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Background: The aim of this study was to gain a deeper understanding of the gender differences in knee osteoarthritis (OA) by evaluating the differences in gait spatio-temporal parameters and the differences in pain, quality of life and function between males and females suffering from knee OA., Methods: 49 males and 85 females suffering from bilateral medial compartment knee OA participated in this study. Each patient underwent a computerized gait test and completed the WOMAC questionnaire and the SF-36 health survey. Independent t-tests were performed to examine the differences between males and females in age, BMI, spatio-temporal parameters, the WOMAC questionnaire and the SF-36 health survey., Results: Males and females had different gait patterns. Although males and females walked at the same walking speed, cadence and step length, they presented significant differences in the gait cycle phases. Males walked with a smaller stance and double limb support, and with a larger swing and single limb support compared to females. In addition, males walked with a greater toe out angle compared to females. While significant differences were not found in the WOMAC subscales, females consistently reported higher levels of pain and disability., Conclusion: The spatio-temporal differences between genders may suggest underlying differences in the gait strategies adopted by males and females in order to reduce pain and cope with the loads acting on their affected joints, two key aspects of knee OA. These gender effects should therefore be taken into consideration when evaluating patients with knee OA., Trial Registration: The study is registered in the NIH clinical trial registration, protocol No. NCT00599729.

In order to determine the mechanisms by which a chronic inflammatory network can be maintained in the arthritic joint, we examined whether fibroblast-like synoviocytes (FLS) could provide feedback signals after their stimulation by inflammatory cytokines. FLS and dermal fibroblasts (DF) were derived from rheumatoid arthritis (RA), osteoarthritis (OA) and post-trauma patients. These two cell types were then stimulated with 10 nanogram/ml of TNFalpha, IL-1beta and IL-17 alone or in combination treatments. Specific mRNA expression of IL-23 p19 was quantitated by real-time PCR and its protein by immunoprecipitation. A striking specific synergistic induction of IL-23 p19 versus IL-12 p35 mRNA expression was noted after stimulation with IL-17 and TNFalpha in FLS, and to a lesser degree in DF (p<0.043). This synergistic response was composed of an initial priming step by IL-17, thus making FLS hyperresponsive to TNFalpha-mediated stimulation. In contrast, IL-1beta mediated induction of IL-23 p19 expression was cell-specific. Induction of IL-23 p19 expression by IL-1beta was present in FLS but almost absent in the DF derived from the same patients. Furthermore, IL-1beta did not synergize with IL-17 to induce IL-23 p19 expression. Immunoprecipitation of FLS cellular lysates after stimulation with IL-17 and TNFalpha detected p19 protein and this was enhanced by the addition of IL-1beta. However, no co-immunoprecipitation of the p40 subunit of IL-23 was noted from the same cells. Thus, FLS are potently regulated by inflammatory cytokines to specifically express IL-23 p19. Additional byproducts of the inflammatory milieu may be required for the generation and secretion of bioactive IL-23.

Synovial plicae are membranous inward folds of the synovial lining of the knee joint capsula. Such folds are regularly found in the human knee, but most are asymptomatic and of little clinical consequence. However, they can become symptomatic and cause knee pain. In this review, we will discuss medial plica syndrome. Medial plica irritation of the knee is a common source of anterior knee pain. The main complaint is an intermittent, dull, aching pain in the area medial to the patella above the joint line and in the supramedial patellar area. Pain increases with activity, especially when knee flexion and extension are required. Treatment includes physiotherapy, reducing activity, and rest. In cases that do not respond initially to an exercise program, corticosteroid injections and non-steroidal antiinflammatory medication are given. Results of conservative treatment seem to be more appropriate in young patients with a short duration of symptoms. If conservative treatment fails, surgical treatment using arthroscopy is appropriate. During arthroscopy, excision of the whole plica should be achieved.

Random amplified polymorphic DNA analysis was carried out in 35 autochthonous table grapevine cultivars grown in Coruh valley. Fifty-five oligonucleotide primers were screened on cultivars, and among them, 12 primers showed clear polymorphic patterns. PCR amplification with 12 primers generated a total of 157 polymorphic bands. There was genetic variation among the cultivars with values of genetic diversity ranging from 0.19 to 0.72 using the Jaccard coefficient. UPGMA analysis of the distance matrix resulted in a dendrogram with two main clusters. The first cluster included 28 cultivars and the second 7 cultivars. The greatest genetic similarity was observed between cultivars Gah and Kolik, while the greatest dissimilarity was observed between cultivars Gah and Siyah Kus Uzumu. The dendrogram revealed that the cultivars present in Coruh valley can be distinguished to a relatively high degree.

