Septic Joint Disease Research Articles

Synovial Fluid D‐Dimer Concentration in Foals with Septic Joint Disease

Increased synovial fibrinolytic activity (detected by increases in synovial D-Dimer concentrations) has been observed in different joint diseases in humans and adult horses, presumably in order to minimize fibrin deposition within the joint and thus avoid its detrimental effects. To investigate fibrinolytic pathway activation in joint sepsis in foals by measuring synovial D-Dimer concentrations. Eighteen septic foals with septic joints, 9 septic foals without septic joints, 9 systemically healthy foals with septic joint, and 3 controls are included. Prospective observational clinical study of foals admitted for septic arthritis. Synovial D-Dimer concentration and routine synovial fluid analysis were performed. Diagnosis of joint sepsis was made whenever synovial total nucleated cell count was >30,000 cells/μL, synovial total protein >4 g/dL, and neutrophil percentage of >80%, or synovial fluid culture resulted positive. Results were compared among groups by general lineal models. Synovial D-Dimer concentration was significantly (P < .001) higher in the foals with septic joints compared with foals without joint disease (P < .001). Septic joint disease is associated with a marked increase of synovial D-Dimer concentration (marked activation of the fibrinolytic activity) within the affected joint. Although further studies are needed, the measurement of synovial D-Dimer concentration may be considered a complementary diagnostic marker of septic joint disease.

TLR‐2‐mediated induction of vascular endothelial growth factor (VEGF) in cartilage in septic joint disease

Bacterial arthritis is a progressive joint disease which includes rapid destruction of articular cartilage even after clearance of the causal factor. The resulting post-infectious arthropathy is mainly characterized by self-perpetuating joint destruction and extensive angiogenesis in the emerging pannus-like synovial membrane, but the underlying molecular mechanisms of the bacteria-initiated process remain incompletely understood. This study was conducted to elucidate the expression and regulation of angiogenic and cartilage-destructive vascular endothelial growth factor (VEGF) in septic arthritis. For that purpose, aspirates of synovial fluid from patients with pyogenic arthritis were examined for VEGF levels by ELISA. In vitro studies with primary and immortalized chondrocytes were performed to determine whether Gram-positive and Gram-negative bacteria induce VEGF expression, by using real-time RT-PCR, ELISA, and immunohistochemistry. Activation of the transcription factor AP-1 was assessed by EMSA experiments. The necessity of the Toll-like receptor-2 (TLR-2), ERK-1/-2, and AP-1 pathway for infectious VEGF induction in chondrocytes was examined by using specific blocking reagents. ELISA experiments revealed that aspirates of synovial fluid from patients with pyogenic arthritis contain elevated levels of VEGF. The in vitro results confirmed the transcriptional induction of VEGF in chondrocytes after bacterial challenge by real-time RT-PCR, ELISA, and immunohistochemistry. This activation was mediated by a TLR-2-, ERK-1/-2-, and AP-1-dependent pathway. The findings demonstrate the expression of Toll-like receptors on mesenchymal articular chondrocytes and reveal TLR-2-mediated VEGF induction in human chondrocytes after Gram-positive bacterial sensing. Since VEGF is a potent angiogenic and tissue remodelling factor, evidence that Toll-like receptors contribute to destructive arthropathy after microbial joint infection is provided. VEGF may be a therapeutic target in the future for the prevention of post-infectious cartilage degradation in articular joints.

Measurement of cartilage oligomeric matrix protein (COMP) in normal and diseased equine synovial fluids

Objective This study was designed to assay cartilage oligomeric matrix protein (COMP) in equine synovial fluids and to compare the concentration in synovial fluids from normal horses with joint diseased horses. The relationship between the COMP degradation and the matrix metalloproteinase activity in synovial fluids was also investigated.Design Using COMP antigen prepared from equine articular cartilage and murine monoclonal antibody (12C4) raised against human COMP, an inhibition ELISA was developed. COMP in equine synovial fluids from normal and diseased joints was quantified. Metalloproteinase activities were evaluated in the same synovial fluids by a gelatin degradation ELISA. COMP fragments were evaluated qualitatively by Western blotting.Results The COMP inhibition ELISA was reliable at concentrations of equine COMP between 62.5 and 2000ng/ml. COMP values in joint fluids in both aseptic and septic joint disease (19.7±15.3 and 16.1±11.2μg/ml, respectively) were significantly (P< 0.001) lower than normal (53.2±29.0μg/ml). The molecular sizes of COMP on immunoblots were different between normal and diseased synovial fluids; more fragments were seen in diseased fluids. The aseptic (26.6±20.6%) and septic joint disease synovial fluids (36.1±37.5%) had significantly higher (P< 0.02 and 0.002, respectively) gelatinolytic activities than normal (13.6±13.7%). There was a negative correlation (R=−0.31, P< 0.002) between COMP level and gelatinase activity.Conclusions We conclude that the fragment pattern and the absolute COMP concentration maybe useful for monitoring joint disease, and that COMP degradation in synovial fluids from progressed joint disease may be due to MMP gelatinolytic activity.

Matrix metalloproteinases 2 and 9 activity in bovine synovial fluids.

Matrix metalloproteinases (MMPs) are important enzymes found in connective tissues and thought to be involved in cartilage degradation. They are detectable in bovine synovial fluid and may play a destructive role in bovine septic arthritis. The MMP gelatinase enzymes were detected by gelatin zymography using image analysis of the gels. The active gelatinase levels were determined by a gelatin degradation enzyme-linked immunosorbent assay (ELISA). Increased concentrations of MMP-9 activity were found in the synovial fluids of cows with septic arthritis (P < 0.001) in comparison with fluids from normal joints. Using the gelatin degradation ELISA the net active gelatinases were measured, and significant increases were found in gelatinase bioactivities in synovial fluids from septic joint disease cases (P < 0.001). Increased concentrations of MMP-2 activity were found in the synovial fluids of cows with aseptic arthritis, which appeared to be playing an important role in degradation of articular cartilage in joint disease. This finding required further investigation.

