Popliteal Artery Entrapment Syndrome.

¼ Popliteal artery entrapment syndrome is a commonly misdiagnosed condition that should be considered in patients presenting with exertional lower-extremity pain. ¼ In addition to a focused physical examination, the ankle-brachial index and advanced imaging consisting of computed tomography and computed tomographic angiography or magnetic resonance imaging and magnetic resonance angiography are crucial in evaluating the underlying cause of entrapment. ¼ Consultation with a vascular surgeon or team is necessary when planning surgical treatment of popliteal artery entrapment syndrome.

Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: a randomized controlled pilot trial (NCT00332254).

OBJECTIVE: To evaluate the clinical effectiveness of intraarticular IL-1 receptor antagonist (IL-1Ra) for anterior cruciate ligament (ACL) tear. METHODS: Eleven patients with acute ACL tear confirmed by magnetic resonance imaging (MRI) were randomized to receive a single intraarticular injection of IL-1Ra (anakinra 150 mg, n = 6) or equal volume of saline placebo (1 ml, n = 5). The double-blinded treatment was administered a mean 2 weeks after injury. Synovial fluid (SF) (n = 9 patients) and sera (all patients) were available at baseline (prior to injection) and immediately prior to surgery (mean 35 days later) and analyzed for SF IL-1α, IL-1ß, IL-1Ra and serum hyaluronan (HA), an indicator of synovial inflammation. The primary outcome, standardized Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, was obtained at 0 (baseline), 4, and 14 days after injection. RESULTS: Compared with placebo, the IL-1Ra group had substantially greater improvement in key outcomes over 14 days (KOOS pain P = 0.001; activities of daily living P = 0.0015; KOOS sports function P = 0.0026; KOOS quality of life (QOL) P = 0.0048; and total KOOS P < 0.0001). There were no adverse reactions in either group. SF IL-1α (P = 0.05) and serum HA (P = 0.03), but not IL-1ß, or IL-1Ra, decreased significantly in the IL-1Ra but not the placebo treated patients. Compared with placebo, IL-1α was borderline significantly different in the IL-1Ra treated group (P = 0.06). CONCLUSIONS: Administered within the first month following severe knee injury, IL-1Ra reduced knee pain and improved function over a 2-week interval. This promising proof of concept study provides a new paradigm for studies of acute joint injury and suggests that a larger follow-up study is warranted.

Global metabolic profiling of human osteoarthritic synovium.

Osteoarthritis (OA) is a debilitating disease associated with pain and loss of function in numerous diarthrodial joints of the body. Assessments of the severity and/or progression of OA are commonly based on radiographic stages and pain level, which aren't always correlated to severity of disease or joint dysfunction and may be confounded by other factors(1). There has been recent interest in identifying a biochemical signature of OA(1) that may be detected in serum, urine, and/or synovial fluid that would represent repeatable and predictable biomarkers of OA onset and/or progression. The objective of this study was to use global metabolic profiling to identify a distinct metabolic profile for cultured human synovial tissue from patients with end-stage OA compared to patients with little or no evidence of disease. While metabolic profiles from cultured tissues are not expected to reproduce in vivo profiles, it is expected that perturbations in metabolism caused by end-stage disease would result in differences in metabolic profiles in vitro compared to tissue with little or no evidence of disease. Because metabolomic perturbations often occur prior to alterations in the genome or proteome, metabolomic analysis possibly provides an earlier window to an altered biochemical profile for OA onset and/or progression, and may provide a unique set of potential drug targets. The synovium was targeted because it has been implicated in OA as a mediator of disease progression; osteoarthritic synovium has been demonstrated to express pro-inflammatory cytokines, such as Tumor Necrosis Factor - α (TNF-α), Interleukin-1 ß (IL-1ß), and IL-6(2), suggesting that a diseased synovial lining could produce an ideal set of biomarkers for diagnosing OA and/or monitoring disease progression. Media from the culture of synovial explants dissected from diseased human joints (early or end-stage OA) was subjected to global metabolic profiling with a liquid chromatography (LC)/and gas chromatography (GC)/mass spectrophotometry (MS)-based technology platform. Metabolites were identified by automated comparison of the ion features in the experimental samples to a reference library of chemical standard entries developed at Metabolon, Inc (Durham, NC). Global metabolic profiling resulted in the identification of 105 distinct compounds across all sample groups, with 11 compounds showing significantly different relative concentrations between end-stage and no/early disease groups. Metabolites specific to collagen metabolism, branched-chain amino acid metabolism, energy metabolism and tryptophan metabolism were amongst the most significant compounds, suggesting an altered metabolic state with disease progression.

