Cytokines and apoptosis in supraspinatus tendinopathy.

The role of inflammatory cells and their products in tendinopathy is not completely understood. Pro-inflammatory cytokines are upregulated after oxidative and other forms of stress. Based on observations that increased cytokine expression has been demonstrated in cyclically-loaded tendon cells we hypothesised that because of their role in oxidative stress and apoptosis, pro-inflammatory cytokines may be present in rodent and human models of tendinopathy. A rat supraspinatus tendinopathy model produced by running overuse was investigated at the genetic level by custom micro-arrays. Additionally, samples of torn supraspinatus tendon and matched intact subscapularis tendon were collected from patients undergoing arthroscopic shoulder surgery for rotator-cuff tears and control samples of subscapularis tendon from ten patients with normal rotator cuffs undergoing arthroscopic stabilisation of the shoulder were also obtained. These were all evaluated using semiquantitative reverse transcription polymerase chain-reaction and immunohistochemistry. We identified significant upregulation of pro-inflammatory cytokines and apoptotic genes in the rodent model (p = 0.005). We further confirmed significantly increased levels of cytokine and apoptotic genes in human supraspinatus and subscapularis tendon harvested from patients with rotator cuff tears (p = 0.0008). These findings suggest that pro-inflammatory cytokines may play a role in tendinopathy and may provide a target for preventing tendinopathies.

Telangiectatic dedifferentiation of a parosteal osteosarcoma.

A unique case of parosteal osteosarcoma (POS) of the proximal femur, with areas of telangiectatic dedifferentiation, in a 28-year-old woman is reported. The patient had a 7-week history of pain and swelling in her right thigh. A biopsy diagnosis of POS was established. The patient was treated with two cycles of intraarterial chemotherapy, followed by limb salvage surgery. Histological examination of the resected specimen showed POS with areas of dedifferentiation composed of highgrade telangiectatic osteosarcoma with associated secondary aneurysmal bone cyst change.

The protective effects of meniscal transplantation on cartilage. An experimental study in sheep.

BACKGROUND: Meniscal loss may result in arthritis. The aim of this study was to establish a simple operative method for meniscal transplantation in a large-animal model and to determine whether meniscal transplantation provides protection of the articular surfaces, whether meniscal allografts have the same protective effect as meniscal autogenous grafts, and whether there is any rejection phenomenon associated with meniscal allografts. METHODS: Twenty-eight sheep were divided into four study groups, which were treated with (1) a sham operation (four sheep), (2) a meniscectomy (eight sheep), (3) a meniscal autogenous graft (eight sheep), or (4) a meniscal allograft (eight sheep). The meniscal transplant was secured with three suture anchors to the tibia. At four months after the operation, macroscopic and microscopic evaluations of the articular cartilage and the menisci of the sheep knees were performed in a blinded fashion. RESULTS: The group treated with the sham operation had no cartilage damage and had normal meniscal tissue. The meniscectomies resulted in significant macroscopic and microscopic damage to the articular cartilage in the medial compartment. The mean score (and standard error of the mean) for macroscopic damage to the cartilage in the group treated with the meniscectomy was 6.5+/-0.8 points compared with 3.9+/-0.7 points in the group treated with the autogenous graft and 4.3+/-0.6 points in the group treated with the allograft (p<0.05). The size of the area of damaged articular cartilage was reduced by approximately 50 percent in both groups treated with a meniscal transplant compared with the group treated with the meniscectomy (p<0.05). There were no significant differences between the group treated with the autogenous graft and that treated with the allograft. The histological appearance of the meniscal autogenous grafts was within normal limits. Interestingly, all of the allografts had evidence of fibrinoid degeneration with areas of hypocellularity and cloning of chondroid cells. CONCLUSIONS: These results suggest that meniscal transplantation provides noticeable although not complete protection against damage to the articular cartilage after a meniscectomy. The meniscal allografts were just as effective in providing this protection as were the meniscal autogenous grafts.

Overuse tendinosis, not tendinitis part 1: a new paradigm for a difficult clinical problem.

Overuse tendinopathies are common in primary care. Numerous investigators worldwide have shown that the pathology underlying these conditions is tendinosis or collagen degeneration. This applies equally in the Achilles, patellar, medial and lateral elbow, and rotator cuff tendons. If physicians acknowledge that overuse tendinopathies are due to tendinosis, as distinct from tendinitis, they must modify patient management in at least eight areas. These include adaptation of advice given when counseling, interaction with the physical therapist and athletic trainer, interpretation of imaging, choice of conservative management, and consideration of whether surgery is an option.

Histopathology of common tendinopathies. Update and implications for clinical management.