The differential diagnosis of benign and septic joint disease in children. Clinical, radiologic, laboratory, and joint fluid analysis, based on 37 children with septic arthritis and 97 with benign aseptic arthritis.

The differential diagnosis of benign and septic joint disease in children. Clinical, radiologic, laboratory, and joint fluid analysis, based on 37 children with septic arthritis and 97 with benign aseptic arthritis.

UCLA Conference. Diagnosis and treatment of erosive rheumatoid arthritis and other forms of joint destruction.

Single or multiple destruction of joints arises from many causes, ranging from the acute destructive process (usually monarticular) in septic joint disease to the chronic, slowly evolving destruction of cartilage and adjacent bone that occurs in osteoarthritis. Medical treatment of a few of these conditions (including rheumatoid arthritis) is reasonably satisfactory if it is initiated early. On the other hand, surgical procedures are indicated if physical and X-ray examination of the involved joints discloses the presence of a significant destructive process involving both articular cartilage and bone. Several very satisfactory such operative techniques, including synovectomy (in the relatively early phases) and prosthetic joint replacement, have been recently developed. These are especially favorable in destructive disease of the hip, knee, or small joints of the hand. The various differential diagnostic, radiographic medical, and surgical procedures are discussed in some detail in this conference.

Antibiotic concentrations in septic joint effusions.

Abstract Fifty specimens from 27 infants and children with septic joint disease were assayed for ampicillin (18 specimens), methicillin (14 specimens), penicillin (14 specimens) or cephalothin (four specimens). The ranges of observed values varied depending upon the dose and the interval after administration. The joint-fluid level was the same as or higher than the serum level in eight of nine paired specimens tested for ampicillin and in seven of 11 paired specimens assayed for methicillin. Comparable serum and joint-fluid levels of penicillin were found in 11 of 12 paired specimens. The four antibiotics studied enter joint fluid in concentrations greatly in excess of in vitro inhibitory levels of the usual bacteria that cause septic arthritis. There is no need for intra-articular administration. Intramuscular therapy appears as effective as the intravenous route with ampicillin and probably with methicillin and penicillin.

Acute infectious arthritis in the aged and chronically ill.

Acute infectious processes of all types stand out as potentially lethal complications in the aged and in the chronically ill, and acute septic arthritis is not a rare form of infection in the older age groups—especially in those persons who have underlying chronic disorders. Since the host-response to infections in this group is notoriously atypical, the recognition of septic joint disease depends primarily upon the diligence with which it is sought. Ten cases of acute septic arthritis have been seen in an 18-month period at King County and Seattle Veterans Administration Hospitals, a case load casting doubt on the notion that acute septic joint disease was to become a medical curiosity. 1 A retrospective study of three and one-half years' experience in the same hospitals yielded nine additional patients in whom pyarthrosis had been established. Thus, a total of 19 cases was seen over a period of five years. The

Septic joint disease: Report of four cases of hip joint involvement

Septic joint disease: Report of four cases of hip joint involvement

Healing in Bone Tuberculosis

THE method of healing in any infection of a joint in which there has been bony destruction may be primarily classified under two heads: 1. By fibrous union or replacement of eroded bones and cartilage by connective tissue; 2. By new bone formation in and about the joint. In this article we wish to consider only that class in which there is demonstrable new bone formation during the stage of repair. In arthritis deformans and in purulent involvement of joints, it is recognized that there is usually quite marked new bone formation during the stage of healing; also in tuberculous joints in which there has been sinus formation, with consequent invasion by secondary organisms. It has been taught that there is never, or rarely, new bone formation in the repair of tuberculous joints other than in cases in which there are complications, as sinus formation and resulting secondary infection. Baetjer and Waters, in the text, “Injuries and Diseases of Bones and Joints,” make the statement that there is no new bone formation in tuberculosis. This premise is used to differentiate tuberculosis of the spine from various non-tuberculous diseases and also to differentiate tuberculosis from compression fracture. Jones and Lovett in their text, “Orthopedic Surgery,” in describing arthritis deformans, say that loss of the intervertebral space, accompanied by lipping and spur formation on the edges of the vertebræ, is pathognomonic of arthritis deformans. We have frequently seen these identical findings in proven cases of Pott's disease. Cofield, in 1922, called attention to “bony bridging in tuberculosis of the spine.” Our experience corresponds with his, and we have found that not infrequently do we see quite extensive new bone formation in the repair of joint tuberculosis in cases in which there have been no communicating sinuses, with secondary infection. In our experience it has also been noted that healing by production of osseous tissue is more prevalent in tuberculosis of the vertebræ than in hip or sacro-iliac involvement. About 15 per cent of our cases of Pott's disease have demonstrable new bone formation during the stage of healing. The differential diagnosis from an X-ray standpoint, between tuberculous joints, arthritis deformans, and some cases of Septic joint disease, must occasionally lie, then, in the appreciation of secondary findings, as, for instance, Presence of paravertebral abscess; Presence of accompanying pulmonary tuberculosis. Conclusions Tuberculosis of the joints and spine is frequently accompanied by definite bony bridging. This finding is much more common in the spine than in the joints. The presence of certain accompanying changes is occasionally necessary to warrant a positive diagnosis of Pott's disease.