Chronic Polyarthritis Research Articles

Increased CSF protein in chloroquine-induced axonal polyneuropathy and myopathy

Objectives: Few data are available about myopathy and polyneuropathy as rare side effects of chloroquine treatment. Even more rarely are cerebrospinal fluid (CSF) abnormalities in chloroquine polyneuropathy/myopathy. Case description: The patient is an 81-year-old woman with a 30-year history of chronic polyarthritis. As a basic therapy, she received chloroquine (250 mg per day) since 1997. Already, 1 year later she developed slowly progressive gait disturbance, which led to recurrent falls, and forced her to use crutches and other orthotic devices. Since March 2001, she was no longer able to climb stairs. Since then she also developed sensory disturbances in both lower limbs. Clinical neurological investigation revealed weakness and wasting of all four limbs and reduced tendon reflexes and stocking-type sensory disturbances. Nerve conduction studies were indicative of an axonal polyneuropathy. Electromyography was non-specifically abnormal. Muscle biopsy of the gastrocnemius muscle disclosed neuropathic and myopathic features and frequent fibers with partially rimmed vacuoles, containing concentrically or parallelly sliced inclusions. CSF investigations disclosed increased protein but otherwise normal findings. Five months after discontinuation of chloroquine and replacement by leflunomid, there was marked clinical improvement. Conclusions: Chloroquine polyneuropathy/myopathy may go along with increased CSF protein. Discontinuation of the causative agent results in prompt recovery of the described abnormalities.

Mouse Arthritis Model Induced by Anti-Type II Collagen Monoclonal Antibody Cocktail: Difference in Distribution of Diseased Joints by Strain and Immunodeficient Status

Murine collagen-induced arthritis (CIA) is widely used as an experimental model for human rheumatoid arthritis (RA) . The antibodies specific for type II collagen have an important role in the onset of RA. In technical cooperation with Chondrex Inc. (Seattle, U.S.A), we have developed the novel reagent kit to induce murine arthritis with high efficiency. The kit, referred to Arthritogenic mAb Cocktail (Immuno-Biological Laboratories, Chondrex), is comprised of four kinds of mouse monoclonal antibody (mAb) and LPS. Each of antibodies recognizes different epitopes on type II collagen.The arthritis in multiple joints of limbs was successfully induced within 4 days after treatment of mouse with intravenous injection of 2 mg of mAb mixture and intraperitoneal injection of 50μg of LPS three days after the mixture injection in BALB/c and DBA/1 strain, while iv injection of 5 mg of mAb mixture followed by ip injection of 50μg of LPS was required for induction of arthritis in C57BL/6 strain.Severity of arthritis in BALB/c mice was augmented according to increase in amount of mAb mixture injected. The disease lasted for about three weeks and it could become more chronic by additional administration of either the antibody cocktail or LPS.In BALB/c strain, the arthritis was developed on four limbs with equal grade, whereas in DBA/1 and C57BL/6 strains the forefeet were affected more prominent than the hindfeet.BALB/c-Nude and C.B-17/Icr SCID mice were also subjected to the induction experiment and the arthritis was brought on SCID but not on nude mice.These results show that antibody production for type II collagen in vivo is bypassed with use of the kit and the arthritis can be induced easily and constantly on various kinds of mouse strain without restriction of MHC class. Thus, these stable mouse models for acute and chronic polyarthritis could be useful for screening and/or invention of anti-inflammatory as well as anti-arthritic remedies.

Clinical Findings Associated with Borrelia burgdorferi Infection in the Dog

Borrelia burgdorferi, the aetiological agent of Lyme disease, is transmitted to humans and animals by Ixodes ticks during the blood meal. In dogs the micro-organism is known to induce a variety of clinical symptoms, particularly acute and chronic skin lesions, polyarthritis, pericarditis and inflammation of the central and peripheral nervous systems. The diagnosis of borreliosis is made on the basis of a history of tick exposure, symptomatology, micro-biological and serological examinations and treatment response (Straubinger, 2000). The course of the disease may be asymptomatic, although the serological tests are often positive, with high antibody titres possibly indicating a previous disease or premunition (Burrascano, 2000). In this paper we report the course, the clinical features and the therapeutic protocol in a Pitbull seropositive for B. burgdorferi.

