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Biomedical subjects

E Bogoch

Publications and source records attributed to E Bogoch.

At least 19 recordsLinked to original sources

The radioulnar ratio: a new method of quantifying distal radioulnar joint subluxation.

Computed tomography was used to image the distal radioulnar joint (DRUJ) for instability. Four methods were used to quantify subluxation of the DRUJ: the Mino criteria, the epicenter method, the congruency method, and a new method called the radioulnar ratio (RUR). Validity of the various methods was evaluated in clinical and laboratory situations. Rheumatoid patients with symptomatic DRUJ pathology had significantly more abnormal RUR values (100% vs 73% [epicenter method] and 88% [Mino criteria]). The RUR detected instability sooner in a progressive laboratory-induced instability model. The intraobserver and interobserver reliability of the RUR was high, with intraclass correlation coefficients of 0.89 and 0.87, respectively. The RUR demonstrated superior performance in the diagnosis of DRUJ subluxation.

Adult↗

Outcomes of symptomatic osteonecrosis in 95 patients with systemic lupus erythematosus.

OBJECTIVE: To describe the frequency and type of symptomatic osteonecrosis (ON) in a large cohort of patients with systemic lupus erythematosus (SLE) followed in a single center and to describe the outcome in terms of mortality and disability compared to SLE patients without ON. METHODS: Patients with ON were identified from the University of Toronto Lupus Clinic Database. The diagnosis of ON was confirmed by radiographs, bone scans, tomograms, or magnetic resonance images. A comparison group of patients with SLE without ON was selected from the same database, matched by year of birth, sex, and year of entry to the clinic. Mortality, disability, and health related quality of life were compared between patients with and without ON. RESULTS: Ninety-nine patients with ON were identified with 217 affected joints, the majority hips and knees, often in a bilateral distribution. There was no increase in mortality. Patients with ON had higher Health Assessment Questionnaire scores and lower SF-20 scores of physical functioning, suggesting increased disability. Hip joints that underwent surgery were more likely to have higher grades of ON at diagnosis. CONCLUSION: Symptomatic ON occurred in 12.8% of 744 patients with SLE and often involved multiple joints. ON was not associated with increased mortality but was associated with physical disability. Radiological class of the hip jointsat diagnosis of ON was predictive of subsequent surgery.

Adolescent↗

Cementless acetabular fixation in total hip arthroplasty using polyglycolide-lactide screws: an in vivo canine study.

Bone ingrowth into cementless acetabular components was evaluated in a canine total hip arthroplasty model, comparing components initially stabilized with polyglycolide-lactide screws with those initially stabilized with titanium screws. The acetabular shell was anchored with 2 polyglycolide-lactide screws in 16 dogs and with 2 titanium screws in 12 dogs. The dogs were followed and sacrificed at 7 weeks, 14 weeks, 10 months, or 15 months. Histomorphometric analysis of bone ingrowth into the weight-bearing dome of the acetabular shell was conducted. No difference was detected in mean bone ingrowth into the acetabular shell comparing the 2 screw groups. The results of this study do not support a significant advantage to the use of biodegradable screws for the initial stabilization of cementless acetabular components in canine total hip arthroplasty.

Acetabulum↗

Radiographic reports in osteonecrosis of the hip in systemic lupus erythematosus.

The purpose of this study was to assess the reliability and accuracy of the modified Marcus and Enneking classification of osteonecrosis of the femoral head in patients with systemic lupus erythematosus when applied to the reading of the original radiographs and then applied to interpreting the radiologist's written report. Thirty anteroposterior radiographs of the hip from patients with systemic lupus erythematosus with varying degrees of osteonecrosis were selected and submitted to a panel of two rheumatologists and an orthopaedic surgeon who individually graded the radiographs using the modified Marcus and Enneking method. Agreement was determined by the kappa statistics. Identical staging was assigned in 21 of the 30 radiographs by all three observers, providing a weighted kappa of 0.88. Identical staging was assigned by all three observers in 26 of the 30 reports, giving a kappa of 0.95. There was agreement in the staging of 23 of the 30 radiographs by actual reading and the radiologist's report, with a weighted kappa of 0.86. Discordant gradings resulted primarily because the Marcus and Enneking method does not account for degenerative changes on the femoral side of the hip joint. The authors conclude that the radiologist's report can be used to stage osteonecrosis when interpreted by expert observers and when those reports contain all critical information required for staging. The authors recommend that the Marcus and Enneking classification be modified to include changes on the femoral side of the joint.