Anterior cruciate ligament injuries in the female athlete.

With the participation of women in athletics growing rapidly over the last two decades, a disturbing gender-specific pre-disposition has emerged regarding anterior cruciate ligament (ACL) injuries of the knee. Female athletes have a two- to eightfold higher incidence of ACL injury than their male counterparts. It is estimated that 38,000 women sustain ACL tears per year. The majority of ACL injuries in female athletes occur through noncontact mechanisms, most often during deceleration activities, such as landing from a jump or cutting. The risk factors for noncontact ACL injuries can be categorized as intrinsic (anatomic and hormonal) and extrinsic (environmental and biomechanical). This article will discuss these risk factors that are thought to contribute to the higher incidence of ACL injuries in women, the development of prevention strategies, and the outcomes of ACL reconstruction in women.

Ankle chondral injuries and repair.

The success of cartilage repair in the ankle and other joints rests on multiple factors. Because native cartilage healing fails to produce hyaline, organized cartilage, the challenge lies in activating an appropriate healing response. The combination of an optimal structural matrix, infusion of pleuripotent cells, and gene-modified tissue engineering to activate an appropriate healing response appears most sensible. Until such technology is available for use in humans, however, autologous chondrocyte transplantation and osteochondral transfer procedures are attractive alternatives.

Association between ratio of matrix metalloproteinase-1 to tissue inhibitor of metalloproteinase-1 and local recurrence, metastasis, and survival in human chondrosarcoma.

Chondrosarcoma, a malignant cartilage-forming mesenchymal tumor, displays a wide range of clinical behavior that can be difficult to predict with histological analysis. Matrix metalloproteinases contribute to the processes of local invasion and metastasis by controlling the ability of a tumor to transverse tissue boundaries. The specificity of matrix metalloproteinase-1 (interstitial collagenase) for fibrillar collagen may be central to those processes. Matrix metalloproteinase-2 facilitates invasion by degradation of such basement-membrane structures as type-IV collagen. The balance between the activity of tissue inhibitors of metalloproteinase and the activity of matrix metalloproteinase determines the proteolytic activity and may, in part, determine the overall invasiveness and potential for metastasis. The measurement of the ratio of matrix metalloproteinase to tissue inhibitor of metalloproteinase may have prognostic value for determining whether individual chondrosarcomas are locally invasive or will metastasize. Furthermore, there may be a specific pattern of expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in chondrosarcomas that is related to local invasion and probability of metastasis. Sixteen paraffin-embedded archival specimens of tumors were examined. Six twenty-micrometer-thick sections were cut from each tumor, and the amounts of cDNA formed from the mRNA were determined with reverse transcription-polymerase chain reaction with use of novel primers for matrix metalloproteinase-1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2. The amounts of cDNA for the matrix metalloproteinases and their inhibitors were determined by chemiluminescence and band densitometry. The ratio of the amount of cDNA for matrix metalloproteinase-1 to that for its tissue inhibitor and the ratio of the amount of cDNA for matrix metalloproteinase-2 to that for its tissue inhibitor were calculated, and the results were compared with use of the Student t test, enabling log-rank analysis of Kaplan-Meier survival curves. These ratios as well as the age and gender of the patient; the grade, size, and location of the tumor; the type of adjuvant therapy; and the operative margins were examined for significance with use of stepwise logistic-regression analysis. The patients who had recurrent disease had a significantly higher (p < 0.003) ratio of matrix metalloproteinase-1 to tissue inhibitor of metalloproteinase-1 (mean, 0.939; range, 0.647 to 1.101) than the patients who were free of disease (mean, 0.703; range, 0.629 to 0.772). Moreover, there was a striking difference between the Kaplan-Meier survival curve associated with a high ratio (more than 0.8) and that associated with a low ratio (p = 0.0015). The mean ratio of matrix metalloproteinase-2 to tissue inhibitor of metalloproteinase-2 was 1.814 (range, 1.206 to 3.77) in the patients who had recurrent disease compared with 1.473 (range, 1.073 to 2.390) in those who were free of disease; this difference was not found to be significant, with the numbers available. Analysis of the survival curves indicated that a worse prognosis was associated with a high ratio, but again this relationship was not found to be significant. Regression analysis revealed that a high ratio of matrix metalloproteinase-1 to its tissue inhibitor was a moderately significant independent predictor of a poor outcome (alpha = 0.07).