Short-wave diathermy: current clinical and safety practices.

Short-wave diathermy (SWD) is widely available, yet a comprehensive examination of current clinical practice remains absent from the literature. The present paper aims to assess clinical and safety issues in continuous (CSWD) and pulsed (PSWD) short-wave diathermy application and subsequently indicate areas for future research. A postal survey was carried out among 116 senior physiotherapists in 41 Irish hospital-based physiotherapy departments. The response rate to the study was 75%. Analysis found that PSWD was the preferred mode of treatment with 27% of respondents using it more than once daily. Respondents considered both modes of treatment indicated for a variety of conditions. CSWD was rated as an effective treatment for chronic osteoarthritis, polyarthritis, non-specific arthrosis and haematomas. PSWD was reported an effective modality for acute soft tissue injury, haematomas, acute osteoarthritis, sinusitis and rheumatoid arthritis. Dose selection varied greatly but tended to be based on the type, nature and duration of the condition. Analysis of safety practices uncovered concerning findings. Although a high level of agreement was found on measures for patient safety, 30% of respondents reported that no measures for operator safety were taken and only five respondents stated they remained a specified distance from SWD equipment. Measures to ensure the safety of other personnel in the physiotherapy department were also lacking. Given the availability of SWD equipment and its apparent efficacy in certain conditions, future research should aim to establish this by means of controlled clinical trials. The findings on safety practices underline the urgent need for comprehensive guidelines to ensure the safety of operators, patients and the general public during SWD application.

Relationship of Polyarthritis and Respiratory Disease in Cattle

Nearly 15 years' experience with a chronic pneumonia and polyarthritis syndrome (CPPS) in western Canadian feedlots is described. Emphasis in this presentation is on the postmortem and laboratory diagnosis of CPPS. Mycoplasma bovis is the most consistent etiologic agent isolated, but in the author's experience and opinion, chronic primary BVDV infection likely plays a significant role in predisposing to this antibiotic-unresponsive infectious disease problem. The syndrome appears to be a problem throughout North America and is an increasing problem in some dairy herds as well. The Haemophilus somnus disease complex (HSDC) is a less-common cause of concurrent respiratory and joint infections and is much simpler to diagnose.

Kunsttherapie: Entwicklung und Evaluierung eines Beobachtungsinstruments zur systematischen Analyse von Patientenbildern aus der Onkologie und der Rheumatologie

Art Therapy: Development and Evaluation of an Instrument to Analyze Paintings of Patients in Oncology and Rheumatology Systematically Introduction: Art therapies have been established methods in oncology for many years. To what extent patients’ pictures can be systematically described, and what connections to various illnesses are possibly thereby revealed, has been discussed in various specialized medical fields for over a hundred years. The following paper first presents insight into the present stand of research and then presents the results of the study. Question: Are systematic analyses of pictures possible with the use of the instrument we have developed? Are pictorial differences evident within the researched group? Method: A previously developed instrument was submitted for expert questioning for the purpose of the study. The instrument that had been modified on the basis of these results could then be used in the study to interpret 162 pictures. Four different raters, three of whom were acquainted with neither the patients nor the pictures, interpreted these pictures independently of one another. Results: The evaluation of the expert interpretations shows that this newly developed instrument is suitable for the differentiated description of patients‘ pictures. First important indications were drawn in regard to the pictorial differences between the two examined groups of cancer patients and patients with chronic polyarthritis. Conclusion: Systematic picture analyses are possible. A further analysis of the expert interpretations is necessary to clarify questions raised by the pictorial differences found in the various diagnostic groups.