Tendon disorders are a major problem for participants in competitive and recreational sports. To try to determine whether the histopathology underlying these conditions explains why they often prove recalcitrant to treatment, we reviewed studies of the histopathology of sports-related, symptomatic Achilles, patellar, extensor carpi radialis brevis and rotator cuff tendons. The literature indicates that healthy tendons appear glistening white to the naked eye and microscopy reveals a hierarchical arrangement of tightly packed, parallel bundles of collagen fibres that have a characteristic reflectivity under polarised light. Stainable ground substance (extracellular matrix) is absent and vasculature is inconspicuous. Tenocytes are generally inconspicuous and fibroblasts and myofibroblasts absent. In stark contrast, symptomatic tendons in athletes appear grey and amorphous to the naked eye and microscopy reveals discontinuous and disorganised collagen fibres that lack reflectivity under polarised light. This is associated with an increase in the amount of mucoid ground substance, which is confirmed with Alcian blue stain. At sites of maximal mucoid change, tenocytes, when present, are plump and chondroid in appearance (exaggerated fibrocartilaginous metaplasia). These changes are accompanied by the increasingly conspicuous presence of cells within the tendon tissue, most of which have a fibroblastic or myofibroblastic appearance (smooth muscle actin is demonstrated using an avidin biotin technique). Maximal cellular proliferation is accompanied by prominent capillary proliferation and a tendency for discontinuity of collagen fibres in this area. Often, there is an abrupt discontinuity of both vascular and myofibroblastic proliferation immediately adjacent to the area of greatest abnormality. The most significant feature is the absence of inflammatory cells. These observations confirm that the histopathological findings in athletes with overuse tendinopathies are consistent with those in tendinosis--a degenerative condition of unknown aetiology. This may have implications for the prognosis and timing of a return to sport after experiencing tendon symptoms. As the common overuse tendon conditions are rarely, if ever, caused by 'tendinitis', we suggest the term 'tendinopathy' be used to describe the common overuse tendon conditions. We conclude that effective treatment of athletes with tendinopathies must target the most common underlying histopathology, tendinosis, a noninflammatory condition.

Morton's metatarsalgia: sonographic findings and correlated histopathology.

The results of 79 high resolution ultrasound examinations of the forefoot that were performed for suspected Morton's metatarsalgia were retrospectively assessed. Scans were only obtained if the pain was poorly localized or if there were atypical features that made the clinical diagnosis uncertain. Ultrasound detected 92 hypoechoic intermetatarsal web space masses in 63 patients. Surgery was performed on 23 web spaces in 22 patients where the response to nonsurgical management had been poor. The surgical specimens were retrieved and reviewed by a pathologist in 21 cases. The histopathology in 20 of 21 operated cases was that of Morton's neuroma; however, prominent mucoid degeneration was also found to involve the adjacent loose fibroadipose tissues in 19 of 20 neuroma specimens. Ultrasound was sensitive in the detection of web space abnormality (sensitivity, 0.95), but could not clearly separate Morton's neuroma from associated mass-like mucoid degeneration in the adjacent loose connective tissues. The implications of these observations for both diagnosis and treatment are discussed.

Expression of growth factors in the mandibular distraction zone: a sheep study.

Interest in craniofacial osteodistraction has increased in recent years parallel with the growing attention given to the role of growth factors in tissue healing and regeneration. This study was embarked upon to investigate the expression of bFGF, TGF-beta and IGF-1 in the distraction zone of the mandible. Fourteen growing sheep were allocated to three experimental groups. Six animals were allocated to Groups A and B (n = 12) and underwent bilateral mandibular corticotomies with fixation of an external lengthening device. The distraction protocol consisted of a rate of 1.0 mm/day (twice daily) for 20 days followed by a consolidation phase of 20 days after which the sheep were sacrificed. Group C comprised of age matched sham operated animals (n = 2). Bone histochemistry for growth factors were performed in the harvested mandibles. A strong staining of bFGF was seen in the osteoblasts, osteocytes and osteoid matrix following 20 days of distraction and 20 days of consolidation compared to the control group. TGF-beta and IGF-1 demonstrated mild but clear staining in osteocyte and osteoblast cells and TGF-beta stained positively in the osteoid seam in the experimental groups. These finding suggest that bFGF, IGF-1 and TGF-beta may play different roles in the remodelling phase of distraction osteogenesis.

The role of latency in mandibular osteodistraction.

Even though osteodistraction has been well established in the extremities, the parameters used in craniofacial distraction have been essentially borrowed from orthopaedic experience. Latency is widely practised but its relevance has not been fully investigated. The purpose of this study was to establish the role of latency in mandibular distraction osteogenesis. Twenty-two growing Wethers sheep were allocated to four experimental groups. Six animals were allocated to each of Groups A, B and C and underwent bilateral mandibular corticotomies and attachment of an external lengthening device. Latent periods of 0, 4 and 7 days respectively were observed prior to beginning distraction. The distraction protocol consisted of a rate of 0.5 mm twice daily for 20 days, followed by a consolidation phase of 20 days after which the sheep were killed. Histology, bone densitometry and 3-point mechanical testing were performed on the harvested mandibles. Group D formed the control group (n = 4). Histologically, the distracted bone exhibited bone formation primarily via intramembranous ossification with scattered islands of cartilage. The regenerated bone had mechanical properties significantly weaker than the undistracted control group (P < 0.05), but between the experimental groups no statistically significant differences were demonstrable either in mechanical strength or DEXA density. These data indicate that a change in latency does not alter the properties of the regenerated bone in mandibular distraction osteogenesis and indeed no latent interval may be necessary at all in craniofacial distraction. This has implications for the duration of device fixation in distraction procedures.