Osteochondritis dissecans of the knee is diagnosed at an increasing rate among adolescents and young adults. One of the reasons is due to the increasing number of sports participants among these populations. Although many theories exist, the cause of osteochondritis dissecans is unknown. Early diagnosis is very important. While adult type osteochondritis dissecans is unstable, in most young patients it is stable, and patients with an intact articular surface have a good chance to heal with non-operative treatment and cessation of physical activity. The value of complementary treatment (bed rest, partial weight bearing, bracing aimed at reducing weight bearing of the involved knee) is unknown. Patients with open physes and stable lesions, who failed non-operative treatment, may be treated with local bone drilling, encouraging lesion healing. As the disease progresses, more aggressive measures should to be taken, whilst decreasing success ratios are expected. The healing potential of the lesion may be evaluated by magnetic resonance imaging. Most adult type osteochondritis dissecans patients, as most young patients, with unstable lesions and loose bodies within their knees, are treated with fixation of the lesions and even bone grafting. Many unstable lesions will heal after fixation, but the long-term prognosis is elusive. Chronic loose bodies are very difficult to fix, with less favorable outcomes. Excision of large lesions originating from weight bearing cartilage is not favorable and different rehabilitation measures of local cartilage damage are not encouraging.

The response of fibroblast-like synoviocytes (FLS) to inflammatory stimuli was compared to their, respectively, derived dermal fibroblasts (DF) to determine whether regulatory controls exist within FLS to insure normal joint homeostasis. We further analyzed whether the loss of the normal regulatory controls present within the FLS could predispose to the development of non-rheumatic joint disease (non-RA). Primary fibroblast cell lines were generated from synovial and skin tissue from ten rheumatoid arthritis (RA) and ten non-RA patients. Cell lines were pulse labeled with [(35)S]-methionine and stimulated with TNFalpha or IL-1beta. Protein synthesis of IL-1beta, IL-6 and IL-8 was quantitated following immunoprecipitation. Gene expression was determined by Northern blot analysis. We noted, IL-1beta was minimally detected in FLS under nonstimulated conditions. In response to stimulation with IL-1beta or TNFalpha, production of IL-1beta was found to be 3.5 and 5-fold lower in FLS, respectively, when compared to DF from the same individual. In contrast, the production of IL-6 and IL-8 in FLS upon stimulation was 3-fold and 1.6-fold higher, respectively, than in DF. Furthermore, induced IL-1beta production in FLS, normalized relative to their, respectively, stimulated DF, was 2.5 times higher in non-RA versus RA-derived cells (p=0.032), an effect noted even after several passages of growth. Our data suggest that inductive expression of IL-1beta in FLS is under specific inhibitory control. Increased production of IL-1beta in FLS of susceptible individuals may lead to a higher risk of developing severe joint damage even in the absence of systemic inflammation.

Study Design: A retrospective evaluation of anterior instrumentation of the vertebral bodies in the thoracolumbar spine., Objective: To evaluate the possibility of preserving the segmental vessels following anterior instrumentation., Summary of Background Data: Occlusion of the segmental vessels, routinely performed during anterior spine instrumentation, might cause neurologic injury secondary to cord ischemia., Methods: The medical data of 29 patients following anterior instrumentation of the vertebral bodies at the thoracolumbar spine were reviewed. All underwent surgery recently when we decided to preserve the segmental vessels whenever possible. We sought the reasons that enabled us to do so regarding age, gender, underlying pathology, surgical technique, operation duration, instrumentation type and size, and location in the vertebral body., Results: In only 7 patients, fused between T10 and L5, were we able to preserve the segmental vessels. All were instrumented with one 6.25-7-mm wide screw in each vertebral body connected by one rod, approximately half the screws above and half below the segmental vessels. In 22 patients, we were unable to preserve the vessels due to the need to insert 2 screws or a large threaded wide vertebral cage into each vertebra., Conclusions: There is adequate space anteriorly in the vertebral body, above and below the segmental vessels, for the insertion of one screw, even with staples.

