 females) were included and 28 developed jumper's knee (22 males and 6 females). At the time of inclusion, male athletes who went on to develop jumper's knee had significantly better results in CMJ (38.0±5.8 cm) compared to asymptomatic males(34.6±5.5 cm, p=0.03), while no difference was detected in standing jump (SJ: jumper's knee: 30.3±7.4 cm, asymptomatic: 28.1±6.1 cm, p=0.23). In a multivariate logistic regression analysis corrected for gender and previous volleyball training, the OR was 2.09 (1.03–4.25) per cm difference in CMJ at the time of inclusion. Our results did not reveal any significant differences in the change in jumping ability between the groups, although both groups improved their jump performance.

Volleyball players with a natural ability for jumping high are at an increased risk for developing jumper's knee.

A 33-year-old male amateur soccer player (176 cm, 78 kg BMI=25.2), presented to the clinic reporting 4 months of left Achilles pain, which started for the first time after 10 days of immobilisation following a gastrocnemius MTJ tear. He reported antibiotics intake 4 days before injury due to dental problems. The patient was unable to stand on the affected leg, had ankle ROM limitation (dorsiflexion=90°), gait alterations, 1 h of morning stiffness, and constant pain and difficulty with daily activities, with a VISA-A score of 8/100 and a SF-36 outcome of 40.18%, revealing high limitations in physical health measures. Imaging diagnosis (MRI and colour Doppler ultrasound) revealed a severe degenerative mid-portion Achilles tendinopathy, with a thickening of the affected tendon (143 mm) compared to the asymptomatic tendon (65 mm), showing severe neovascularisation, matrix disorganisation and hypoechoic areas. Blood analysis revealed no significant results in cholesterol (180 mg/dl) and glucose levels (77 mg/dl). Previous NSAIDs and physiotherapy (electrotherapy and manual therapy) had failed.

The patient was managed with a conservative treatment programme, divided into 4 main areas: 1. Orthotics (4 cm of heel raise); 2. Medical treatment (ibuprofen post-exercise and a single methylprednisolone injection in paratenon at the beginning); 3. An intensive exercise programme (consisting of a progression from isometric to concentric then eccentric strengthening, combined with electrostimulation (ES)); and 4. Functional re-training and general health measures (aerobic exercise and weight loss). Follow-up measures were taken over 1 year, recording SF-36 results at the beginning and end, VISA-A score once a month, and colour Doppler ultrasound examination every 6 weeks. Progression criteria for exercise were tendon pain and morning stiffness.

The patient reported a marked improvement in pain and function in the first 4 weeks of treatment (VISA-A=65), that consisted of isometric and concentric exercises, progressively adding external load, cycling, ES and stretching 3 times/week. Eccentric exercises were started in week 6, stretch-shorten cycle exercises in week 9, and he was able to run 14 weeks after the beginning of treatment (VISA-A=75). From then, the programme was modified once a week until he was able to play soccer in month 7 (VISA-A=100). He recovered full ankle ROM after 3 months, and had some minutes of morning stiffness until month 6. Colour Doppler ultrasound showed absence of neovascularisation after 12 weeks, and a progressive reduction of hypoechoic areas and a better fibre alignment was seen. One year later the tendon remained thickened, but had decreased from 143 to 125 mm (the paratenon was the most thickened structure), and SF-36 outcome also improved from 40.18% to 84.06%. BMI also decreased from 25.2 to 22.9.

A progressive programme of exercises focused on tendon strengthening and recover of musculotendinous function was effective in the treatment of a severe degenerative Achilles tendinopathy. Medical and orthotic treatment might be important at the beginning to reduce pain, and causative factors such as antibiotics or previous immobilisation should be taken into account when designing a programme of exercises. Tendon structure recovered and was completely functional after 7 months, despite the tendon remaining thickened. In a severe degenerative tendinopathy like this, surgical treatment could be an option to restore tendon structure, but there are risks that should be taken into account. However, as shown in this case, exercise remains the most powerful stimuli for tendon function recover.