Femur Head Necrosis↗

Contents and distributions of the proteoglycans decorin and biglycan in normal and osteoarthritic human articular cartilage.

The study was designed to determine the contents and distributions of the proteoglycans decorin and biglycan in adult human femoral condylar cartilage and whether these may change in osteoarthritis. New radioimmunoassays were established using peptides representing the amino-terminal 21 amino acid sequence of each proteoglycan (to which a tyrosine was added for radioiodination) and antibodies in a rabbit antiserum raised to both these molecules. Cartilage was extracted with 4 M guanidine HCl to determine total content, and extracts were analyzed by chromatography to determine molecular sizes. Frozen sections were cut parallel to the articular surface and were extracted to determine distribution within the tissue. Gel chromatography on Sepharose CL-2B under dissociative conditions revealed molecules with a partition coefficient of 0.7-0.75 in both normal and osteoarthritic cartilage. In normal adult cartilage, the mean contents of the core proteins of biglycan and decorin were calculated to be approximately 0.34 and 0.48 mg per gram wet weight, respectively. These represented molar contents similar to that of aggrecan. In osteoarthritic cartilage, there were no overall significant changes in the content and distribution of these molecules. There was, however, considerable individual variation in both distribution and content. Analyses indicated that there was a trend in osteoarthritic cartilage toward a loss of biglycan and decorin from the more superficial layers of intact cartilage, where both these molecules are normally more concentrated. This was accompanied by maintenance of proteoglycan content deeper in the cartilage, regardless of the degree of degeneration.

Adult↗

Induction of release of secretory nonpancreatic phospholipase A2 from human articular chondrocytes.

OBJECTIVE: Secretory nonpancreatic phospholipase A2 (sPLA2) is a known inducer/promoter of the inflammatory process in the joints. It correlates with disease activity in adult and juvenile rheumatoid arthritis. Synovial fluids contain high concentrations of sPLA2. We discovered that human articular cartilage contains large quantities of sPLA2 and that culture chondrocytes constitutively synthesize and release sPLA2. To test the mechanism controlling the release of sPLA2, we exposed cultured human articular chondrocytes to cytokines and other agents, known to induce sPLA2 in other cells. METHODS: Chondrocytes obtained from cartilage of normal appearance from rheumatoid and osteoarthritic joints, and from normal, neonatal joints were compared to rabbit articular chondrocytes. Radiolabeled Escherichia coli derived phospholipid assay and ELISA technique using monoclonal antibodies against recombinant human synovial type sPLA2 were employed. The cells were grown as monolayers as well as in alginate beads. RESULTS: Human articular chondrocytes from both arthritic and neonatal joints released sPLA2 constitutively but could not be further stimulated with interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), IL-6, oncostatin M, lipopolysaccharide (LPS), or forskolin. Marked stimulation was observed when the cells were exposed to 8-bromo cyclic adenosine monophosphate (cAMP). Growing the cells as monolayers or in alginate beads did not change the results. In contrast to human cells, rabbit chondrocytes responded to IL-1 beta and IL-1/TNF, but not to TNF-alpha alone, with a very marked increase in extracellular sPLA2 activity. CONCLUSION: Human articular chondrocytes synthesize and constitutively release sPLA2. Such continuous release is most probably responsible for the high concentration of sPLA2 in articular cartilage and may be the source of synovial fluid sPLA2. To our knowledge, human articular chondrocytes are the only sPLA2 producing cells tested to date that do not respond to cytokine stimulation with increased sPLA2 activity; yet enhancement was seen with 8-bromo cAMP. It seems therefore that, human articular chondrocytes possess signalling mechanisms for the release of sPLA2 unlike those from other mammalian cells. The significance of this observation remains to be elucidated.

8-Bromo Cyclic Adenosine Monophosphate↗

Reliability and validity of the grading of heterotopic ossification.

