A biography of the chondrocyte.

Significant gaps persist in our understanding of chondrocyte biology. We do not know when, how, or even whether these cells are replenished throughout the normal, human life span. We are taught that as much as 90% of the cartilage is "metabolically inert" interterritorial matrix, but we do not know how this substance is regularly replaced (as it is known to be) by the distant chondrocytes, We recognise that the "tidemark" is the most conspicuous histological feature within cartilage, but we do not understand why that layer stains with haematoxylin or what that may imply for the biology of the tissue. These, and other issues may be clarified if the lifetime of each chondrocyte begins as a mesenchymal stem cell at the articular margin, plays out over years on an arcing trajectory along collagenous guidelines, and ends as an extracellular deposit of intracellular remains at the interface between uncalcified and calcified cartilage. This hypothesis is presented here, and some of its potential implications are considered.

Effect of tumour necrosis factor alpha antagonists on serum transaminases and viraemia in patients with rheumatoid arthritis and chronic hepatitis C infection.

BACKGROUND: Tumour necrosis factor alpha (TNF alpha) antagonists are effective for the treatment of rheumatoid arthritis (RA), but concerns remain about the safety of these agents in the presence of chronic infections, including hepatitis C virus (HCV) infection. OBJECTIVE: To examine the influence of treatment with TNF alpha antagonists on levels of HCV viraemia and serum transaminases in patients with RA and HCV. METHODS: In a retrospective survey the course of 16 HCV infected patients with RA who had received the TNF alpha antagonists etanercept or infliximab was analysed. Eight additional patients with RA and HCV were also enrolled into a three month prospective trial of etanercept. Serum concentrations of albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and HCV were followed. RESULTS: Viraemia was measured in 22 patients receiving a TNF alpha antagonist at the start of treatment and after 1-34 months (median 9 months follow up). Twenty four patients had serial tests of liver related enzymes and albumin. None of the differences between liver related tests at baseline and at follow up achieved significance (p>0.05). Similarly, the mean HCV measurement at 1-3, 4-6, 7-12, and 13-34 months did not differ significantly from baseline (p>0.05). CONCLUSION: In this study, liver related blood tests and HCV viral load measurements did not change substantially. These findings suggest that TNF alpha antagonists merit further study for the treatment of RA in HCV infected patients. Larger and longer term studies are still needed.

Acetabular osteitis in ankylosing spondylitis: does fibrillin figure in its pathogenesis?

In the hip and sacroiliac joints, ankylosing spondylitis attacks the acetabulum over the femoral head and the ilium in preference to the sacrum. Both sites involve inflammation in bone subjacent to fibrocartilage with relative sparing of opposing, hyaline cartilage-surfaced mates. This disease appears to target connective tissues rich in fibrillin-1. A cell-mediated autoimmune response may be involved.

Continuous passive motion for osteoarthritis of the hip: a pilot study.

OBJECTIVE: To evaluate whether extended use of continuous passive motion (CPM) may allay the pain of walking, diminish disease effect, and increase the usual walking speed in patients with osteoarthritis (OA) of the hip. METHODS: This pilot study comprised 21 patients with Kellgren-Lawrence grade 2-4 OA of the hip who used CPM for periods of 1.2 to 7.6 h daily throughout a 12 week trial. RESULTS: Significant improvements were found in the patients' assessment of pain on visual analog scale, Sickness Impact Profile, self-selected walking speed, and the number of subjects who decreased their medication usage. None of these improvements was related to the radiographic grade of the patients' OA or the daily duration of CPM. CONCLUSION: Although regular exercise is now routinely recommended to patients with OA, there has been relatively little study of specific exercise programs. As such investigations are undertaken, we believe CPM should be included among the options that are studied.

Gout and hyperuricemia.

Although there continue to be relatively few basic studies of the metabolism and transport of urate, clinical interest in gout and hyperuricemia remains high. A number of interesting new observations are described here from the published literature of the past year. Various aspects of the diagnosis, management, and pathophysiology of gout and gouty arthritis have been recently reviewed. The therapy of gout and hyperuricemia continue to lead to significant complications.

Subchondral plate thickness reflects tensile stress in the primate acetabulum.

To evaluate possible relationships between body size and articular architecture, femoral head radius and subchondral plate thickness were assessed in skeletal hip joints from normal primates. The relative "contact pressure" on bearing surfaces was estimated from the measured radius and the normal body mass in species ranging from Cebuella pygmaea (0.1 kg) to Gorilla gorilla (170 kg). Subchondral plate thickness was evaluated by computed tomography in species ranging from Cercopithecus neglectus (4.0 kg) to Gorilla gorilla. Neither the "contact pressure" nor the thickness of the femoral subchondral plate varied substantially among species. In contrast, the acetabular subchondral plate thickened significantly (p = 0.01) as body size increased. This finding is interpreted as an osseous response to tensile acetabular stress, which can be expected to increase directly with the radius of curvature.

Quantitative magnetic resonance imaging predicts clinical outcome of core decompression for osteonecrosis of the femoral head.

OBJECTIVE: To determine whether the course of femoral head osteonecrosis after core decompression can be predicted from the extent of necrotic bone in the preoperative magnetic resonance imaging (MRI). METHODS: In 31 femoral head lesions (Ficat stage I or II), the percentage volume of necrotic bone was calculated by dividing the sum of the necrotic areas from all MRI slices by the sum of the femoral head areas. Osteonecrosis risk factors, pain scores, and the need for further surgery were assessed at a minimum of 12 mo post-core decompression. Clinical outcomes were considered good when post-core decompression pain scores improved and further surgery was not required. RESULTS: Fourteen of the 15 hips with good outcomes after a mean followup of 32 mo had less than 21% femoral head involvement. All 16 hips with poor outcomes after a mean followup of 17 mo had more than 21% of the femoral head affected. CONCLUSION: Quantitative MRI of femoral head necrosis was a useful predictor of clinical outcome following core decompression.

Synovial perfusion in the human knee: a methodologic analysis.

Synovial perfusion was quantified in milliliters per minute per knee by two quite different clearance methods based on (1) counting tritiated water in serial aspirates of intraarticular saline, and (2) external counting of joints injected with free radioiodide. In each case, the serial counting data determine a rate constant that is multiplied by a distribution volume to provide the clearance in flow terms of milliliters per minute. This report updates and summarizes these data and compares the two methods to each other and to alternative assessments of synovial blood flow. Available methods such as laser Doppler flowmetry (with data output measured in volts) and solute clearance constant determinations (in min-1) are useful for selected purposes but cannot be used to quantify the articular flux (in milligrams per minute) of any solute. Radiolabeled microspheres provide data (in milliliters per minute per g of tissue) but are unsuitable for human use. The two clearance methods provide comparable results, but the free iodide technique seems most suitable for physiologic investigations. The latter potentially includes critical evaluations of synovial blood flow in relation to issues such as palpable warmth, visible erythema, articular ischemia, the permeability of synovial vessels, the genesis of effusions, the delivery and removal of therapeutic agents, and the concentration of every synovial fluid solute from micronutrients through cytokines, plasma proteins, and molecular markers of cartilagenous injury.

Cartilage matrix molecules in serum and synovial fluid.

The search continues for constituents of articular cartilage in the serum and synovial fluid of patients with arthritis. This work is driven by the hope that such "markers" will be useful in the diagnosis and management of rheumatic diseases. Absent information about the kinetics of these molecules continues to hinder interpretation of their concentration. Recent progress includes recognition of markers that appear to be specific for diseased cartilage and identification of factors that may distinguish between reversible and irreversible disease.