W. Watson Buchanan

The use of NSAIDs in rheumatic disorders 2005: a global perspective.

Population studies and World Health Organisation (WHO) statistics indicate that 10–50% of individuals suffer from musculoskeletal disorders. Up to 3% will be classified as disabled due to their bone and joint condition, and the majority will suffer from pain. Almost all will require non-steroidal anti-inflammatory drugs (NSAIDs) and other analgesics for their management. The large majority of this population is elderly and, hence, at greater risk of adverse effects to the NSAIDs. The NSAIDs are a necessary choice in pain management because of the integrated role of the cyclo-oxygenase (COX) pathway in the generation of inflammation and in the biochemical recognition of pain. For over 80 years the management of musculoskeletal pain was hampered by NSAID toxicity problems related to the traditional NSAIDs. In the early 1990s, paracetamol was recommended as the first-choice analgesic for osteoarthritis, but subsequent studies have shown that paracetamol has a significant gastrointestinal (GI) toxicity profile. In addition, it has lower analgesic efficacy than NSAIDs and is, thus, not an effective alternative to NSAIDs in any of the inflammatory arthritides. The identification of cyclo-oxygenase 2 (COX-2) and the subsequent introduction of the COX-2-selective inhibitor NSAID drugs was thought to be a major breakthrough with the expectation of a significant reduction in G/I side-effects. This has not been the case for celecoxib, and indeed for all COX-2-selective inhibitors when given with ASA. The COX-2-selective inhibitors also inhibit renal COX-2 with the potential for problems of fluid retention, oedema, hypertension and congestive heart failure. The major controversy with respect to the COX-2-selective inhibitors as a class has been the increase in myocardial infarction and other cardiovascular events observed in some studies. Thus, the initial expected global benefits of the COX-2-selective inhibitors may be outweighed by their potential for toxicity. Recent studies have shown that the use of a proton-pump inhibitor drug with traditional NSAIDs and with COX-2-selective inhibitors has been shown to significantly reduce GI symptoms and peptic ulceration. Thus, the traditional NSAIDs have been re-established as the preferred choice in the management of arthritis and musculoskeletal disorders.

Osteoarthritis: symptoms, signs and source of pain

Osteoarthritis is the most common form of arthritis. The condition is characterised by loss or failure of the functional and/or biochemical integrity of the joint. The clinical symptoms include joint stiffness, pain and dysfunction, but the principal problem for the majority of patients is the pain. Although there are no pain receptors in the cartilage, the origin of the pain is thought to be due to stimulation of the A delta mechanoreceptors and the C polymodal nerve endings in the synovium and surrounding tissues. However, some of the pain experienced in and around the joints is referred pain or sympathetic efferent pain. In addition, there is a poor correlation of clinical symptoms with radiological or imaging appearance. This lack of correlation of clinical evaluation and imaging makes attempts at treatment difficult and compromises attempts to design studies and to evaluate the outcome of osteoarthritis in clinical trials.

Circadian rhythm in pain, stiffness, and manual dexterity in rheumatoid arthritis: relation between discomfort and disability.

Fourteen patients with rheumatoid arthritis (RA) self rated their pain and stiffness on separate 10 cm visual analogue scales and performed bead intubation coordinometry (BIC) on six occasions each day for seven consecutive days. In addition, 14 healthy controls matched for age and sex also performed BIC measurements according to the same schedule. Data were analysed using least squares and cosine vector techniques. Significant circadian rhythms in patients with RA were detected in pain, stiffness, and BIC, and in controls in BIC. Pain was least in patients with RA at 1700 and stiffness at 1724. Peak BIC performance occurred almost simultaneously in RA (1544) and control (1528) subjects and for subjects with RA occurred within the 95% confidence interval of least pain and stiffness. These data suggest that the inferior performance of subjects with RA may be an accentuation of the normal physiological variation seen in healthy controls, but may be modulated by the patients level of pain or stiffness, or both.