A prospective study was performed between January and December 2011 involving 23 patients, all soccer players diagnosed with patellar tendinopathy and referred to the Physiotherapy Service of the Sports Recovery Center, CEREDE, in Barcelona. All patients were football players (n=23), 23 men (100%) and no woman (0%). In the total study population (n=23) the clinical location corresponded to the osteotendinous junction of the lower pole of the patella, leading to the diagnosis of enthesopathy of the proximal patella. Based on the first observation and according to their score on the questionnaire, Victorian Institute of Sport Assessment-Patellar Tendon (VISA-P), we classified the patients into two groups: Group-1 (worse prognosis, n=12) who scored a VISA-P≤50 (52.2%) and Group-2 (better prognosis, n=11) with VISA-P score>50 (47.8%). All patients underwent EPI technique that was applied with an intensity of 3 mA during a period of 4 s, using the approved electro stimulator EPI (Epimedical scp, Barcelona 08017, Spain). The intervention was performed under ultrasound guidance with a portable ultrasound (General Electric LogicE).

Regarding the VISA-P score, Group 1 (n=12) in the first examination had a mean VISA-P score of 33.67 (SD±12.27, 95% CI 25.87 to 41.6) and in the last observation an average of 83.17 (SD±15.36, 95% CI 73.41 to 92.93), showing a statistically significant improvement in the results of the VISA-P questionnaire (p≤0.005). Group 2 (n=11) in the first observation had a mean VISA-P of 68.09 (SD±10.50, 95% CI 61.04 to 75.15) and in the last one, an average of 85.27 (SD±6.15, 95% CI 81.14 to 89.40) with statistically significant differences between the scores of the first and last observation (p≤0.005). In Group 1 (n=12), the average healing time was 4.66 weeks (95% CI 3.25 to 6.08) while in the group with the better prognosis (Group 2, n=11) it was 2.18 weeks (95% CI 2.57 to 4.39), both with statistically significant differences (p≤0.001). Regarding the estimation of the number of interventions with EPI needed to achieve healing, in the group with the worse prognosis (Group 1, n=12) the average number was 5.0 EPI sessions (95% 3.59 to 6.40) while in the group with better prognosis (Group 2 n=11), the mean number of sessions needed to achieve healing was 2.45 EPI sessions.

The ultrasound guided percutaneous electrolysis technique (EPI) has proved to be highly effective in the treatment of proximal patellar enthesopathy in a population of soccer players, with a significant improvement in 91.7% of the total sample (n=22), as measured by the Victorian Institute of Sport Assessment-Patellar Tendon (VISA-P) questionnaire. An analysis of Kaplan-Meier survival allowed us to estimate the time and number of sessions of EPI technique needed to achieve cure for both the group with worse prognosis (Group 1) and for the group with better prognosis (Group 2), independent of the stadium of the patient according to Blazina's Classification. EPI technology has proven to be very effective and therefore should not be a criterion for surgical intervention patients that, at first observation, are in stage III of Blazina's Classification. EPI technology has also proven to be effective in curing insertional patellar tendinopathy in soccer players regardless of duration and evolution of the clinical symptoms.

With ultrasound, we have measured the maximum length of the superficial and deep faces, bone to bone. These measurements were done in two positions: in maximal extension and 90° flexion. All samples were right knees, and there were 10 patients. Measurements were taken by the same technician (figure 1).

Figure 1.

Sagittal knee view.

Measurements were as follows: in maximal extension for the deep face, the mean value was 4.15cm (range 3.40–5.05) and for the superficial face, the mean value was 4.857cm (range 4.57–5.20). Alternatively, in 90° flexion, the deep face showed a mean value of 3.938 cm (range 2.77–4.64) while for the superficial face it was 4.916 (range 4.27–5.11). Variations in face lengths when we changed the knee position were 1.21% for the superficial face and 5.38% for deep face.

