Dynamic exercise therapy in rheumatoid arthritis: a systematic review

The aim of this systematic review was to determine the effectiveness of dynamic exercise therapy in improving joint mobility, muscle strength, aerobic capacity and daily functioning in patients with rheumatoid arthritis (RA). In addition, possible unwanted effects such as an increase in pain, disease activity and radiological progression were studied. A computer-aided search of the MEDLINE, Embase and SCISEARCH databases was performed to identify controlled trials on the effect of exercise therapy. Randomized trials were selected on the effect of dynamic exercise therapy in RA patients with an exercise programme fulfilling the following criteria: (a) intensity level such that heart rates exceeded 60% of maximal heart rate during at least 20 min; (b) exercise frequency > or = 2 a week; and (c) duration of intervention > or = 6 weeks. Two blinded reviewers independently selected eligible studies, rated the methodological quality and extracted data. Six out of 30 identified controlled trials met the inclusion criteria. Four of the six included studies fulfilled > or = 7/10 methodological criteria. Because of heterogeneity in outcome measures, data could not be pooled. The results suggest that dynamic exercise therapy is effective in increasing aerobic capacity and muscle strength. No detrimental effects on disease activity and pain were observed. The effects of dynamic exercise therapy on functional ability and radiological progression are unclear. It is concluded that dynamic exercise therapy has a positive effect on physical capacity. Research on the long-term effect of dynamic exercise therapy on radiological progression and functional ability is needed.     

Methotrexate in juvenile rheumatoid arthritis. Evidence of age dependent pharmacokinetics

Children with juvenile rheumatoid arthritis (JRA) have been reported to require higher doses (per kg body weight) of methotrexate (MTX) than adults with rheumatoid arthritis to control their disease. The purpose of the present study was to characterise the plasma pharmacokinetics of MTX and its major metabolite, 7-hydroxymethotrexate (7-OHMTX) in children, and to compare the results with those previously obtained in adults. Thirteen patients (age 5-16 y) with JRA (median disease duration 5.5 y) were studied after once weekly oral administration of MTX (median 0.21 mg.kg-1). The analytical method was sufficiently sensitive to permit determination of plasma and urinary concentrations of MTX and 7-OHMTX during the entire dose interval in most of the patients. The dose normalized area under the plasma concentration versus time-curve (AUC) of MTX increased with the age of the children and was lower than previously found in adults. The dose normalized AUC of 7-OHMTX was not dependent on age. No correlation was found between the AUCs of MTX and 7-OHMTX. The results suggest that the age-dependence of the pharmacokinetics of MTX might explain the observation that at least some children require higher doses of MTX than adults to obtain a sufficient therapeutic effect.     

Methotrexate in the treatment of juvenile rheumatoid arthritis and other pediatric rheumatoid and nonrheumatic disorders

The goal of treatment for juvenile rheumatoid arthritis (JRA) and other pediatric rheumatic disorders is to minimize joint destruction, pain, and deformity and to maximize all aspects of growth and development. Oral and injectable methotrexate are now often given early in the treatment of JRA, childhood dermatomyositis, difficult-to-control arthritis in the pediatric spondyloarthropathies, SLE, sarcoidosis, several of the vasculopathies, and idiopathic iritis. Weekly low-dose MTX has become a mainstay of long-term improved control of these disorders, and is associated with strikingly few documented long-term side effects. Dosages, pharmacology, side effects, efficacy, and treatment strategies are discussed. Although formal studies are lacking, MTX for the pediatric rheumatic disorders seems to be associated with less frequent physician visits, lower total costs, improved function, and fewer late reconstructive surgeries.     

Methotrexate disposition following concomitant administration of ketoprofen, piroxicam and flurbiprofen in patients with rheumatoid arthritis

We report an unusual case of vulvar acantholytic dermatosis with features of pemphigus vegetans in a 22-year-old Indian girl who presented with a "warty" lesion in her left labium majus. Following excision of this lesion, she presented with 2 localized recurrent lesions on the left and right labia majora about 2 1/2 years later which were also excised. All 3 biopsies showed histological features typical of pemphigus which included extensive suprabasal acantholysis with bullae formation, prominent villus-like processes at the base of the bullae, focal hyperkeratosis and papillomatosis, and the occasional mixed neutrophil and eosinophilic intraepidermal abscess. IgG and C3 immunofluorescence was positive in the intercellular spaces of the epidermis. These lesions, which probably represent a form of pemphigus vegetans, have not been previously reported as a cause of localized vulvar acantholytic dermatosis.     

