The analysis of synovial fluid in total knee arthroplasties with flexion instability.

AIMS: Patients with flexion instability after total knee arthroplasty (TKA) often present with a recurrent effusion, which may be a haemarthrosis. While the radiographic factors contributing to flexion instability have been elucidated, the clinical diagnosis remains challenging. Our aim, in this study, was to determine the mean white cell count and differential profile in pre-operative aspirations of synovial fluid in a consecutive series of patients undergoing revision TKA for flexion instability. PATIENTS AND METHODS: Between 2000 and 2010, 60 patients undergoing aseptic revision TKA for flexion instability were identified. The results of the pre-operative aspiration of synovial fluid were available for 53 patients (88%). These patients were 1:2 matched to 106 patients who underwent aseptic TKA for indications other than flexion instability. The mean age of the patients at revision TKA was 65 years (44 to 82) and 55% were women. The mean follow-up was 4.3 years (2 to 10.2). RESULTS: In the flexion instability group, the median total cell count was 312 cells/µL (interquartile range (IQR) 104 to 624), with a mean distribution of 45% macrophages (2% to 90%), 30% lymphocytes (1% to 69%), 18% neutrophils (0% to 80%), 0.5% eosinophils (0% to 6%) and 7% other cells (0% to 42%; mainly synovial cells). There was no significant difference in the median total cell count (p = 0.14) or mean distribution of macrophages (p = 0.42), lymphocytes (p = 0.38), neutrophils (p = 0.19) and eosinophils (p = 0.89) between the flexion instability and control groups. There was a significant difference in the percentage of bloody serosanguineous aspirations which was 58% in the flexion instability group and 18% in the control group (odds ratio = 6.5; p = 0.0001). CONCLUSIONS: In the group of patients who underwent revision TKA for flexion instability, most had a mean cell count and differential similar to those who underwent revision for other aseptic indications. However, bloody serosanguineous aspirations were 6.5 times more common in those with flexion instability confirming that many of the recurrent effusions seen in this condition are haemarthroses. Cite this article: Bone Joint J 2017;99-B:1477-81.

[THE ROLE OF TRANSFORMING GROWTH FACTOR-B IN IMMUNOPATHOGENESIS OF DISEASES OF CONNECTIVE TISSUE].

The recent studies of molecular physiology of fibrillin and pathophysiology of inherent disorders of structure and function of connective tissue such as dissection and aneurysm of aorta, myxomatously altered cusps and prolapses of mitral valve, syndrome of hyper-mobility of joints, demonstrated that important role in development of these malformations play alterations of transfer of signals by growth factors and matrix cellular interaction. These conditions under manifesting Marfan's syndrome can be a consequence of anomalies of fibrillin-1 which deficiency unbrakes process of activation of transforming growth factor-ß (TGFß). The involvement of TGFß in pathogenesis of Marfan's syndrome permits consider antagonists of angiotensin-transforming enzymes as potential pharmaceuticals in therapy of this disease. The article presents analysis of publications' data related to this problem.

Ratio of T helper to regulatory T cells in synovial fluid and postoperative joint laxity after allograft anterior cruciate ligament reconstruction.

BACKGROUND: Arthroscopic anterior cruciate ligament (ACL) reconstruction with allograft may vary in instrumented laxity compared with autograft. T helper (Th) cells (CCR4+CCR6+Th) and regulatory T (Treg) cells are important in the early stage of immunologic reactions. It is unknown whether the ratio of CCR4+CCR6+Th to Treg is imbalanced and if it correlates with early postoperative laxity after ACL allograft reconstruction. We investigated the ratio and functional influence between these cells and the correlation with postoperative anterior knee laxity. METHODS: In 40 patients who experienced unilateral arthroscopy-assisted ACL reconstruction, the ACL graft was an allograft in 20 patients and autograft in 20 patients. Maximum manual anterior tibiofemoral laxity measurements were performed with arthrometry testing. The phenotypes of CCR4+CCR6+Th and Treg cells of peripheral blood and synovial fluid from the two patient groups were determined by flow cytometry. The functionality of isolated Treg cells and effector T cells was quantified in (3)H-thymidine proliferation assays. RESULTS: Both CCR4+CCR6+Th and Treg cells were significantly increased in the synovial fluid in the allograft group and were correlated with anterior knee laxity. The ratio of CCR4+CCR6+Th to Treg cells in the synovial fluid was positively correlated with laxity. Synovial CD4+CD25+ Treg cells displayed an increased suppressive capacity compared with blood CD4+CD25+ Treg cells. Activated responder T cells from the synovial fluid were less susceptible to CD4+CD25+ T cell-mediated suppression than were responder cells from blood. CONCLUSIONS: The ratio of CCR4+CCR6+Th to Treg cells in the synovial fluid was correlated with anterior laxity after ACL allograft reconstruction.

