Heparanase is expressed in adult human osteoarthritic cartilage and drives catabolic responses in primary chondrocytes.

OBJECTIVES: The chondrocytes' pericellular matrix acts as a mechanosensor by sequestering growth factors that are bound to heparan sulfate (HS) proteoglycans. Heparanase is the sole mammalian enzyme with HS degrading endoglycosidase activity. Here, we aimed to ascertain whether heparanase plays a role in modulating the anabolic or catabolic responses of human articular chondrocytes. METHODS: Primary chondrocytes were incubated with pro-heparanase and catabolic and anabolic gene expression was analyzed by quantitative polymerase chain reaction (PCR). MMP13 enzymatic activity in the culture medium was measured with a specific fluorescent assay. Extracellular regulated kinase (ERK) phosphorylation was evaluated by Western blot. Human osteoarthritis (OA) cartilage was assessed for heparanase expression by reverse-transcriptase PCR, by Western blot and by a heparanase enzymatic activity assay. RESULTS: Cultured chondrocytes rapidly associated with and activated pro-heparanase. Heparanase induced the catabolic genes MMP13 and ADAMTS4 and the secretion of active MMP13, and down-regulated the anabolic genes ACAN and COL2A1. PG545, a HS-mimetic, inhibited the effects of heparanase. Heparanase expression and enzymatic activity were demonstrated in adult human osteoarthritic cartilage. Heparanase induced ERK phosphorylation in cultured chondrocytes and this could be inhibited by PG545, by fibroblast growth factor 2 (FGF2) neutralizing antibodies and by a FGF-receptor inhibitor. CONCLUSIONS: Heparanase is active in osteoarthritic cartilage and induces catabolic responses in primary human chondrocytes. This response is due, at least in part, to the release of soluble growth factors such as FGF2.

Inhibition of malignant thyroid carcinoma cell proliferation by Ras and galectin-3 inhibitors.

Anaplastic Thyroid carcinoma is an extremely aggressive solid tumor that resists most treatments and is almost always fatal. Galectin-3 (Gal-3) is an important marker for thyroid carcinomas and a scaffold of the K-Ras protein. S-trans, transfarnesylthiosalicylic acid (FTS; Salirasib) is a Ras inhibitor that inhibits the active forms of Ras proteins. Modified citrus pectin (MCP) is a water-soluble citrus-fruit-derived polysaccharide fiber that specifically inhibits Gal-3. The aim of this study was to develop a novel drug combination designed to treat aggressive anaplastic thyroid carcinoma. Combined treatment with FTS and MCP inhibited anaplastic thyroid cells proliferation in vitro by inducing cell cycle arrest and increasing apoptosis rate. Immunoblot analysis revealed a significant decrease in Pan-Ras, K-Ras, Ras-GTP, p-ERK, p53, and Gal-3 expression levels and significant increase in p21 expression levels. In nude mice, treatment with FTS and MCP inhibited tumor growth. Levels of Gal-3, K-Ras-GTP, and p-ERK were significantly decreased. To conclude, our results suggest K-Ras and Gal-3 as potential targets in anaplastic thyroid tumors and herald a novel treatment for highly aggressive anaplastic thyroid carcinoma.

A comparative roentgenographic analysis of the lumbar spine in male army recruits with and without lower back pain.

AIM: To determine whether there is an association between lumbar spine radiographic findings and reported current and/or past lower back pain (LBP). MATERIALS AND METHODS: Four hundred and sixty-four age-matched (mean age 18 years+/-2 months) consecutive male army recruits were examined. Half of them had a history of episodes of LBP. An orthopaedic evaluation (including radiographs of the lumbar spine) is part of the routine medical examination for all military recruits. Two senior orthopaedic surgeons and one radiologist who performed the morphological measurements assessed the radiographs. RESULTS: We found an increased frequency of right-sided scoliosis, lumbar lordosis, sacral lumbarization, wedge vertebra, bilateral spondylolysis of L5 and/or a sagittal diameter of less than 12 mm among the recruits with LBP. No such association was found with spina bifida, left-sided scoliosis, hemi-lumbarization, sacralization and hemi-sacralization, Schmorl's nodules or mild degenerative changes. CONCLUSION: Given that radiographic screening shows that LBP is more common in those with spinal deformity it may be a reasonable means of predicting which individuals are more likely to develop LBP.

The handheld dermatoscope as a nail-fold capillaroscopic instrument.

