This report reviews imaging methods used for diagnosis and monitoring of rheumatoid arthritis, with emphasis on the role of ultrasonography. Traditionally, conventional radiography has been useful in detecting and monitoring the extent of joint destruction in rheumatic disease. However, it is particularly difficult to detect pathological joint changes in the early stages. Magnetic resonance imaging is able to detect inflammation of the synovial membrane and erosions but is limited by cost and availability. Ultrasound has recently emerged as a useful and potentially reliable method for assessing the degree of joint inflammation and erosion in patients with early rheumatoid arthritis.
Rheumatoid arthritis (RA) is characterized by inflammation and proliferation of synovial tissue, leading to degradation of articular cartilage and bone with functional impairment as a result. It has recently become clear that early suppression of synovial inflammation is essential in preventing progressive joint destruction, although inflammation and destruction are in part uncoupled. New insights into the role of matrix metalloproteinases (MMPs), aggrecanase, granzyme B, receptor activator of nuclear factor κB (RANK)–receptor activator of nuclear factor κB ligand (RANKL) interaction, and other factors involved in joint destruction may lead to the development of novel therapies aimed at specific inhibition of cartilage and bone degradation.
OBJECTIVE:To investigate the production of proinflammatory cytokines and expression of cell adhesion molecules in the rheumatoid nodule.METHODS:Cytokine content (tumor necrosis factor alpha [TNFalpha], interleukin-1beta [IL-1beta], and IL-1 receptor antagonist [IL-1Ra]), at the messenger RNA (mRNA) and protein levels, and cell adhesion molecule expression were studied in 16 rheumatoid nodules and 6 synovial membranes.RESULTS:Macrophages in the rheumatoid nodules contained TNFalpha, IL-1beta, and IL-1Ra mRNA and protein, particularly in perivascular cells of the stroma and in the palisading layer. All cell adhesion molecules studied were expressed in both the rheumatoid nodules and synovial membranes, with increased expression of E-selectin in the rheumatoid nodule compared with the synovial membrane, and with the absence of vascular cell adhesion molecule 1 expression on cells of the palisading layer in the rheumatoid nodule.CONCLUSION:The presence of similar proinflammatory cytokines and cell adhesion molecules in the rheumatoid nodule and synovial membrane suggests that similar pathogenic processes result in the chronic inflammation and tissue destruction in these lesions.
OBJECTIVE To establish the presence of inflammation in and cytokine production by synovial membranes from patients with various stages of early osteoarthritis (OA), with knee pain, normal knee radiographs, and arthroscopic evidence of chondral damage. METHODS Synovial membrane samples were obtained from the knees of 63 patients at the time of arthroscopy for unexplained knee pain or at the time of joint replacement surgery. Evaluations of synovial membrane variables including thickness of lining layer, vascularity, and inflammatory cell infiltrate were by a blinded observer. In a subset of 20 patients, production of interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), and IL-1 receptor antagonist (IL-1ra) at the mRNA and protein levels was determined using in situ hybridization with biotin labeled ribo-probes and immunohistochemistry. RESULTS There was evidence of thickening of the lining layer, increased vascularity, and inflammatory cell infiltration in synovial membranes from patients with all grades of OA, with the most marked changes seen in synovial tissue from patients with advanced grades of OA. Similarly, production of IL-1 alpha, IL-1 beta, and TNF-alpha was present in synovial membranes from all patients with OA, irrespective of the degree of articular cartilage damage. There was a trend to decreased levels of IL-1ra in synovial membranes from patients with OA that did not attain statistical significance. Similarly, there was a decrease in the ratio of IL-1ra to IL-1 alpha and beta with increasing grades of OA. CONCLUSION Chronic inflammatory changes with production of proinflammatory cytokines are a feature of synovial membranes from patients with early OA, with the most severe changes seen in patients at the time of joint replacement surgery resembling those seen in rheumatoid arthritis. This low grade synovitis results in the production of cytokines that may contribute to the pathogenesis of OA.