These results have demonstrated that the deep face had a greater percent increase in length than the superficial face when the knee changed position from extension to flexion. This study has some limitations- it was performed at only 90° flexion because the longitudinal probe is limited, and there are a low number of subjects. In conclusion, traction forces are probably more intense in the deep face than in the superficial face.

Muscle biopsies of nine partially torn and 15 fully torn supraspinatus tendons were compared histologically. H&E staining was performed to assess degenerative changes. Immunohistochemistry was used to assess slow and fast myosin heavy chains (type I and II fibres; Anti-slow skeletal myosin heavy chain antibody and Anti-fast skeletal myosin heavy chain antibody), satellite cells (CD56), proliferation (Ki67) and apoptotic cells (activated caspase-3; Asp175).

Full-thickness tears demonstrated significant atrophy of both slow (type I) and fast (type II) myosin heavy chains compared to partial tears. The area ratio of type II to type I was doubled in full-thickness tears. Partial thickness tears revealed significantly more satellite cells and proliferative activity than full-thickness tears. There was no detectable apoptosis using an antibody recognising active caspase-3.

Progression of rotator cuff tendinopathy is accompanied by a change in muscle fibre phenotype from endurance type I fibres to type II fibres more prone to fatigue, illustrating an aspect of muscle disuse. The rotator cuff muscle's ability to regenerate appears to be reduced when a full-thickness tear is established. Apoptosis does not appear to be of importance in muscle changes accompanying rotator cuff tendinopathy.

A retrospective analysis of all ultrasound scans of patellar tendons performed at Headley Court between 2008 and 2011 was performed. The scans were then graded by the lead author (JR) in conjunction with a consultant musculoskeletal radiologist (AW). For all abnormal tendons the following information was recorded; location, maximum tendon thickness, fibres involved, grey scale tendinopathy grade (0–3) after Archambault et al,1 neovascularity grade (modified Ohberg after Hoksrud et al2), presence of tendon calcification and bony irregularity.

One hundred and forty-three scans were identified. Of these 72 abnormal scans were suitable for the study. The age range was between 22 and 47 years with a mean average age of 30. There were 70 scans from male patients and 2 from female patients. The results are displayed in table 1 above.

Table 1

Patellar tendinopathy; distribution of site and severity of pathology

This study confirms that patellar tendinopathy is not restricted to the proximal pole. Although the proximal pole was the most commonly involved location, distal pole involvement was common occurring in 38% of scans. The vast majority of previous studies have concentrated on proximal disease to the neglect of distal disease. Involvement of the mid patellar tendon was less common and when it did occur it almost always occurred in conjunction with pathology of either the proximal and/or distal poles. Isolated involvement of the middle portion of the patellar tendon was very rare (occurring in only one scan). As a result of this study the following recommendations are made:

1. When scanning the patellar tendon all the anatomical areas are scanned carefully, including the distal pole.

2. The term ‘patellar tendinopathy’ is imprecise and insufficient. Abnormalities should be referred to as occurring at the specific site (ie, proximal and/or distal and/or mid tendon). The term ‘jumper's knee’ is equally imprecise and should be abandoned.

3. Future studies should stratify for the location of pathology in the patellar tendon as different treatments may have different results depending on the location of the pathology.

An observational, longitudinal and analytical study was designed with 66 cross-sectional ultrasonograms of PL (n=33 male players; mean age: 27.3 year (S.D.:4.72 year)). We obtained cross-sectional PL ultrasonograms, 5 mm from the distal border of the patella (LogiqE Ultrasound System, Enraf Nonius-General Electric). The records were taken bilaterally at the beginning and at the end of the season (6 months). The morphometric parameters were: echogenicity, echogenicity variation, width, thickness and circularity; and GLCM textural features: contrast and entropy. Image analysis was performed with ImageJ software v1.44. SPSS Statistics Software (V.19.0) was used for analysis of variance (ANOVA) for repeated measures. The size of effect was calculated with Cohen's d. All CIs were fixed at 95%.