The aim of this study is to investigate in vitro antimicrobial and antioxidant activities of the methanol extracts of Parmelia saxatilis (L) Ach., Platismatia glauca (L.) W.L. Club. & C.F. Culb., Ramalina pollinaria (Wesstr.) Ach., Ramalina polymorpha (Liljeblad) Ach. and Umbilicaria nylanderiana (Zahlbr.) H. Magn. Antioxidant activity was evaluated by two separate methods: scavenging of free radical DPPH and the inhibition of linoleic acid oxidation. Extracts of Parmelia saxatilis, Platismatia glauca., Ramalina pollinaria and Ramalina polymorpha did not exert any activity in both assays, whereas those of Umbilicaria nylanderiana provided 50% inhibition at 400.2 microg/ml concentration in the former and gave 53% inhibition at 2g/l concentration. Total phenolic constituents of extracts from lichen species tested (P. saxatilis, P. glauca, R. pollinaria, R. polymorpha and U. nylanderiana) were 1.0% (w/w), 1.1% (w/w), 1.0% (w/w), 0.8% (w/w) and (3.0% w/w), respectively (as gallic acid equivalent); implying that the observed activity could be related to the amount of polar phenolics. Extracts were also found to possess antimicrobial activity against some test bacteria and fungi and yeast.

Bipartite patella, although usually asymptomatic, can become a source of persistent pain following injury. When nonoperative treatments such as physiotherapy and rest fail to produce any resolution in the symptoms, surgery is usually performed. This may include excision of the painful fragment, lateral retinacular release, or detachment of the vastus lateralis insertion, generally performed as open surgical procedures. In the case of vastus lateralis release, however, there has been recent report of statistically better results using an arthroscopic technique. Furthermore, open partial patellectomy has been criticized as being invasive and at times requiring long postoperative rehabilitation. We describe the case of a 26-year-old man who presented with a painful bipartite patella fragment that had not responded symptomatically to nonsurgical treatment. The painful fragment was removed arthroscopically as a day case under a general anesthetic. This was carried out through 3 portals and involved the use of a combination of probe, periosteal elevator, and arthroscopic shaver. Using this technique, we were able to minimize the surgical trauma associated with an open surgical procedure. The early result of this case encourages the use of an arthroscopic technique for partial patellectomy in the surgical treatment of a bipartite patella.

Shoulder pain and immobility comprise a multifactorial disorder apparently affected by pain inhibiting joint motion. As the syndrome is very common, many patients do not undergo detailed imaging studies before treatment. This study compared a series of 7 patients in whom a neoplasm was the underlying cause for the stiff shoulder with a series of 50 patients with primary or secondary frozen shoulder. In addition to a detailed history being taken, the Disabilities of the Arm, Shoulder, and Hand (DASH) upper limb outcomes data collection questionnaire was completed and physical examination, radiography, ultrasonography, and bone scanning were performed in all cases. In the cases of tumor, the presenting symptom was a stiff shoulder without radiographic abnormality in 7 of 67 patients with shoulder girdle neoplasms who were seen at our musculoskeletal oncology clinic. The tumors included osteoid osteoma, osteoblastoma, metastatic carcinoma, chondrosarcoma, periosteal lipoma, and acute lymphoblastic lymphoma. The diagnosis was established in all cases by an area of focal isotope uptake demonstrated by a routine technetium 99 methylene diphosphonate bone scan. In a single case of metastatic colon carcinoma, the diagnosis could only be established by magnetic resonance imaging, as the radiographs were normal and the bone scan demonstrated diffuse uptake over the proximal humerus. The patients whose frozen shoulder was caused by an underlying tumor were significantly younger and had a lower fatigue/energy dimension score on the RAND Short Form-36 health survey. The most useful diagnostic test appears to be a discrete area of bony tenderness, present in 7 of 7 patients with tumor and in only 5 of 50 patients in the control group. Although an underlying tumor is a rare cause of frozen shoulder syndrome, the potential grave consequences of misdiagnosis and the possibility of performing an unnecessary and ineffective invasive procedure should prompt physicians to increased vigilance. In patients with discrete bony tenderness elicited by light tapping, a bone scan should be ordered and magnetic resonance imaging should be considered.