BACKGROUND: The presence of nail-fold capillary abnormalities may be useful in diagnosing several connective tissue disorders, including scleroderma, dermatomyositis, and mixed connective tissue disease, and in differentiating primary Raynaud phenomenon from Raynaud phenomenon due to scleroderma and mixed connective tissue disease. Capillaroscopy, however, usually requires special equipment and may be time consuming. Purpose To investigate the potential use of the unmodified common handheld dermatoscope as a capillaroscopic instrument. Subjects The study included 106 patients who were consecutively referred and a control group of 170 healthy subjects or patients with unrelated skin disorders. METHODS: A nail-fold capillaroscopic examination using a standard handheld dermatoscope was performed on all fingers of each subject. A scleroderma-dermatomyositis pattern was defined as the presence of 2 or more of the following findings in at least 2 nail folds: enlargement of capillary loops, loss of capillaries, disorganization of the normal distribution of capillaries, "budding" ("bushy") capillaries, twisted enlarged capillaries, and capillary hemorrhages (extravasates). RESULTS: A scleroderma-dermatomyositis pattern was found in 19 (70.4%) of 27, 7 (63.6%) of 11, and 4 (50%) of 8 patients with scleroderma, dermatomyositis, and mixed connective tissue disease, respectively. These frequencies were statistically significantly higher than a null percentage of scleroderma-dermatomyositis pattern in the control group (P<.001) and a scleroderma-dermatomyositis pattern in only 1 (4.5%) of 22 patients with systemic lupus erythematosus as well as in 2 (5.3%) of 38 patients with Raynaud phenomenon but without evidence of a connective tissue disorder (P<.01). CONCLUSIONS: The capillaroscopic results obtained with the dermatoscope are comparable to those described with other instruments. Therefore, the unmodified hand-held dermatoscope may be used as a capillaroscopic instrument to detect a scleroderma-dermatomyositis pattern and to help the dermatologist in the clinical diagnosis of connective tissue disorders.

Efficacy of closed wound drainage after total joint arthroplasty. A prospective randomized study.

The efficacy of closed suction drains following joint arthroplasty operations was prospectively evaluated in a randomized manner. All 88 patients allotted to primary knee or hip arthroplasty operations during a 6-month period were included in the study. Drains were used in 32 of 58 patients following total knee arthroplasty and in 18 of 30 total hip arthroplasties. No statistical difference was found in the hemoglobin levels measured following surgery and in the number of patients requiring blood transfusions between the two groups after total hip arthroplasty (P = .06). The power of the test to detect a difference of 2 g% in hemoglobin levels is 94%. Two patients from each group had a transient serous discharge for 3 to 4 days following surgery and none had wound infections. Significantly more blood transfusions were needed in patients with drains following total knee arthroplasty compared with patients without drains (0.7 unit per patient versus 0.2 unit per patient, P = .005) to maintain the same hemoglobin blood levels. Patients with no drains had significantly more transient sterile serous wound discharge than patients with drains (38.4% vs 12.5%, P = .02). Superficial wound infection necessitating antimicrobial medication developed in one patient with drains and in no patients in the other group. These results suggest that drains may not be needed following total hip arthroplasty. The more common serous wound discharge may be of some concern when drains are not used following total knee arthroplasty.

[Physical 3-dimensional testing of the lumbar spine using the IsoStation B-200].

Low-back pain is not only one of the major medical problems, but the most common. Up to 80% of the population is expected to experience back pain at least once in their lifetime. The functional disability caused by LBP has a major influence on quality of life, as well as its economic aspects. Psychological and social factors are highly involved with LBP. Therefore any advance in objective assessment of LBP is of major importance. We present a relatively new system used for the past 2 years by our departments, the IsoStation B-200 (Isotechnologies Co., NC). This system enables simultaneous 3-D measurements of range of motion, speed of movement and torques in the lumbar back in a highly accurate and reproducible manner. The results are used to classify the status of LBP in terms of severity and disability. They enable us to assess quality of performance and to detect the "symptom magnification syndrome" (SMS), patients with non-physiologic complaints and behavior. We describe in detail the measurement protocol and the exact definitions and criteria used in the process of patient classification. Finally we present the results of our first 238 patients tested. A highly significant difference in almost all measured and calculated parameters was found between the patients with physiologic behavior and those with SMS or nonphysiological behavior. Findings related to all classifications are presented.

Femoral notchplasty in the treatment of malunited intercondylar eminence fractures of the tibia.

A block of full extension may occur after malunion of an intercondylar tibial eminence fracture. Five patients with this complication were treated by arthroscopic femoral notchplasty. At follow-up, between 6 months and 5 years, four patients had regained full extension and the fifth was improved. This is an effective method of regaining extension in selected patients.

Levator scapulae syndrome: an anatomic-clinical study.

Twenty-two patients, all young females, presenting with a common clinical picture of pain over the upper medial angle of the scapula were studied. The dominant shoulder was the most commonly involved (82%). Pain radiated to the neck and shoulder, but rarely to the arm. Movements that stretched the levator scapulae on the affected side aggravated symptoms. Radiographs and bone scans of the shoulders and cervical spine were negative. Increased heat emission from the upper medial angle of the affected shoulder was found on thermography in more than 60% of the patients. Anatomic dissections of 30 cadaveric shoulders showed great variability in the insertion of the levator. A bursa was found between the scapula, the serratus, and the levator in more than 50% of the shoulders. This study suggests that this syndrome, leading to bursitis and pain, may be caused by anatomic variations of the insertion of the levator scapulae and origin of the serratus anterior. This may explain the constant trigger point and crepitation as well as the increased heat emission found on thermography. Local steroid injections relieved symptoms partially in 75% of those patients who underwent treatment.