Immunization of Rats with Homologous Type XI Collagen Leads to Chronic and Relapsing Arthritis with Different Genetics and Joint Pathology Than Arthritis Induced with Homologous Type II Collagen

The most commonly used animal model for rheumatoid arthritis (RA) is collagen-induced arthritis (CIA), induced by immunization with type II collagen (CII), a cartilage restricted protein. In this work we show that type XI collagen (CXI), which is a minor component in cartilage, induces a different form of erosive and chronic relapsing polyarthritis in rats. Using a series of inbred rat strains involving various genetic backgrounds (DA, LEW, E3), and congenic MHC regions (a, u, f, n, c, d), we found that CXI induced arthritis (CXIIA) is associated with the RT1f haplotype in contrast to CII induced arthritis (CIIIA), which is associated with the RT1a and RT1u haplotypes. The CXIIA follows a chronic disease course affecting peripheral joints with both progression and relapses, which appear not to cease (occurring >800 days). Susceptible strains showed a sustained antibody response to CXI with time indicating that the autoimmune response was self-perpetuated. Microscopic analysis of the joints at different stages demonstrated the severe destruction of bone and cartilage by pannus tissue consisting of activated macrophages and T cells. The main difference to joints from rats with CIIIA was larger numbers of infiltrating lymphocytes and these tended to form follicle-like aggregates. Surprisingly, males were more susceptible to CXIIA than females whereas the opposite has been observed in other rat arthritis models, including CIIIA. Taken together, CXIIA is a chronic relapsing and erosive polyarthritis that is MHC associated, which in fact fulfills the criteria for diagnosis of RA. Thus the CXIIA model will be useful as a novel and relevant animal model for RA.

Early diagnosis of chronic polyarthritis with conventional roentgen imaging

Radiographs used to be the gold standard of imaging techniques in rheumatoid arthritis. New imaging techniques allow more detailed examinations of soft tissue changes, the predominant features of early RA. This could change the place of radiography especially in this phase of the disease. The best available radiographic technique is necessary to capture the changes of early RA. Radiographs of both hands and feet are needed for early diagnosis and standardized follow-up. Extent and distribution of indirect signs of arthritis (soft tissue swelling and juxtaarticular osteoporosis) vary with disease activity but can provide important information also for the differential diagnoses. Inter-reader reliability of these changes is low, thus, questioning the validity of these findings. Direct signs of arthritis (erosions and joint space narrowing) are more easy to detect and are used for the quantification of the long-term disease course, in clinical studies, as proof for the disease modifying property of an intervention. Direct signs of arthritis are also found in other diseases, so they are not exclusive signs of RA. Nevertheless a typical radiographic finding in early RA is highly specific and is the most important risk factor for a poor prognosis. Therefore, it serves as the basis for therapeutic decisions, e.g., for an early aggressive treatment. As long as there are no data that the findings with the new imaging techniques are as relevant for prognosis, radiographs cannot be replaced in early RA.

Magnetic resonance imaging in the assessment of synovial inflammation of the hindfoot in patients with rheumatoid arthritis and other polyarthritis

Objectives: To describe the localisation of synovitis and tenosynovitis of the hindfoot observed on magnetic resonance imaging (MRI) in patients with chronic polyarthritis, and to correlate the findings of physical examination and MRI. Methods: Patients with chronic polyarthritis, and one or two painful hindfoot were included. On physical examination and on MRI, the tibio-talar, talo-calcaneal, and talo-navicular and calcaneo-cuboidal joints were adjudged to have or not synovitis, and the tibialis anterior and posterior, the peroneus longus and brevis, the flector digitorum and hallucis longus tendons to have or not tenosynovitis. Criteria for synovitis and tenosynovitis were a high signal intensity on T2-weighted images, a low signal intensity on T1-weighted images, and enhancement after Gd-DTPA injection, in the joint area, and around the tendon, respectively. The correlation between the findings of physical examination and those of MRI were evaluated using the Kappa statistics. Results: 12 patients (three men, nine women, mean age of 55.5 years±11.4 S.D.) with chronic polyarthritis (rheumatoid arthritis (RA): nine, ankylosing spondylitis: one; psoriatic arthritis: one, unclassified: one) were included. All presented with one (7 patients) or two (5 patients) painful hindfeet (and swelling for 16 out of 17 hindfeet). On physical examination, 25 joints and eight tendons were adjudged to have synovitis and tenosynovitis. MRI showed synovitis in 12 out of 25 of these joints (48%), and tenosynovotis in three out of eight of these tendons (37.5%). Moreover, MRI showed ten and seven clinically unsuspected synovitis and tenosynovitis, respectively. The proportion of agreements between physical examination and MRI were 54.9% (kappa=0.1) and 88.2% (kappa=0.27) for synovitis and tenosynovitis, respectively. Conclusion: A weak correlation was observed between the findings of physical examination and MRI in patients with chronic polyarthritis and a painful hindfoot. MRI might be used to localise synovitis in the area before performing some intra-articular injections. However, other studies are needed to address this question.