Are diagnostic criteria for general joint hypermobility and benign joint hypermobility syndrome based on reproducible and valid tests? A review of the literature.

OBJECTIVE: In this review we focus on current knowledge of the reliability of tests and diagnostic criteria for generalized joint hypermobility (GJH) and benign joint hypermobility syndrome (BJHS). METHODS: Currently, The British Society of Rheumatology recommends the Beighton scoring system. With this approach, GJH is judged present when 4 or more of 9 tests are positive. Curiously, only one inter/intrarater reproducibility study is available and it uses a cutoff level of 6, rather than the Beighton-recommended 4 positive tests. RESULTS: Using a 6 cut level, intra- and interobserver kappa scores were 0.75 and 0.78, respectively. Beighton scoring recommendations have been correlated with a global joint mobility index as well as with 2 other scoring systems, the Carter and Wilkinson, and the Rotès-Quérol. All illustrate high concurrent validity with one another. For the recently proposed Brighton criteria diagnosing BJHS no reproducibility studies exist. In the latter, the recommendations reflect high nosographic sensitivity and specificity while predictive values for positive test scores are poor. CONCLUSION: In general, the reproducibility of the various tests seems to be good, especially when performed by experienced rheumatologists.

[The influence of laser irradiation of low-power density on an experimental cartilage damage in rabbit knee-joints: an in vivo investigation considering macroscopic, histological and immunohistochemical changes]. / Der Einfluss von Laserlichtbestrahlung niedriger Leistungsdichte auf einen experimentellen Knorpelschaden im Kniegelenk des Kaninchens: eine in vivo-Untersuchung unter Berücksichtigung makroskopischer, histologischer und immunhistochemischer Veränderungen.

In a total of 45 rabbits, knee-joint arthrosis was induced according to the Hulth & Telhag model. Depending on the post-operative survival time, the cartilage was investigated macroscopically, histologically and immunohistochemically (within a period of 10 days to 8 months). Thereafter, the influence of laser irradiation at a wavelength of 692.6 nm and energy densities of 1 and 4 J/cm2 on the cartilage morphology seven days following the exposure was examined. After joint instability surgery it was found out that the cartilage changes in the main stress area (MSA) and in regions outside the main stress area (ROMSA) progressed differently. Various qualitative and semi-quantitative changes were found for collagens I, II, IV and V, and for the glycoproteins fibronectin and tenascin. Immunohistochemically, there was a growing expression of collagen I in the apical layers, collagen II showed a stronger pericellular expression, and collagen IV showed, after an initial growth of the pericellular expression, a reduced territorial expression and a stronger apical-interterritorial expression in the osteoarthrotic cartilage. For fibronectin, the cellular expression turned out to grow in the ROMSA. In the MSA it decreased, but at the same time the interterritorial expression grew. For Tanascin, there was a decrease of the interterritorial expression in the radial zone while the pericellular and interterritorial expression of the apical layers of the osteoarthrotic cartilage grew. Lasing proved to significantly influence the osteoarthrotically changed cartilage when applied at an energy density of 1 J/cm2, i.e., the morphological changes had not yet progressed to the extent the control group had. Both the chondrocyte density and the glucosaminoglycan content turned out to be higher. When lasing was applied at higher energy densities, no significant difference among the control groups was found. Thus, it could be demonstrated in vivo that an arthrotic process decelerates through the influence of laser light of low-energy densities.

The effects of hydroxyapatite coating and bone allograft on fixation of loaded experimental primary and revision implants.

We used our established experimental model of revision joint replacement to examine the roles of hydroxyapatite coating and bone graft in improving the fixation of revision implants. The revision protocol uses the Søballe micromotion device in a preliminary 8-week period of implant instability for the presence of particulate polyethylene. During this procedure, a sclerotic endosteal bone rim forms, and a dense fibrous membrane is engendered, having macrophages with ingested polyethylene and high levels of inflammatory cytokines. At the time of revision after 8 weeks, the cavity is revised with either a titanium alloy (Ti) or a hydroxyapatite (HA) 6.0 mm plasma-sprayed implant, in the presence or absence of allograft packed into the initial 0.75 mm peri-implant gap. The contralateral limb is subjected to primary surgery with the same implant configuration, and serves as control. 8 implants were included in each of the 8 treatment groups (total 64 implants in 32 dogs). The observation period was 4 weeks after revision. Outcome measures are based on histomorphometry and mechanical pushout properties. The revision setting was always inferior to its primary counterpart. Bone graft improved the revision fixation in all treatment groups, as also did the HA coating. The sole exception was revision-grafted HA implants, which reached the same fixation as primary Ti and HA grafted implants. The revision, which was less active in general, seems to need the dual stimulation of bone graft and HA implant surface, to obtain the same level of fixation associated with primary implants. Our findings suggest that the combination of HA implant and bone graft may be of benefit in the clinical revision implant setting.