Drug-combination therapy of rheumatoid arthritis

The cytochromes c are a useful model for the study of the pathways and mechanisms of assembly of the cofactor-containing components of energy transducing membranes. Genetic analyses have identified proteins that are required for the assembly of c-type cytochromes in mitochondria, bacteria and chloroplasts. The components of the pathway operating in fungal and animal mitochondria, i.e. the cytochrome (cyt) c and c1 heme lyases in the intermembrane space, were identified over a decade ago through the study of cytochrome deficiencies in Neurospora crassa and Saccharomyces cerevisiae. More recently, a large number of membrane or membrane-associated components were identified in various alpha- and gamma-proteobacteria as c-type cytochrome assembly factors; they comprise an assembly pathway that is evolutionarily and mechanistically distinct from that in fungal and animal mitochondria. The components function not only in the lyase reaction but also in the delivery and maintenance of the substrates in a state that is suitable for reaction in the bacterial periplasm. Yet a third pathway is required for cytochrome maturation in chloroplasts. Genetic analyses of Chlamydomonas reinhardtii ccs mutants, which are pleiotropically deficient in both the membrane-anchored cytochrome f and the soluble cytochrome c6, revealed a minimum of six loci, plastid ccsA and nuclear CCS1 through CCS5, that are required for the conversion of the chloroplast apocytochromes to their respective holo forms. Sequence analysis of the cloned ccsA and Ccs1 genes indicates that the predicted protein products are integral membrane proteins with homologues in cyanobacteria, some gram-positive bacteria (Bacillus subtilis, Mycobacterium spp.), beta-proteobacteria (Neisseria spp.) and an epsilon-proteobacterium (Helicobacter pylori). CcsA and Ccs1 require each other for accumulation in vivo and are therefore proposed to function in a complex, possibly with the products of some of the other CCS loci. A tryptophan-rich motif, which has been proposed to represent a heme binding site in bacterial cytochrome biogenesis proteins (CcmC and CcmF), is functionally important in plastid CcsA. As is the case for CcmC and CcmF, the tryptophan-rich sequence is predicted to occur in a loop on the p-side of the membrane, where the heme attachment reaction occurs. Conserved histidine residues in the CcsA and Ccs1 may serve as ligands to the heme iron. A multiple alignment of the tryptophan-rich regions of the CcsA-, CcmC- and CcmF-like sequences in the genome databases indicates that they represent three different families.     

Combination therapy of rheumatoid arthritis

The prevalence of rheumatoid arthritis (RA) is about 0.5-1%. The disease course is variable, but RA causes substantial morbidity and mortality. The effect of conventional therapy for RA, i.e. nonsteroidal antiinflammatory drugs (NSAID), glucocorticosteroids and Slow Acting Anti-Rheumatic Drugs (SAARD) including methotrexate, gold salts, anti-malarials, d-penicillamine and salazopyrine, is often suboptimal. Since the aim of treatment is a complete remission, combination therapy, i.e. treatment with two or more SAARDs, may be feasible since an additive/synergistic effect may be obtained. In this paper the literature about the effectiveness and toxicity of combination therapy is reviewed. Only a few randomized, clinically controlled trials have been published. None of them have documented that gold salts, d-penicillamine and azathioprine in combination with other SAARDs are better than monotherapy. However, recent trials have indicated that methotrexate in combination with salazopyrine and hydroxychloroquine or in combination with cyclosporine may cause a better therapeutic effect than methotrexate alone, without additional toxicity. Long term studies of the effect of combination therapy are not yet available.     

Methotrexate in juvenile rheumatoid arthritis. Do the benefits outweigh the risks?