The purpose of this study is to assess the reliability and validity of the Brooker grading of heterotopic ossification. Anteroposterior hip radiographs of 77 patients, taken 6 months following total hip arthroplasty, were blindly evaluated twice by two surgeons using the Brooker scale. Patients were also evaluated with the Harris hip scale, and range of motion of the hip was determined. All inconsistencies in heterotopic ossification grading were reviewed by the same two surgeons who developed six points of clarification to minimize ambiguities in the Brooker grading criteria. A second set of 76 radiographs were reviewed by the two surgeons using this modified Brooker index. The intraobserver reliability of the two readers was good, with agreements of 77 and 86% and weighted kappa values of 0.63 and 0.69, respectively. The two surgeons demonstrated fair interobserver reliability on the first reading (agreement of 68% and weighted kappa of 0.57) that improved to a good level of reliability (agreement of 77% and weighted kappa of 0.68) using the revised Brooker index. The grade of heterotopic ossification was correlated (r = -.25, P = .005) with the aggregate range of hip motion, but had no relationship to the patient's Harris rating. In conclusion, the grading of heterotopic ossification is reliable. Although the severity of heterotopic ossification did not correlate with the Harris scale, the relationship between heterotopic ossification and range of motion indicates that the Brooker index is also a valid measurement.

Hip Joint↗

Healing of cancellous bone osteotomy in rabbits--Part I: Regulation of bone volume and the regional acceleratory phenomenon in normal bone.

We performed a simple, undisplaced, incomplete osteotomy of the distal medial condyle of mature New Zealand White rabbits and permitted healing without fixation for 4 weeks. During the recovery period, the rabbits received the bone label calcein in their drinking water. From ground stained and unstained sections, we determined histomorphometric parameters in five zones: osteotomy gap, juxtaosteotomy, lateral condyle, metaphysis, and diaphysis. At 4 weeks, newly formed cancellous bone had obliterated the osteotomy gap. Osteotomy also stimulated new bone formation in cancellous bone of the medial condyle around the osteotomy. At that site, we found a fivefold increase in new bone without a change in bone volume (BV). Stimulation of bone formation was not observed in cancellous bone of the lateral condyle that had not been operated on or in cortical bone of the metaphysis or diaphysis. The maintenance of BV, despite increased new bone formation in the osteotomized medial femoral condyle, was probably due to a local acceleration of bone remodeling.

Animals↗

Healing of cancellous bone osteotomy in rabbits--Part II: Local reversal of arthritis-induced osteopenia after osteotomy.

With use of the intravital bone label calcein, we previously identified, by histomorphometry, greatly increased new bone formation and juxtaarticular osteopenia (a high turnover state) in carrageenan-induced experimental inflammatory arthritis of the knee in rabbits. In Part I of this paper, we showed that a large increase in new bone formation after a stable incomplete distal femoral condylar osteotomy of normal bone in the rabbit does not increase bone volume (BV) in normal tissue adjacent to the osteotomy (zone 1). In this study, we performed an osteotomy of bone made osteopenic by experimental inflammatory arthritis. After 4 weeks of healing, we examined new bone formation and BV in five zones around the osteotomy. In zone 0 (the osteotomy gap), new bone formation filled the gap to normal BV, as we found for the normal/osteotomy group. In zone 1 (adjacent to but excluding the osteotomy gap), we found greatly increased new bone formation and a return to normal BV, increased from the osteopenic level induced by experimental inflammatory arthritis. In this model, osteotomy apparently reversed the bone-wasting process of inflammatory arthritis. This effect was not observed in other zones: the lateral condyle that had not been operated on, the metaphysis, or the diaphysis.

Animals↗

Osteoarthritis in the human knee: a dynamic process of cartilage matrix degradation, synthesis and reorganization.

The matrix of articular cartilage undergoes degenerative changes in osteoarthritis which involve a number of matrix molecules. The structural and mechanical integrity is organized around the composite collagen II, IX, XI fibrillar organization. The small proteoglycan decorin that binds to these fibrils may influence their structure and mechanical properties. Aggrecan interacts indirectly via hyaluronic acid and possibly directly through unknown mechanisms. When collagen is cleaved at the articular surface in early osteoarthritis, decorin and aggrecan are lost. Increases in decorin and aggrecan content occur deeper in the cartilage. This is accompanied by evidence for increased formation of collagen fibrils and increased degradation and synthesis of aggrecan and type II collagen. The net contents of these proteoglycan per tissue do not, however, change until advanced degeneration occurs. These degradative processes are likely catalyzed by metalloproteinases and cysteine proteases. Cartilage exhibits significant capacity for remodelling which may be enhanced by therapeutic management of this process.

Cartilage, Articular↗

Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence for molecular heterogeneity and extensive molecular changes in disease.