Current research into cytokine production in tissue sections relies on the detection of cytokine proteins using a variety of immunohistochemical methods. The disadvantages of this technique are that precise localization to a particular cell is difficult and it is uncertain whether the cells detected by this method are the origin or target of the cytokine or rather have nonspecifically absorbed the secreted cytokine. This question can be clarified using in situ hybridization, but current techniques are insensitive, poorly localizing, or time consuming. Biotin-labeled riboprobes were generated from cDNA fragments sandwiched between two RNA polymerase promoters (SP6 and T7 RNA polymerases) using a commercial riboprobe generation kit containing biotin-labeled UTP. The in situ hybridization technique was used to demonstrate cytokine mRNA in a range of tissues containing an inflammatory infiltrate and with a range of cytokine probes. This technique of in situ hybridization was combined with immunohistochemistry using an immunoalkaline phosphatase technique to show the powerful combination of these two techniques. The biotin-labeled riboprobes were sensitive enough to detect a range of cytokine mRNAs in a variety of tissue sections. The technique can be completed over a 24-h period and produces a stable color product that can be stored for long periods and can be quantitated using image analysis techniques. This technique was performed on paraffin-embedded tissue as well as cryosections and allowed for the detection of mRNA in archival tissue. It was also successfully combined with immunohistochemical techniques to determine simultaneously the localization of a cytokine product in particular cell lineages. A nonradioactive method for in situ hybridization using biotin-labeled riboprobes is described; it is capable of detecting mRNA products from a range of genes in a variety of tissue samples. An amplification step in the method enhances the sensitivity to a level that approaches that of radioactive methods, while maintaining the speed, safety, and simplicity of an immunoperoxidase detection system. The ability to use paraffin-embedded tissue with this method allows for improved tissue architecture and examination of archival tissue. These features should ensure greater use of in situ hybridization techniques in future research studies.
An overview of the development of document supply relationships between libraries and publishers reveals four major areas leading to fee based (copyright) document delivery.
BACKGROUND:Scleroderma is a systemic rheumatic disorder seen in a wide range of clinical specialties.AIMS:To establish the prevalence and mortality rates of scleroderma in South Australia (SA), to determine the relative frequency and characteristics of the three principal subsets (diffuse, limited and overlap), and to examine the role of nailfold capillaroscopy in subset identification and implied prognosis.METHODS:Outpatient and discharge diagnostic indexes from five major teaching hospitals in SA were reviewed between February 1987 and November 1993. A total of 215 patients with scleroderma were identified. Case notes of 115 of these patients were reviewed in order to validate scleroderma diagnosis, and subset characteristics such as sex, mean age at diagnosis, extent of skin involvement, internal organ involvement and serology were analysed. Fifty-two of these patients were then examined prospectively to confirm positive discharge diagnosis, and nailfold capillaroscopy was performed on these patients.RESULTS:The point prevalence of scleroderma in SA for 1993 was estimated to be 208/10 This figure is a conservative estimate and is higher than most other reported series. The female to male ratio was 4:1. The majority of patients had limited disease with a ratio of 6:1:1.6 limited vs diffuse vs overlap. Systemic involvement excluding the oesophageal components limited disease was found predominantly in the diffuse group. Autoimmune serology was positive in 90% of patients, with Scl-70 being more common in diffuse scleroderma, anti-centromere antibody (ACA) in the limited form and anti-ribonucleoprotein (RNP) in the overlap form. Nailfold capillaroscopy was useful in predicting disease-subtype as capillary dilatation was observed predominantly in limited disease, capillary dropout in diffuse disease.CONCLUSIONS:Scleroderma is more common in SA than previously recognised. Limited disease is more common than diffuse or overlap disease, carries a better prognosis and in associated with ACA. Nailfold capillaroscopy is a useful tool in disease assessment and may provide useful diagnostic and prognostic information.
We report the complication of cardiac tamponade occurring secondary to a pericardial effusion in a patient with persistently seronegative rheumatoid arthritis. The frequency and presenting features of this potentially life threatening complication of rheumatoid arthritis are reviewed and management of this complication is discussed.
This article summarizes the findings of a study aimed at focusing attention on the whole range of costs associated with interlibrary lending. Comparative costs of the ways in which interlibrary loans may be obtained are presented. The results distinguish between the costs incurred by a particular library in a transaction, and the net effect of the transaction on the finances of all libraries involved. Three universities, one polytechnic, two public and one industrial library, a regional library bureau and the British Library Lending Division took part in the study. The simplest successful interlibrary loan transaction, involving the supply of an average length photocopy, costs around £2.00 and the minimum cost of a loan is in the region of £4.00, both at 1981 prices. The investigation illustrates that generally the over‐all cost to the library community of a transaction which results in the supply of an item from Lending Division stock, is likely to be less than that of an application involving a regional library bureau or one sent direct to another library. The use of the Lending Division loan/photocopy form for interlending is shown to provide an equitable means of sharing the costs of interlibrary loans.
An 83 year old female presenting with a symmetrical peripheral polyarthritis resembling rheumatoid arthritis, subsequently developed biopsy-proven temporal arteritis. This case report draws attention to this uncommon presentation of temporal arteritis and briefly reviews common presenting features of this condition.