The echogenicity (F=0.075; p=0.785; d=0.02) and echogenicity variation (F=3.308; p=0.074; d=0.17) showed no significant changes along the season. However the width was higher (F=6.144; p=0.016) at the end of season with a moderate effect size (d=0.36). The thickness (F=5.67; p=0.02) was lower with a small effect size (d=0.19) and the circularity (F=4.198; p=0.045) also was lower (d=0.17). As for the textural parameters, the contrast (F=19.438; p<0.001) increased at the end of the season with a moderate-high size effect (d=0.54); however, the entropy (F=0.081; p=0.78) did not change. See table 1 at the bottom of the previous page for descriptive statistics for statistically significant parameters.

Mechanical stress can generate adaptive changes in tendons. The study of these changes is complicated and invasive in living subjects, but with the advanced image analysis of ultrasonograms, it could be possible in an indirect way to detect these changes. Textural complex algorithms (as GLCM) provide information about the ultrasonography patterns. In this study the contrast that measures the relationship of grey level of pair of pixels was higher at the end of season; this could be related to a higher synthesis of collagen. In future studies, it would be interesting to find the relationship between biochemical markers and textural parameters.

Biopsies of about 5x5 mm were taken from the ventral part of the Achilles tendon and the paratendinous tissues of this area, from two groups. One group consisted of patients suffering from mid-portion tendinopathy with tendinosis (n=8). Normal controls (n=2) donated biopsies from the same area. Both procedures were guided by ultrasound and performed through a minimal skin incision. These biopsies were later sectioned and immunocytochemistry was used to study the expression patterns of PAR₄.

Double-staining with PAR₄ and substance P (SP) was performed.

The sections showed strong reactivity for PAR₄ in the blood vessels both in the tendon tissue proper as well as in the more abundant vascular areas ventral to the tendon in biopsies from both normal tendons and those from patients diagnosed with tendinosis. Tenocytes expressed PAR₄ to a varying degree (figure 1), with it being expressed more in cells with a rounded nuclei, primarily in tendons from the tendinosis group. PAR₄ was expressed on SP-positive nerve fibres in the paratendinous tissue (figure 2).

Figure 1.

(a) Tenocytes show reactions for PAR₄ (in red). Counterstained with DAPI. (b) Vessels positive for PAR₄.

Figure 2.

(a) A nerve fibre and vessel positive for PAR4. In b the nerve fibre shows reactivity for substance P.

These findings give basis for further studies into the interactions of SP-positive nerves and mast cells in tendon pathology. Earlier studies have shown regulation of vascular permeability and dilation, as well as fibroblast proliferation through activation of PARs. The PAR₄ may, through activation of proteases released from mast cells, to some extent be responsible not only for tenocyte proliferation and vascular regulation, but also for an enhanced pain signalling in tendinopathy through SP-positive afferents.

22 elite male Australian football players, some with history of tendinopathy (six and three players with a history of patellar and Achilles tendinopathy, respectively) were recruited. Players were scanned prior to the game and days 1, 2 and 4 post-game using UTC. A 1cm region at the midsubstance of the tendon was selected and the ultra-structure quantified into four echo-types based on the stability of the echopattern. Changes in the echopattern were compared over the 4 days using a related samples Friedmans two-way analysis of variance. If a significant difference in the median was observed, post-hoc (Wilcoxon signed rank test) analysis was performed to identify the differences between days 1, 2 and 4 and day 0.

Preliminary data analysis showed differences in baseline tendon structure in players with and without a history of lower limb tendinopathy. Further analysis will examine differences between groups in change over the 4 days, and examine intrinsic (age, mass) and extrinsic factors (game load, GPS data) that are associated with change in UTC parameters.

This study demonstrated the changes seen in the Achilles tendons of athletes after intense loading. The factors that affect the magnitude of the response were elucidated.