Changes in the structure of the proteoglycan aggrecan (PG) of articular cartilage were determined immunochemically by RIA and gel chromatography and related to cartilage degeneration documented histologically by the Mankin grading system. Monoclonal antibodies to glycosaminoglycan epitopes were used. In all cartilages, three chondroitin sulfate (CS)-rich populations of large size were observed in addition to a smaller keratan sulfate (KS)-rich population. In grades 7-13 OA cartilages (phase II), molecules were significantly larger than the equivalent molecules of grades 2-6 (phase I). CS chain lengths remained unchanged. In most OA cartilages, a CS epitope 846 was elevated in content, this being most marked in phase II (mean: fivefold). Loss of uronic acid, KS, and hyaluronic acid were only pronounced in phase II OA because of variations in normal contents. Aggregation of PG was unchanged (50-60%) or reduced in OA cartilages, but molecules bearing epitope 846 exhibited almost complete aggregation in normal cartilages. This study provides evidence for the capacity of OA cartilage to synthesize new aggrecan molecules to replace those damaged and lost by disease-related changes. It also defines two phases of PG change in OA: an early predominantly degenerate phase I followed by a net reparative phase II accompanied by net loss of these molecules.

Aggrecans↗

Enzymatic activity and distribution of phospholipase A2 in human cartilage.

Extracellular phospholipase A2 (PLA2) with proinflammatory activity has recently been discovered in synovial fluids in inflammatory arthritides. In the search for the sources of synovial fluid PLA2, human synovium and articular cartilage were found to contain large quantities of the enzyme. In rheumatoid arthritis (RA), PLA2 activity in synovium, superficial and deep layers of articular cartilage was 20 +/- 14 (SEM), 168 +/- 62 and 533 +/- 176 nmol/min/mg protein respectively. Corresponding values in osteoarthritis (OA) were 49 +/- 11, 569 +/- 109 and 1709 +/- 243 nmol/min/mg protein, all significantly higher (p less than .01) than in RA. Nasal septal cartilage contained much less PLA2, 19 +/- 5.6. PLA2 in human articular and nasal cartilage has sn-2 specificity, a neutral pH optimum and absolute calcium dependence. High PLA2 concentration in articular cartilage may imply that, at least in part, cartilage is the source of PLA2 in the joint space. Since RA cartilage and synovium have less PLA2 activity than the corresponding OA tissues, additional sources of PLA2 in RA synovial fluids are implicated.

Arthritis, Rheumatoid↗

Failure of internal fixation of displaced femoral neck fractures in rheumatoid patients.

We reviewed the records and radiographs from 10 hospitals to identify 50 patients with rheumatoid arthritis (RA) who had sustained 52 femoral neck fractures. Most patients were female (88%), elderly (mean age 66 years) and had had severe polyarticular disease for a mean duration of 16 years. Over half had taken systemic corticosteroids, nearly all were severely osteopenic but few had rheumatoid changes in the hip. Of the 20 fractures treated by internal fixation 12 had complications including nonunion (5), osteonecrosis (5), infection (1), and intertrochanteric fracture (1). Only one of the nine undisplaced fractures required reoperation, but seven of the 11 displaced fractures had revision surgery. Twenty fractures were treated by primary total hip arthroplasty with only one early complication. The other 12 fractures had been treated by hemiarthroplasty (9), hip excision (1) or non-operatively (2). Our results suggest that, in elderly rheumatoid patients, severely displaced femoral neck fractures should be treated by total hip replacement.

Adult↗

The role of phospholipase A2 in the physiopathology of osteoarthritis.

High activity of phospholipase A2 (PLA2) was found in 58 synovial fluids of patients with osteoarthritis (OA), with a range of 2.2-75.1 nmol/min/ml and mean +/- SEM of 22.0 +/- 1.4 nmol/min/ml. This PLA2 was a calcium dependent enzyme composed of 2 isoforms called A and B. Twelve of 25 patients with OA (48%) were found to have high circulating PLA2, but no correlation to the numbers or size of affected joints was found. High concentrations of PLA2 were detected in human articular cartilage ranging from 33 to 4257 nmol/min/mg protein. The deep layers of the cartilage contained on average 3-fold more PLA2 than the superficial layers. Also synovial cells cultures and chondrocyte cultures that derived from OA joints synthesized and released PLA2 extracellularly. Since PLA2 is proinflammatory, its role in the inflammation that complicates OA process is highly probable. Further studies of PLA2 impact on OA joints and clinical trials with PLA2 inhibitors in OA are warranted.