Magnetic resonance imaging confirmation of resolution of periodontoid pannus formation following C1/C2 posterior transarticular screw fixation.

Chronic odontoid fractures are considered unstable spinal lesions. Chronic instability in this region leads to the development of an inflammatory pannus, which can progress resulting in spinal cord compression radiographically and a myelopathy syndrome clinically. In this report we document three cases of reversal of pannus after C1/C2 transarticular screw fixation of an unstable odontoid fracture. Three patients were identified with chronic odontoid fractures and spinal cord compression due to periodontoid pannus formation. All patients presented with a progressive myelopathy syndrome. All patients underwent preoperative and postoperative magnetic resonance imaging (MRI) of the craniovertebral junction. C1/C2 transarticular screw fixation was performed for stabilization of C1/C2. Postoperatively there were no complications. Postoperative MRI at 6 months demonstrated resolution of the ventral pannus. Moreover, all patients exhibited improvement of preoperative neurological deficits. MRI is the imaging technique of choice for diagnosis and follow-up of patients with chronic odontoid fractures and ventral pannus. C1/C2 transarticular screw fixation provides a viable method for spinal stabilization in this region. In addition, stabilization can result in resolution of inflammatory pannus formation secondary to instability of the C1/C2 articulation.

Pro-inflammatory interleukins in the synovial fluid of rheumatoid arthritis associated with joint hypermobility.

BACKGROUND: Joint hypermobility (JH) is frequently seen in rheumatology; in some cases, such as rheumatoid arthritis (RA), it may represent a worsening of disease evolution. The aim of our study was to evaluate the influence of joint hypermobility on RA synovial fluid (SF) inflammation. Patients and methods. One hundred consecutive adult patients with RA and joint effusion of the knee were examined for the presence of JH. In the SF we evaluated volume, the number of white blood cells (WBC) and the levels of interleukin (IL)-1beta, IL-6 and IL-8 and prostaglandin E2 (PGE2). RESULTS: JH was associated with RA (JH-RA) in 18 patients, all of whom were female. Compared with non-JH RA, all the SF indices found in JH-RA were higher, although significant differences were observed only for volume, IL-8 and PGE2. CONCLUSION: In JH-RA, increased joint mobility seems to be associated with a more severe local inflammatory response, which may contribute to the more erosive evolution observed in our patients.

Ultrasonographic, axial, and peripheral measurements in female patients with benign hypermobility syndrome.

Twenty-five female Caucasians, aged 19-57 years, with the hypermobility syndrome had bone density measurements using established noninvasive techniques such as dual X-ray absorptiometry (DXA), single photon absorptiometry (SPA), heel ultrasound (US), and peripheral computed tomography (pQCT) acquisitions of the radius. As a group, comparisons of the different bone indices with the corresponding age-matched reference population resulted in normal z-scores for the arial densities, however, values for the volumetric total and cortical bone at the radius measured by pQCT were significantly lower than expected (P < 0.0001). Spinal and femoral bone density results were significant after correction for body mass index (BMI). This cross-sectional study shows that the benign hypermobility syndrome patients have lowered t-scores for data reflecting bone structure and bone strength as measured with US and the tomographic technique.

High macrophage-colony stimulating factor levels in synovial fluid of loose artificial hip joints.

OBJECTIVE: To clarify a macrophage-colony stimulating factor (M-CSF) related mechanism of aseptic loosening of artificial hip joints. METHODS: Synovium-like interface tissues between bone and prosthesis, regenerated pseudocapsular tissues, and synovial fluid (SF) were collected from 9 patients with loose artificial hip joint at revision surgery. Tissue distribution, production site, and SF level of M-CSF in loose hip joints were investigated by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and ELISA, respectively. For a comparative assessment of the M-CSF level in loose hip joints, SF of active rheumatoid arthritis (RA) and mild osteoarthritis (OA) also were analyzed by ELISA. RESULTS: Immunohistochemical analysis showed the presence of M-CSF immunoreactive cells mainly in the interface tissues between bone and prosthesis and inner pseudocapsular tissues, both of which were in contact with joint fluid. RT-PCR analysis confirmed the local production of M-CSF in these periprosthetic tissues. Significantly higher M-CSF level in loose hip joint fluid than in active RA and mild OA fluid was revealed by ELISA. CONCLUSION: High M-CSF level in loose hip joint fluid suggests transportation of M-CSF from production sites to joint fluid. This indicates that not only polyethylene wear particles (reported to induce foreign body reaction at the bone-prosthesis interface), but also M-CSF, abundant in joint fluid, are transported to and affect the interface. Thus, M-CSF is locally produced in periprosthetic tissues of loose hip joints and possibly contributes to periprosthetic weakening and osteolysis via joint fluid, leading to prosthetic loosening.