The purpose of this study was to prospectively investigate the clinical effect of treatment with AB or PRP injection in patients with chronic tendinopathy. Patients over 18 years old were eligible for the study if they had more than 3 months of symptoms and had failed typical conservative treatment such as physical therapy, corticosteroid injections, massage, acupuncture, and/or chiropractic. All tendons were evaluated with musculoskeletal ultrasound and patients received treatment with either AB, leukocyte-rich PRP (LR-PRP), or leukocyte-poor PRP (LP-PRP), injected under ultrasound guidance into the tendinopathic areas. Patients were followed using visual analogue pain scales (VAS), site specific validated outcome scores, and a Likert post-treatment scale at 6 weeks, 12 weeks, 6 months and a year. A decrease in VAS of 20 was considered a clinically significant improvement. Likert post-treatment ratings of much or completely resolved were also considered clinically significant.

99 tendons were treated with average age 48.5 years (range 19–82). 44% were female and 56% were male. Patients had symptoms for an average of 34.4 months prior to treatment. Conditions treated included lateral epicondylosis (17), proximal hamstring tendinosis (22), Achilles tendinosis (11), patellar tendinosis (10), plantar fasciosis (9) and other tendinopathies (30).

Of patients with at least 12 weeks follow-up, 10 had AB, 77 LR-PRP, and 12 LP-PRP injections. For AB injection the average duration of symptoms was 12.3 months and average follow-up was 22.2 weeks. 70% of ABI patients had some improvement, although only 40% improved at least 20 points on VAS. Average decrease in VAS was 15.2. Of those patients that improved, the average decrease in VAS was 23.1. 60% of those with AB injections considered themselves mostly or completely improved. For LR-PRP the average duration of symptoms was 35.8 months and average follow-up was 33.4 weeks. 78% of patients improved at all with 62% having at least a 20 point decrease in VAS. The average decrease in VAS was 21.8, but for those that improved, it was a 30.9 decrease. 54% of LR-PRP patients rated themselves as mostly or completely improved. For LP-PRP the average duration of symptoms was 37.6 weeks prior to treatment and average follow-up was 39.3 weeks. 92% of patients improved at all with 83% decreasing VAS by at least 20. The average decrease in VAS was 25 and for those who improved it was 29.1. 50% of LP-PRP patients rated themselves as mostly or completely improved.

Biologic therapies such as AB and PRP injection were moderately effective for treatment of recalcitrant tendinopathy, and PRP appears to be more effective than AB. Further studies comparing these treatments to each other, to other treatment options, and to placebo should be undertaken to better define their clinical utility and indications in the treatment of chronic tendinopathy.

107 patients (66 men, 41 women), mean age 43 years (range 24–77), with tendinosis in 125 Achilles tendons were, in local anaesthesia, treated with a US+CD-guided new surgical approach outside the ventral tendon. Pain during tendon loading activity (VAS) and satisfaction with treatment, were evaluated.

Before surgery, the mean VAS was 77. After surgery (follow up mean 18 months, range 6–33) the mean VAS was 2 in 111 tendons (89%) from satisfied patients back in full Achilles tendon loading activity.

US+CD-guided scraping/tenolysis in the region with rich vascularity and innervation outside the ventral tendon shows good short term clinical results in midportion Achilles tendinopathy.

This is a retrospective review of nine patients (mean age 47±10) treated with tendon reconstruction an average of 17 months following injury. Patients were evaluated and graded for bicep contour, range of motion, Mayo Elbow Performance Index (MEPI) and for bilateral elbow flexion and supination torque on a Biodex System 4 Pro dynamometer. Patient reported outcome questionnaires were also collected.

The mean Disabilities of the Arm, Shoulder, and Hand score (DASH), American Shoulder and Elbow Society score (ASES), and Mayo Elbow Performance Index (MEPI) were 11±10, 91±10, and 88±14 respectively. Eighty of nine subjects were somewhat or very satisfied with the reconstruction. Biceps contour was 4.7 cm above the antecubital fossa on the operative side versus 3.9 cm on the nonoperative side. No statistically different strength discrepancies were noted between the operative and nonoperative sides when comparing isometric supination strength (p=0.42) and flexion strength (p=0.17), as well as peak supination torque at 90 degrees of elbow flexion (p=0.09).