Cartilage, Articular↗

Growth and detection of human bone marrow B-lineage colonies.

A reproducible method for growing normal human bone marrow B-lineage colonies in agar is described. The clonogenic cells require a rich medium, Opti-MEM (GIBCO/BRL, Burlington, Ontario, Canada), and a source of T-cell-derived factors for growth. The conditions described appear to be limiting for the colony progenitor, suggesting assay clonality. Three novel methods that permit routine and rapid detection of these human B-cell colonies are also described. Colonies containing cells that secrete immunoglobulin are detected by plaquing and protein immunoblotting, while RNA transcripts can be detected by RNA colony blotting. The detection of more than one secreted immunoglobulin isotype or RNA species in a single colony can also be achieved. This B-cell colony assay and the associated detection methods will allow the further delineation of human B lymphopoiesis in both normal and disease states.

B-Lymphocytes↗

Synthesis and release of phospholipase A2 by unstimulated human articular chondrocytes.

High activity of proinflammatory, type II phospholipase A2 (PLA2) was found in synovial fluids (SF) in inflammatory arthritis. In search for the sources of this PLA2, we cultured human articular chondrocytes and cartilage explants from healthy, osteoarthritic and rheumatoid joints. All cultures, unstimulated by cytokines, released PLA2 extracellularly. Cultures obtained from the deep layers of the cartilage released more PLA2 than those obtained from the superficial layers. Deep layer explants released 0.38 to 18.16 pmol/min/mg protein PLA2/day, whereas superficial layer explants released 0.39-3.18 pmol/min/mg/day. Chondrocyte cell cultures continuously released PLA2, in the first day 909-46347 pmol/min/(10)6 cells and after 9-26 days of culture 166-2115 pmol/min/10(6) cells. PLA2 released from chondrocytes was calcium dependent and had optimum activity at pH 7.5. Cycloheximide markedly inhibited its release. Chondrocyte cultures also released muramidase (LZM) but there was no correlation between PLA2 and LZM release. It may be concluded that cytokine unstimulated human articular chondrocytes synthesize and release PLA2 extracellularly which is similar to that found in the SF. Thus, chondrocytes may possibly serve as one of the sources of intraarticular PLA2.

Arthritis, Rheumatoid↗

Changes in the metaphysis and diaphysis of the femur proximal to the knee in rabbits with experimentally induced inflammatory arthritis.

We quantified the cross-sectional cortical bone area and remodeling rates in the ipsilateral femoral diaphysis and metaphysis of rabbits with carrageenan-induced inflammatory monarthritis of the knee. Although osteogenesis rates were significantly elevated (approximately threefold in diaphyses and sixfold in metaphyses), the cross-sectional bone area of the diaphysis was significantly diminished. Fivefold and sixfold increases in bone resorption rates were calculated in diaphyses and metaphyses, respectively. Other morphologic changes observed were porosity and net resorption of the anterior cortex and net accretion on the posteromedial cortex ("drift" of bone). These findings may have clinical significance with regard to the mechanisms and consequences of bone changes in patients with rheumatoid arthritis.

Animals↗

Juxtaarticular bone loss in experimental inflammatory arthritis.

The osteopenia associated with experimental inflammatory arthritis was studied by a histomorphometric method that exphasized net changes in bone composition. Juxtaarticular trabecular bone volume and turnover were studied in the carrageenan injection model of inflammatory arthritis of the mature rabbit knee. Trabecular bone volume was studied by histomorphometry of the femoral condyles and confirmed by photodensitometry on standard macroradiographs. Osteogenesis was studied by imaging of calcein fluorochrome-labeled newly formed bone in undecalcified histological sections. A significant net loss of cancellous bone (approximately 20%) occurred over 49 days in both the medial and the lateral femoral condyle in the arthritis group compared with normal controls. Total osteogenesis was increased fourfold and it was calculated that an even greater increase in total bone resorption was responsible for the negative bone balance. There is evidence that the periarticular bone loss of human rheumatoid arthritis is also associated with increased bone turnover. Quantitative studies of the kinetics of bone remodeling in inflammatory arthritis will provide the basis for therapeutic attempts to prevent or reverse arthritis-induced bone loss. Fracture risk in inflammatory arthritis may be increased not only by osteopenia, but additionally by the presence of a large proportion of newly formed (and presumably less mineralized) bone.

Animals↗