Rhythmic variations in pain, stiffness, and manual dexterity in hand osteoarthritis

Objective: To explore circadian variation in pain, stiffness, and manual dexterity in patients with hand osteoarthritis (OA). Methods: Twenty one patients with hand OA, as defined by ACR criteria (17 women, four men, mean age 62.2 years, range 52–74 years) self rated pain and stiffness on separate 10 cm horizontal visual analogue scales and performed bead intubation coordinometry (BIC) six times each day (on waking up, at bedtime, and every four hours in between) for 10 consecutive days. Each series (using data with the trend removed if there was a significant trend) was analysed for circadian rhythmicity by a cosine vector technique (single cosinor). With individual data expressed as the percentage of the mean, group rhythm characteristics at period 24 hours were summarised for each variable by population mean cosinor analysis. Results: Individual analyses identified significant circadian rhythms at p≤0.05 for pain (n=15/21), stiffness (n=16/20), and dexterity (n=18/21), and a significant circadian rhythm on a group basis was identified for pain (p=0.013), stiffness (p<0.001), and dexterity (p<0.001). Pain was least at 1610 and stiffness at 1618. Peak dexterity occurred in mid-afternoon at 1548 and occurred within the 95% confidence interval of least pain (1312–1800) and stiffness (1520–1732). Conclusions: Dexterity was influenced by the patients level of pain or stiffness, which changed systematically throughout the day. Similar results have been previously reported in 14 patients with rheumatoid arthritis where peak dexterity occurred at 1544 and at 1528 in 14 age and sex matched healthy controls. The predictability of rhythmic variation in pain, stiffness, and dexterity has implications for scheduling activities of daily living and for timing antirheumatic drug treatment.

Pathogenic responses of bradykinin system in chronic inflammatory rheumatoid disease

Excessive release of kinin (BK) in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 kinin receptors. Activation of the kinin forming system could be mediated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokine and cytokine mediators of inflammation, e.g., PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF, derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessel proliferation, inflammatory cell migration and, possibly, angiogenesis in pannus formation. These pathological changes, however, are not yet defined in the human model of chronic inflammation. The role of kinins and their interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes, such as rheumatoid arthritis, periodontitis, inflammatory diseases of the gut and osteomyelitis. Future development of specific potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as a pharmacological basis for more effective treatment of joint inflammatory and related diseases.

Gold induced thrombocytopenia: 12 cases and a review of the literature

Gold induced thrombocytopenia is immune mediated, with the production of platelet associated IgG leading to peripheral platelet destruction. An association with HLA-DR3 has been demonstrated. Corticosteroid therapy is effective in treatment, although other modes of therapy may be as efficacious.

Ultrasonography after hip arthroplasty

Ultrasonography was performed in 55 patients who had total Charnley hip arthroplasties. Effusions were identified in 19 patients and confirmed in all but 3 by arthrocentesis or at surgery. Aspirations were performed in 5 and demonstrated infection in 2. It is concluded that ultrasound is a valuable noninvasive method for assessing painful hip arthroplasty. It can demonstrate the presence of effusion, which should be aspirated to exclude infection.

Controlled, double-blind, randomized trial of amitriptyline in relieving articular pain and tenderness in patients with rheumatoid arthritis

Thirty-six patients with definite or classical rheumatoid arthritis participated in a double-blind, randomized, placebo-controlled trial to assess the effectiveness of adding amitriptyline to the treatment regimen for the relief of pain not adequately controlled by non-steroidal anti-inflammatory drugs. Dosage of amitriptyline was increased gradually up to 25 mg 3-times daily and patients were followed up for 12 weeks. Assessments were made of joint pain and tenderness every 4 weeks. The results showed no difference between the amitriptyline and placebo-treated patients for either parameter.

Osteoarthritis IV: Clinical therapeutic trials and treatment

This article discusses the potential usefulness of clinical therapeutic trials and criticises the failure of the value of guidelines in the management of osteoarthritis (OA). We have provided an overview of the benefits and side effects of non steroidal anti-inflammatory drugs (NSAIDs) in OA, including the introduction of the COX-2 selective inhibitors. In addition we have briefly reviewed the use of local NSAIDs, narcotic analgesics, injection methods, disease modifying drugs, gene therapy, surgical treatment, and non pharmacological intervention.

Zinc: Its Relationship to Osteoporosis in Rheumatoid Arthritis

Preliminary studies indicate that plasma zinc concentrations, as estimated by atomic absorption spectrophotometry, are reduced in rheumatoid arthritis. A relationship has also been established between metacarpal index of osteoporosis and plasma zinc concentrations in rheumatoid subjects.