Health economics research in the area of chronic polyarthritis

Costs of illness are of major economic relevance in rheumatoid arthritis (RA) as in other chronic diseases. Overall costs of 15,000 Euro/year: 10,000 Euro indirect costs, and 5000 Euro direct costs are estimated, respectively. A further detailed analysis of direct costs underlines that inpatient care (50%) is the most prominent cost driver. Medication costs are also evaluated in detail since they are expected to gain importance with the introduction of the more expensive biologicals. While annual costs for regular disease modifying drugs (DMARDs) vary from 160 to 5000 Euro per patient, costs for the new biologicals amount up to 20,000 Euro (100-125% of the current estimated overall costs). For a comparison of different therapeutic strategies, costs are related to effectiveness in cost-effectiveness analyses. Based on present clinical trials, the ratios of medication costs and response according to the ACR 20-criteria of various DMARDs and biologicals are compared. The most cost-effective medication is sulfasalzine, followed by methotrexate, and leflunomide. Combining etanercept and methotrexate is preferable to methotrexate monotherapy and the combination of infliximab and methotrexate. This review shows that important economic issues in RA have already been addressed by applying cost-of-illness analyses and cost-effectiveness analyses. However, the knowledge about cost-effective therapeutic options is still scarce. Thus, primary data will have to be obtained using standardized approaches. These economic findings can be taken into account in the development of disease-management recommendations for RA-therapy.

Chemically modified ribozyme targeting TNF-alpha mRNA regulates TNF-alpha and IL-6 synthesis in synovial fibroblasts of patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is chronic polyarthritis in which a variety of inflammatory cytokines play a role. Since tumor necrosis factor-alpha (TNF-alpha) is one of the most important cytokines in the pathogenesis of RA, we evaluated the feasibility of ribozymes as a therapeutic agent to control the inflammatory process of RA synovium. A hammerhead ribozyme against TNF-alpha was chemically modified to increase nuclease resistance and added to RA fibroblastlike cell cultures without using a delivery system. The cellular uptake of fluorescent-labeled ribozyme into synovial cells was found to last at least 48 hr by confocal laser scanning microscopy. The ribozyme targeting TNF-alpha gene inhibited both the expression of TNF-alpha mRNA and the secretion of TNF-alpha and IL-6. The cytotoxic effect by the ribozyme on synovial cells was negligible when determined by an alamar blue assay. Chemically modified ribozymes designed to suppress the TNF-alpha gene may be potential as a therapeutic agent for rheumatoid arthritis.

Exocrine Dysfunction of the Pancreas in Patients with Chronic Polyarthritis

We studied the extent to which exocrine dysfunction of the pancreas is seen among patients with severe chronic polyarthritis and whether it might account for some gastrointestinal symptoms. Our series consisted of 50 such chronic polyarthritis cases; most had rheumatoid arthritis but had neither diagnosed or suspected pancreatitis nor primary Sjögren's syndrome. They were asked about gastrointestinal (GI) and sicca symptoms. The exocrine function of each pancreas was evaluated by the fecal elastase-1-enzyme test. Thirty-two patients had GI symptoms at least weekly. Forty had sicca eye syndrome and 26 had dry mouth. There were two cases (4%; 95% confidence interval, 1-14%) with abnormally low fecal elastase-1-enzyme test level. Chronic GI and sicca symptoms are frequent among patients with severe chronic polyarthritis. Secondary Sjögren's syndrome may cause exocrine insufficiency in the pancreas. That circumstance was not common here, but it is worth remembering because it can be diagnosed by a noninvasive method, and enzyme preparation treatment is available for the symptoms, especially for postprandial pain and distention of the stomach.