I agree with Tucker's and Collins’ claim about the current failure ‘to discover a candidate gene that can be conclusively linked...]]> 2013-05-10T00:31:18-07:00 info:doi/10.1136/bjsports-2012-091767 hwp:master-id:bjsports;bjsports-2012-091767 British Association of Sport and Excercise Medicine 2013-06-01 Editorial 47 9 533 535 Genetics [amp ] performance, SASMA Congress Wild Coast, South Africa 24[ndash ]27 October 2013 http://bjsm.bmj.com/cgi/content/short/47/9/536?rss=1 In September 2010, the first International Scientific Tendinopathy Symposium (ISTS) was held in Umeå, Sweden, to establish a forum for original scientific and clinical insights in this growing field of clinical research and practice. The second ISTS was organised by the same group and held in Vancouver, Canada, in September 2012. This symposium was preceded by a round-table meeting in which the participants engaged in focused discussions, resulting in the following overview of tendinopathy clinical and research issues. This paper is a narrative review and summary developed during and after the second ISTS. The document is designed to highlight some key issues raised at ISTS 2012, and to integrate them into a shared conceptual framework. It should be considered an update and a signposting document rather than a comprehensive review. The document is developed for use by physiotherapists, physicians, athletic trainers, massage therapists and other health professionals as well as team coaches and strength/conditioning managers involved in care of sportspeople or workers with tendinopathy.

In 2008, more than 12 million people worldwide were diagnosed with cancer (http://globocan.iarc.fr/). Because of improvements in early diagnosis and the introduction of more aggressive treatments over the past 20 years, cancer survivors are now living longer.1 However, treatment often leads to a range of undesirable and debilitating adverse effects.

In the linked meta-analysis, Fong and colleagues assess the effects of physical activity after treatment for cancer on 48 separate health related outcomes.2 The potential for exercise interventions to benefit survivors of cancer is a burgeoning area of research, and systematic reviews and meta-analyses have reported that exercise can reduce fatigue and improve functional outcomes and health related quality of life.3^–5 These reports have also...]]> 2013-05-10T00:31:18-07:00 info:doi/10.1136/bjsports-2012-d7998rep hwp:resource-id:bjsports;47/9/568 British Association of Sport and Excercise Medicine 2013-06-01 Exercise medicine highlights from the BMJ 47 9 568 568 Genetics [amp ] performance, SASMA Congress Wild Coast, South Africa 24[ndash ]27 October 2013 http://bjsm.bmj.com/cgi/content/short/47/9/569?rss=1 Background

Type XI collagen, which is expressed in developing tendons and is encoded by the COL11A1, COL11A2 and COL2A1 genes, shares structural and functional homology with type V collagen, which plays an important role in collagen fibril assembly. We investigated the association of these three polymorphisms with Achilles tendinopathy (AT) and whether these polymorphisms interact with COL5A1 to modulate the risk of AT.

184 participants diagnosed with chronic AT (TEN) and 338 appropriately matched asymptomatic controls (CON) were genotyped for the three polymorphisms.

Although there were no independent associations with AT, the TCT pseudohaplotype constructed from rs3753841 (T/C), rs1676486 (C/T) and rs1799907 (T/A) was significantly over-represented (p=0.006) in the TEN (25.9%) compared with the CON (17.1%) group. The TCT(AGGG) pseudohaplotypes constructed using these type XI collagen polymorphisms and the functional COL5A1 rs71746744 (-/AGGG) polymorphism were also significantly over-represented (p<0.001) in the TEN (25.2%) compared with the CON (9.1%) group.