Cytokines and matrix metalloproteinases mRNA expression in archival human tissues from failed total hip arthroplasty using in situ hybridization and color video image analysis.

Reports on the histological and biochemical nature of periprosthetic fibrous/granulomatous tissue has, to date, been largely limited to frozen tissue sections. This study reports the cytokine and matrix metalloproteinase profiles found in periprosthetic interface tissues in THA which have failed due to aseptic loosening and in capsular tissues obtained at primary surgery. The study employs immunohistochemistry, in situ hybridization, and color video image analysis on formalin fixed and paraffin embedded sections.

Patellar tendinosis (jumper's knee): findings at histopathologic examination, US, and MR imaging. Victorian Institute of Sport Tendon Study Group.

PURPOSE: To determine the histopathologic findings of patellar tendinosis ("jumper's knee") demonstrated with ultrasonography (US) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twenty-four athletes (28 knees) with jumper's knee (23 men, one women; mean age, 30.9 years) scheduled to undergo open tenotomy underwent US patellar tendon examination. Seventeen patients (19 knees) also underwent MR imaging. Tissue was obtained for histopathologic examination in all 28 cases. Eleven age-, height-, and weight-matched athletes (22 knees) without previous knee symptoms served as control subjects for the US examination. Control material for histopathologic examination was obtained in 20 cadavers (39 knees). Data were analyzed with standard statistical methods. RESULTS: MR imaging and US both revealed an abnormal zone at the proximal patellar tendon attachment. Histopathologic examination revealed mucoid degeneration in all tendons in patients and in 8% (three of 39) of tendons in cadavers (P < .01). CONCLUSION: Jumper's knee is characterized by consistent changes at MR imaging, US, and histopathologic examination and is appropriately described as patellar tendinosis.

Myxoid chondrosarcoma of soft tissue and bone: a retrospective study of 11 cases.

This article describes 11 cases of myxoid chondrosarcoma (MCS), with 10 arising in soft tissues and one developing in bone. Most of the tumors (six) were located in the lower extremities. Two lesions developed in the fingers, a previously unreported location for MCS. Four cases showed secondary bone destruction, which is a rare feature of this tumor. S100 protein was expressed by tumor cells in all the specimens. Four out of eight tumors studied by electron microscopy contained intracisternal microtubular structures. Two tumors showed areas of spindle cell proliferation that merged with the areas of typical myxoid pattern. The cells in these areas had fibroblastic/myofibroblastic features by electron microscopy and were found to express cytokeratin by immunohistochemistry. The concomitant expression of cytokeratin and S100 protein in the spindle cells suggests that they represent a less differentiated cartilaginous component with unusual features. The clinical significance of the presence of such spindle cell areas presently remains unknown. Although myxoid chondrosarcoma is a slow-growing tumor, it has a high potential for metastases. Four of 11 patients in this series developed metastases.

Tumoral calcium pyrophosphate deposition disease.

A report of two patients in which a soft tissue mass, initially regarded as a malignant tumor, was shown to be the result of calcium pyrophosphate deposition disease. The first case, a woman aged 71 years, presented with a mass involving the right fifth finger. In the second case, also a woman aged 71 years, the lesion involved the tissues adjacent to the right hip. Each lesion consisted of a mass of highly cellular tissue containing deposits of calcium pyrophosphate dihydrate crystals. The clinical, radiological, and pathological features of the two cases are compared with those of seven similar cases reported in the literature.

Small bowel capillary dilatation in portal hypertension.

A patient with small bowel capillary dilatation and cirrhosis is reported. This patient had persistent, unexplained gastrointestinal bleeding. Small bowel capillary dilatation appears to be unique to patients with portal hypertension. The possible role of small bowel capillary dilatation in causing gastrointestinal bleeding is discussed.

Intermittent claudication. The effect of physical training on walking tolerance and venous lactate concentration.

Twenty-one patients with intermittent claudication underwent a physical exercise program lasting 8 weeks. The patients were classified on the basis of maximal walking tolerance (MWT) and diagnosis at the initial examination. Seven of the patients had a MWT less than 1,000 m and no symptoms of chronic obstructive airways disease (COAD) or angina (group A), seven had a MWT less than 1,000 m plus angina and/or COAD (group B) and seven had an unlimited (greater than 1,250 m) MWT (group C). At the completion of the training program all three groups showed a significant improvement in walking distance to pain and stress test capacity. During the post-training walking tolerance test, the venous lactate concentrations in group A were lower after 2 min and 4 min of exercise, and at exhaustion (P less than 0.05). Group A patients showed a significant correlation between an increase in MWT after training and a decrease in maximum lactate concentration measured during walking. Although the patients in group B had a significant increase in MWT, blood lactate concentrations in this group were not always decreased by physical training. Group C lactate concentrations were lower after 8 min, 15 min, and 30 min of walking (P less than 0.05). It is concluded that a physical training program increases walking tolerance in different categories of claudicants, and possible mechanisms for the improvement are discussed.