Total joint arthroplasty and the immune response.

Total joint replacement arthroplasty has proved highly successful in the management of osteoarthritis and rheumatoid arthritis. The cause of aseptic loosening of prosthetic joint replacement components is unclear. Early experience with total joint arthroplasty was plagued by a number of problems that no longer exist as major impediments to long-term success. Improvement in the operating room environment and the use of prophylactic antibiotics have substantially reduced the high incidence of infection to less than 1%. Implant materials have long been considered biologically inert, but recent studies indicate that inflammatory reactions directed against the implanted materials may contribute to aseptic loosening. Currently, particulate debris from cement or polyethylene causing loosening of the prosthesis is the major problem in total joint arthroplasty. Significant data suggest a progression from a simple inflammatory reaction to complex immune responses against the biomaterials. The cellular responses to particles of polymethylmethacrylate, ultra-high-molecular-weight polyethylene, and alloys of cobalt-chromium and titanium have been assayed in vitro in patients with osteoarthritis, rheumatoid arthritis, and avascular necrosis who had total joint replacement. Elevated immunologic cell proliferation responses to both acrylic and cobalt chromium were observed in patients with aseptically loosened prostheses. These findings suggest that the development of a cellular response to particulate debris may be significant in the pathogenesis of aseptic loosening.

Immunohistochemical analysis of 3-B-(-) and 7-D-4 epitope expression in canine osteoarthritis.

OBJECTIVE: To examine the distribution of the 3-B-3(-) and 7-D-4 epitopes in proteoglycans from morphologically normal and osteoarthritic (OA) canine articular cartilage. METHODS: Cartilage samples from the femurs of stable and destabilized stifle joints of 9 dogs that had undergone transection of the cranial cruciate ligament were examined by immunohistochemistry. RESULTS: The 3-B-3(-) and 7-D-4 epitopes were expressed in the superficial zone of cartilage from the destabilized femorotibial joints in the early stages of developing OA. The staining patterns with these two antibodies differed, with 3-B-3(-) reactivity confined to the superficial and upper middle zones of the articular cartilage, and 7-D-4 reactivity more prominent in the matrix, extending into the deeper zones and increasing with progression of the lesion. Both epitopes were also expressed in the superficial and upper middle zones of areas peripheral to the lesions and were detectable before the loss of matrix and proteoglycans could be identified by histochemical staining with toluidine blue. CONCLUSION: In this study, the expression of atypical chondroitin sulfate proteoglycans was demonstrated in osteoarthritic canine cartilage, and the pattern of expression changed as the lesions progressed. The occurrence of 3-B-3(-) and 7-D-4 epitopes appears to be associated with changes in chondrocyte metabolism in the early stages of cartilage degeneration in experimental osteoarthritis.

[Juvenile ankylosing spondylitis and the joint hypermobility syndrome]. / Juvenilni ankilozirajuci spondilitis sa sindromom hipermobilnosti zglobova.

The problem of correlation of rheumatic diseases with mobility of joints in children and young individuals was not frequently been considered. The first of a few authors was C.J. Sutro who was concerned with this problem in 1947. The goal of our treatment was to prevent as long as possible the onset of ankylosis in our patients. They were treated by NSAID as well as by intensive kinesi- and hydrotherapy. All these patients, besides HLA-B27 have also A2 antigen, a possible gen for hypermobility. A prospective study should explain the significance and role of A2 antigen in these patients.

A subluxing arthropathy associated with the anti-Jo-1 antibody in polymyositis/dermatomyositis.

Of 180 patients with polymyositis/dermatomyositis (PM/DM) seen at the University of Pittsburgh and affiliated hospitals since 1975, 21 of 100 tested positive for the anti-Jo-1 antibody. Sixteen of the 21 patients were women and 18 were white. Fifteen had adult PM, 4 had myositis in overlap with scleroderma, and 2 had adult DM. Evidence of interstitial lung disease was found in 12 of 18 anti-Jo-1 positive patients (67%), but in only 15 of 79 anti-Jo-1 negative patients (19%) (P less than 0.0002). The 21 anti-Jo-1 positive patients were divided into 3 separate groups based on the observed articular findings. Four patients had a deforming, predominantly nonerosive arthropathy with subluxations of the distal interphalangeal joints, especially the thumbs. Eight patients had a nondeforming arthropathy primarily affecting the small joints of the hands, wrists, shoulders, and knees. Those with deformities had a longer duration of arthritis compared with those with nondeforming arthropathy (mean 14.5 years versus 3.3 years). Nine anti-Jo-1 positive patients had no joint arthropathy. Three of 4 patients with deformities have required articular reconstructive surgery for subluxation, with 2 having associated subcutaneous calcinosis.