Objective: Hyaluronic acid (HA) polymers have been found to be useful as viscosupplements for the treatment of osteoarthritis (OA) in a number of clinical studies. It appears that HA with high molecular weights (HMW) are more effective than low molecular weight HA polymers., Methods: A single blind, initial randomized study was conducted involving two randomly selected patient groups, which received injections of either placebo or BioHy, a highly purified HMW HA produced by bacterial fermentation. HA was administered intra-articularly and several functional tests, including pain level, stiffness, and physical function, were used to score efficacy at various intervals throughout the study., Results and Conclusion: The results through week 20 indicate that BioHy provides relief for osteoarthritic patients without causing adverse effects, although the study was not sufficiently powered to obtain statistically significant differences between the treatment groups.

Background: Articular cartilage is incapable of undergoing self-repair since chondrocytes lose their mitotic ability as early as the first year of life. Defects in articular cartilage, especially in weight-bearing joints, will predictably deteriorate toward osteoarthritis. No method has been found to prevent this deterioration. Drilling of the subchondral bone can lead to fibrocartilage formation and temporary repair that slowly degrades. Animal experiments indicate that introducing proliferating chondrocytes such as cultured articular chondrocytes can reliably reconstruct joint defects., Objectives: To describe our clinical experience in culturing and transplanting autologous chondrocytes., Methods: Biopsies were obtained from 10 patients, aged 18-45, undergoing a routine arthroscopy in which a cartilage defect was identified with indications for cartilage transplantation. The biopsies were further processed to establish chondrocyte cultures. ACT was performed in 8 of the 10 patients because of persistent symptoms for at least 2 months post-arthroscopy. All patients (6 men and 2 women) had a grade IV cartilage defect in the medial or lateral femoral condyle, and three had a defect in the trochlear region as well. Biopsies were removed from the lateral rim of the superior aspect of the femur, and cells were cultured in a clean room. Following a 2 order of magnitude expansion, cells were implanted under a periosteal flap., Results: The eight patients implanted with autologous cells were followed for 6 months to 5 years (average 1 year). Complaints of giving-way, effusion and joint locking resolved in all patients, and pain as assessed by the visual analogue score was reduced by an average of 50%. Follow-up magnetic resonance imaging studies in all patients revealed that the defects were filled with tissue having similar signal characteristics to cartilage., Conclusions: Chondrocyte implantation is a procedure capable of restoring normal articular cartilage in cases with isolated joint defects. Pain can be predictably reduced, while joint locking and effusion are eliminated. The effect on osteoarthritis progression in humans has not yet been elucidated.

Osteoarthritis results from progressive catabolic loss of cartilage proteoglycans due to imbalance between synthesis and degradation. The availability of glucosamine, an intermediate in mucopolysaccharide synthesis, can be rate-limiting for proteoglycan production in cartilage tissue culture. 57 patients suffering from osteoarthritis of the knee were randomized into a group treated for 4 weeks with daily i.v. glucosamine sulfate (GS) together with 800 mg chondroitin sulfate, and a placebo group. Knee pain at rest, on movement and on palpation, as well as range of knee motion were then recorded. In the GS group, there was significant reduction of clinical symptoms (p < 0.01), but no significant reduction in the placebo group. Physicians' assessment of tenderness and range of motion were significantly in favor of the GS group (p < 0.01). In those treated with glycosamine there were no adverse reactions and no changes in laboratory blood tests. We conclude that GS can be considered the drug of choice for prolonged treatment of osteoarthritis.

Adult articular cartilage lacks the capacity for self-repair. The limiting factor appears to be the inability of chondrocytes to proliferate while embedded in the extracellular matrix typical of hyaline cartilage. Cartilage defects larger than 1 cm2 change articular biomechanics and lead to eventual osteoarthritis and joint destruction. During the past decade, several competing techniques have evolved to stimulate articular cartilage repair. Small lesions can be successfully treated by either micro-fracture or osteochondral cylinder grafting. The latter technique allows immediate weight bearing but leads to damage of previously uninvolved areas of articular cartilage, which limits its application to lesions of less than 2 cm2. When the damaged area is more extensive, grafting of autologous chondrocytes should be considered. First a diagnostic arthroscopy is performed to assess the damaged area and a small cartilage biopsy is taken. 6 weeks later, arthrotomy and chondrocyte transplantation are performed. In the interval, the antologous chondrocytes have expanded by 2 to 3 orders of magnitude. Our experience to date includes 10 cases with follow-up of 6 months to 5 years. Preoperative complaints of crepitation and locking disappear. There is functional improvement and pain reduction of approximately 50%. This procedure, currently limited to patients under 55 years of age with limited damage to an articular surface, for the first time allows reconstruction of damaged articular areas without resorting to allografts.