Chronic relapsing homologous collagen-induced arthritis in DBA/1 mice as a model for testing disease-modifying and remission-inducing therapies.

To test whether the chronic relapsing arthritis induced by immunizing DBA/1 mice with homologous type II collagen is a valuable model for testing disease-modifying antiarthritic drugs. Six-week-old male DBA/1 mice were immunized with murine type II collagen in Freund's complete adjuvant, resulting in a chronic relapsing polyarthritis in >80% of the mice 4 weeks after immunization. At the onset of clinical arthritis, mice were treated for 4 weeks with different treatments, including anti-tumor necrosis factor (anti-TNF) and antiinterleukin-12 (anti-IL-12) antibodies, salbutamol, or indomethacin. Alternatively, treatment was administered as a pulse at the beginning of clinical arthritis. Pulse treatments tested included anti-CD3 in combination with anti-TNF, anti-TNF alone, and anti-CD4, either alone or in combination with anti-TNF. After 4 weeks of arthritis, mice were killed and hind paws were assessed histologically for joint damage. Anti-TNF and salbutamol both suppressed clinical arthritis more effectively than indomethacin and, moreover, protected the joints from damage, whereas indomethacin did not. Anti-IL-12 treatment initiated after the onset of clinical symptoms accelerated disease. Pulse therapy with anti-CD3 plus anti-TNF was found to induce remission, clinically as well as histologically, whereas a pulse with either anti-CD4, anti-TNF, or the combination of anti-CD4 plus anti-TNF was less effective. Chronic relapsing homologous collagen-induced arthritis is a valuable model for identifying remission-inducing antiarthritic drugs and has predictive value with respect to their joint-protective potency.

Treatment of rheumatoid arthritis: new therapeutic approaches with biological agents.

Rheumatoid arthritis is a chronic polyarthritis leading to joint destruction and remarkable disability. Current therapies have various degrees of efficacy, but toxicity frequently limits their long-term use. Furthermore, treatment of refractory rheumatoid arthritis includes increasing disease-modifying antirheumatic drugs dosage, using combination therapy, and adding or increasing the posology of corticosteroids. Although the etiology of the disease remains unknown, our increasing knowledge of the mechanisms underlying pathogenic events in rheumatoid synovitis, has provided opportunities to specifically target cell surface markers or cytokines involved in the inflammatory response. The objective of this review is to describe the different therapeutic approaches with biological agents that are either being utilized or are under development. Some of these products reflect the evolving capacity for the biotechnology industry to synthesize and humanize therapeutic agents: anti-tumor necrosis factor (TNF) alpha monoclonal antibodies (MoAb) and recombinant TNF-receptor construct appear to be validated tools. These treatments alone, or in combination with methotrexate are very effective in rheumatoid patients. Data from clinical trials and issues related to mechanisms of action, potential toxicity, and future perspectives for these novel therapeutic options are considered in this review. Anti-cytokine treatment include other interesting approaches to interfere with on-going inflammatory processes, such as the use of recombinant human interleukin (IL)1 receptor antagonist, or recombinant human IL10. T cell constimulatory blockade, induction of apoptosis in the synovial tissue, and gene therapy could represent future strategies in rheumatoid disease.

Joint swelling as a predictor of death from cardiovascular disease in a population study of Pima Indians.