Juvenile rheumatoid arthritis (JRA) is a heterogeneous group of autoimmune diseases resulting in chronic idiopathic peripheral arthritis. The aetiology of JRA is unclear, and current pharmacotherapy is ameliorative rather than curative. Nonsteroidal anti-inflammatory drugs are given initially, but only one-third to one-fourth of patients are managed adequately with these agents. Advanced therapeutic drugs, frequently referred to as disease-modifying antirheumatic drugs or second-line agents, are given to the child with aggressive or resistant disease. Among these, the antimetabolite methotrexate has proven to be the most effective in alleviating articular disease manifestations and reducing laboratory parameters of inflammation. When given orally in low dosages (10 to 15 mg/m2/week), methotrexate is well tolerated, without evidence of substantial bone marrow suppression or severe hepatotoxicity. Extensive long term tolerability data are not yet available for children, but longitudinal studies in adult patients with rheumatoid arthritis suggest that the drug may be given safely for extended periods in many patients. Paediatric rheumatologists are beginning to give higher dosages of methotrexate (up to 1 mg/kg/week) parenterally with some success. The long term consequences of higher dose methotrexate in children are unknown. Methotrexate has now become, and will probably remain for some time, the drug of first choice for children with recalcitrant JRA.     

Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis

OBJECTIVES: Herein we describe an additional case of myelolipoma of the adrenal gland, an uncommon tumor of the adrenal cortex, that had been incidentally discovered during abdominal US evaluation of the biliary tree. The clinical features, diagnosis and treatment of the condition are discussed. METHODS: Surgical treatment of the biliary tree and myelolipoma was performed through a Chevron transversal incision during the same surgical session. RESULTS: Surgery achieved good results and the postoperative course was unremarkable. CONCLUSIONS: Myelolipoma is a benign nonfunctioning tumor of the adrenal cortex comprised of adipose and hematopoietic tissue. It is usually asymptomatic and incidentally discovered during diagnostic evaluation for other pathologies. The diagnosis is made by US, CT and MRI. There is no agreement on whether surgical treatment is warranted.     

Pathways to gene therapy in rheumatoid arthritis

OBJECTIVE: To document a cumulative experience with removal of the Telectronics 330-801 Accufix atrial lead after it was withdrawn from the market. DESIGN: We reviewed our results with 96 attempted lead extraction procedures through Dec. 1, 1995. MATERIAL AND METHODS: All patients underwent preoperative assessment, including fluoroscopic screening of the lead. Patients had blood typing and screening done before the extraction procedure, and extractions were performed with cardiac surgical intervention available. Pacing dependence was assessed to determine the need for temporary pacing. RESULTS: The mean patient age was 65.7 +/- 1.6 years and the mean duration of lead implantation was 31.0 +/- 1.4 months. Of the 96 lead extractions attempted, 94 were successful. Of the 96 cases, the retention wires were normal in 29, fractured without protrusion in 34, and fractured with protrusion in 33. Fifty-three leads were removed with use of simple traction only, and seven leads were removed by using a locking stylet and telescoping sheaths. The Cook workstation was used in the removal of 32 leads through the femoral vein; in 1 of these 32 patients, the retention wire was removed before lead extraction. The retention wire was removed but the lead was left intact in one patient. One lead was removed during an opertive maze procedure. Associated complications were minimal. CONCLUSION: Although lead extraction is a potentially fatal procedure, the Telectronics 330-801 Accufix atrial lead can be extracted safely with minimal morbidity when performed by experienced personnel.     

Contact allergy to gold and gold therapy in patients with rheumatoid arthritis

Patients with rheumatoid arthritis were investigated for contact allergy to gold in connection with treatment with gold preparations. There were 57 patients with rheumatoid arthritis previously treated with gold, with or without cutaneous side-effects, as well as 20 patients intended for such treatment; all were exposed to patch and intradermal tests with gold sodium thiosulfate, gold sodium thiomalate and auranofin. Contact allergy to gold was demonstrated in 8 out of 77 patients (10.4%). In the retrospective material, gold allergy was found in 1.8%, in the prospective material in 35.0%. Contact allergy to gold is very frequent among patients with rheumatoid arthritis before gold therapy. In order to avoid early hypersensitivity reactions skin tests should be carried out before gold therapy is instituted.