The genes encoding structural and functionally related type XI (COL11A1 and COL11A2) and type V (COL5A1) collagens interact with one another to collectively modulate the risk for AT. Although there are no immediate clinical applications, the results of this study provide additional evidence that interindividual variations in collagen fibril assembly might be an important molecular mechanism in the aetiology of chronic AT.

A 12-week, medium-to-high intensity exercise intervention was completed by 183 volunteers (18–22 years). Data were sampled at baseline and after 12 weeks. Standard time domain, frequency domain and Poincaré HRV quantification techniques were implemented. Regression analysis was performed to determine the influences of the predictors (baseline values for low frequency  (LF), high frequency (HF), BMI, VO₂max, gender, blood pressure) on the exercise-induced response of the dependent variables (changes in HRV-indicator values).

Parameters found to be significant (p<0.05) predictors of exercise-induced changes were LF, HF and systolic blood pressure in, respectively, 10, 5 and 2 of the 12 regressions performed. The results indicated that the independent variables contribute between 12.83% and 29.82%, depending on the specific HRV indicator, to the exercise-induced changes in the autonomic nervous system.

Preintervention autonomic status, as represented specifically by LF, is the most important determinant of cardiac autonomic response to an exercise intervention in a healthy study population. Baseline autonomic function could thus be a significant confounder in the outcome of exercise study results.

210 male Gabonian football players were examined with history, physical examination, ECG and echocardiography.

On history, 19 players (9%) referred atypical chest discomfort/oppression. Familial sudden death was referred by 36 (17%). No anomalies were detected at physical examination. ECG showed large proportions of ‘training-related’ abnormalities, that is, ST-segment elevation in precordial leads in 150 (71.4%), and isolated increase in R/S-wave voltage in 116 (55.2%). A substantial subset (12.4%) showed ‘training-unrelated’ abnormalities, that is, inverted T-waves in 10 (4.8%), left atrial enlargement in 8 (4%), deep Q-waves in 3 (1.4%). On echocardiography, one athlete meet criteria for hypertrophic cardiomyopathy (HCM); none showed evidence for arrhythmogenic right ventricular cardiomyopathy (ARVC) or dilated cardiomyopathy (DCM). Other abnormalities included mitral valve prolapse in three, atrial septal defect in two and pulmonary hypertension in one.

About 12% of native African athletes showed ECG abnormalities unrelated to training and requiring additional testing and periodical follow-up. Structural abnormalities were found, however, in a minority (5%), including HCM in one, but no ARVC or DCM. In conclusion, this study demonstrates that preparticipation CV screening is efficient to identify (or raise suspicion) for CV abnormalities in native African athletes, but challenging for conclusive identification of cardiac diseases in the difficult scenario of a developing African country.

Between 1996 and 2011, 245 male and 84 female adolescent BA from a wide variety of sporting disciplines underwent cardiac evaluation including ECG and echocardiography. Athletes exhibiting T-wave inversions and/or echocardiographic LVH were investigated further for quiescent cardiomyopathies. Results were compared with 903 adolescent white athletes (WA) and 134 adolescent sedentary black controls (BC).

LVH on echocardiography was present in 7% of BA compared to only 0.6% of WA and none of the BC. In the very young (<16 years), 5.5% of BA, but none of the WA, demonstrated LVH. Within the BA group, LVH was more prevalent in men compared to women (9% vs 1.2%, p=0.012). T-wave inversions were present in 22.8% BA, 4.5% WA and 13.4% BC. T-wave inversions in BA occurred with similar frequency in men and women and were predominantly confined to leads V1–V4. T-wave inversions in the lateral leads, commonly associated with cardiomyopathies, were present in 2.4% of BA. On a further evaluation and mean follow-up of 8.3 years, none of the athletes exhibited HCM.

Athletic training has a pronounced effect on adolescent BA. Black athletes as young as 14 years of age may exhibit left ventricular wall thicknesses of 15 mm and marked repolarisation changes resembling HCM. Male and female BA demonstrate a high prevalence of T-wave inversions.