Markers of inflammation have recently been shown to be predictive of cardiovascular disease (CVD). Furthermore, the excess mortality in rheumatoid arthritis (RA), a disease characterized by chronic polyarthritis, is chiefly due to death from CVD. With this background, we studied the effect of inflammation, as reflected by the number of joints with soft tissue swelling, and rheumatoid factor (RF) seropositivity on CVD-related mortality. Mortality rates and rate ratios for all-cause and CVD-related deaths were computed in a longitudinal, population-based cohort of Pima Indians in Arizona from 1965 through 1994. Repeated health examinations were performed, involving systematic assessment of the features of RA, cardiovascular risk factors, serum titers of RF, as well as mortality. The cohort comprised 4,120 subjects (1,861 men, 2,259 women) who were examined an average of 3.5 times during a mean followup of 14 years. During the followup period, 182 CVD-related deaths ocurred. The age- and sex-adjusted CVD-related mortality rates increased significantly with the presence of a higher number of joints with soft tissue swelling (Ptrend = 0.04), and were 2.07 (95% confidence interval [95% CI] 1.30-3.31) times as high in those subjects who had 2 or more swollen joints as in those who had none. There were no significant additional effects on CVD-related mortality when seropositivity for RF or a previous diagnosis of RA were considered. In age- and sex-adjusted proportional hazards analyses, which were controlled for possible confounders, the effect of swollen joints remained significant (mortality rate ratio 1.33, 95% CI 1.04-1.71 per category increase [no swollen joints, 1 swollen joint, at least 2 swollen joints]). Joint swelling is a significant risk factor for CVD-related death, independent of other known risk factors including a diagnosis of RA. This finding supports the hypothesis that inflammatory mechanisms are important for the development of CVD.

Management of hepatitis C virus-related arthritis.

Hepatitis C virus (HCV) infection is often associated with extrahepatic manifestations among which arthropathy is common, affecting up to 20% of HCV-infected individuals. This arthropathy is to be distinguished from the more superficially prominent myalgias and fatigue. HCV-related arthritis is commonly presented as rheumatoid-like, symmetrical inflammatory polyarthritis involving mainly small joints, or, less commonly, as mono- or oligoarthritis, usually of the large joints. HCV arthritis usually runs a relatively benign course that, in contrast to 'true' rheumatoid arthritis (RA), is typically non-deforming and is not associated with articular bony erosions. In addition, unlike 'classic' RA, erythrocyte sedimentation rate is elevated only in about half of the patients and subcutaneous nodules are absent. In about two-thirds of the affected individuals morning stiffness may be severe, resolving after more than an hour. Several pathogenetic mechanisms may be involved: HCV arthritis may be part of the syndrome of mixed cryoglobulinaemia, or may be directly or indirectly mediated by HCV. Such possible, but yet not proven, mechanisms include direct invasion of synovial cells by the virus eliciting local inflammatory response, cytokine-induced disease or immune complex disease, particularly in genetically susceptible individuals. The diagnosis of HCV arthritis in patients with positive rheumatoid factor and chronic inflammatory polyarthritis may be difficult. Positive HCV antibody and HCV RNA, and the absence of bony erosions, subcutaneous nodules and antikeratin antibodies, may be useful in distinguishing between HCV-related arthritis and RA. The optimal treatment of HCV-related arthritis has not yet been established. Concerns may be raised regarding the use of immunosuppressive or potentially hepatotoxic drugs. However, it may be suggested that once the diagnosis of HCV-associated arthritis is made, combination antiviral treatment with interferon-alpha and ribavirin should be initiated as part of the therapeutic armamentarium. Low dose oral corticosteroids, nonsteroidal anti-inflammatory drugs, hydroxychloroquine or sulfasalazine in addition to the antiviral therapy can be used to control arthritis-related symptoms. Some patients may need long term anti-inflammatory treatment in various combinations, along with antiviral therapy. In patients with severe, disabling or life-threatening cryoglobulinaemia-related symptoms refractory to antiviral or anti-inflammatory treatment, high dose corticosteroids (including pulse therapy) and/or plasmapheresis may be needed.

Chronic relapsing homologous collagen-induced arthritis in DBA/1 mice as a model for testing disease-modifying and remission-inducing therapies

To test whether the chronic relapsing arthritis induced by immunizing DBA/1 mice with homologous type II collagen is a valuable model for testing disease-modifying antiarthritic drugs.Six-week-old male DBA/1 mice were immunized with murine type II collagen in Freund's complete adjuvant, resulting in a chronic relapsing polyarthritis in >80% of the mice 4 weeks after immunization. At the onset of clinical arthritis, mice were treated for 4 weeks with different treatments, including anti-tumor necrosis factor (anti-TNF) and antiinterleukin-12 (anti-IL-12) antibodies, salbutamol, or indomethacin. Alternatively, treatment was administered as a pulse at the beginning of clinical arthritis. Pulse treatments tested included anti-CD3 in combination with anti-TNF, anti-TNF alone, and anti-CD4, either alone or in combination with anti-TNF. After 4 weeks of arthritis, mice were killed and hind paws were assessed histologically for joint damage.Anti-TNF and salbutamol both suppressed clinical arthritis more effectively than indomethacin and, moreover, protected the joints from damage, whereas indomethacin did not. Anti-IL-12 treatment initiated after the onset of clinical symptoms accelerated disease. Pulse therapy with anti-CD3 plus anti-TNF was found to induce remission, clinically as well as histologically, whereas a pulse with either anti-CD4, anti-TNF, or the combination of anti-CD4 plus anti-TNF was less effective.Chronic relapsing homologous collagen-induced arthritis is a valuable model for identifying remission-inducing antiarthritic drugs and has predictive value with respect to their joint-protective potency.

Efficacy of Methylprednisolone pulse therapy versus Infliximab in the treatment of severe flares of chronic polyarthritis

Background : To compare short term efficacy of pulse intravenous (iv) Methylprednisolone (MP) versus Infiximab in flares of polyarthritis. Patients-methods : Observational study of consecutive patients admitted with flares of chronic polyarthritis. Treatment consisted of three iv doses of MP 1000 mg on alternate days (MP-group, n = 10) or of Infliximab will be 3 mg/kg at baseline, two, and six weeks later (I-group, n = 9). DMARD therapy was initiated/continued in all patients. Disease parameters at baseline (t = 0), two weeks (t = 1) and twelve weeks (t = 2) were compared by non-parametric testing. Results : Reductions in disease parameters at both t = 1 and t = 2, the occurrence of side effects and the proportion of patients reaching ACR 20, 50 or 70% response criteria were similar in both groups. Conclusion : Pulse MP resulted in a symptomatic response similar to Infliximab in our patients. The benefit of MP was observed for up to 3 months.

IL-4 VNTR gene polymorphism in chronic polyarthritis. The rare allele is associated with protection against destruction.

To evaluate the occurrence of variants of the interleukin 4 (IL-4) and IL-4 receptor (IL-4R) genes in patients with rheumatoid arthritis (RA) and their possible contribution to joint destruction. Allelic frequencies for polymorphisms in the IL-4 [variable number of tandem repeat (VNTR) polymorphism in intron 3] and IL-4 receptor alpha chain (transition at nucleotide 1902) genes were assessed in 335 RA patients and 104 controls. Clinical indices of disease activity, disability and joint destruction and plasma levels of IL-1beta, IL-1Ra and sCD23 were assessed to evaluate a possible functional effect. Carriage of the rare IL-4(2) allele was higher in patients with non-destructive RA (40%) than in those with destructive RA (22.3%; odds ratio = 1.9, 95% confidence interval 1. 1-3.5, P = 0.0006) and in controls (26%, P = 0.002). Patients positive for this rare allele had significantly less joint destruction, assessed by the Larsen wrist index (P = 0.004) and a lower erythrocyte sedimentation rate (P = 0.04). A significantly higher carriage rate of IL-4(2) was seen in HLA-DR4/DR1(-) patients with non-destructive RA than in those with destructive RA. The IL-4 receptor polymorphism was not over-represented. Plasma levels of IL-1beta, IL-1Ra and sCD23, known to be modified by IL-4, were not different in individuals having different alleles. This IL-4 VNTR gene polymorphism may be a protective factor for severe joint destruction in RA that could be used as a prognostic marker early in the course of the disease.

Descriptive Epidemiology of Chronic Disease of Calves in a Western Canadian Feedlot

A pattern of chronic disease has been recognized in fall-placed, weaned beef calves in western Canadian feedlots. Affected calves become "non-responders" to antibiotic therapy, with weight loss, chronic pyrexia and/or lameness. These calves are moved to a chronic pen for a period of convalescence. This study is describes this pattern of chronic disease in terms of morbidity, days on feed, weight change, and mortality. Its second objective is to determine the association between bovine virus diarrhea virus (BVDV) and Mycoplasma bovis infection and chronic pneumonia and/or polyarthritis in feedlot calves.