Disease Activity Score 28-ESR bears a similar relationship to treatment decisions across different rheumatologists, but misclassification is too frequent to replace physician judgement.

OBJECTIVES: To determine whether physician factors are associated with disease activity status in RA, independently of 28-joint disease activity score (DAS28)-ESR and to re-evaluate DAS28-ESR misclassification rates for identifying active disease in usual practice. METHODS: A prospective observational study of outpatients with RA seen by 17 rheumatologists across New Zealand. Active disease was defined by an increase in therapy together with a reason of 'active disease'; very low disease activity was defined by a decrease in therapy together with a reason of 'patient well'. The independent physician effect was assessed using logistic regression. Sensitivity and specificity of current DAS28-ESR thresholds were calculated. RESULTS: In 511 patients, 178 had active disease, 220 had low disease activity, 37 had very low disease activity and 76 had uncertain disease activity status. There was no independent effect of physician upon active disease status (P = 0.16) with DAS28-ESR [(OR) 3.7] explaining around 50% of the variability in active disease status. There was a trend towards an independent effect of physician upon very low disease activity status (P = 0.06) and greater variability in the distribution of DAS28-ESR for patients in very low disease activity. DAS28-ESR thresholds showed a significant risk of misclassification for active disease. CONCLUSIONS: DAS28-ESR discriminates satisfactorily between groups of patients with active and non-active disease, with no evidence of additional physician-specific factors to explain disease activity status. However, DAS28-ESR is not as good for discriminating remission from non-remission status. There are appreciable probabilities of misclassification error, which make DAS28-ESR inappropriate as a sole guide for treatment decisions.

Preparation, characterization, and performance of magnetic iron-carbon composite microparticles for chemotherapy.

Magnetic microcarrier particles useful for delivering chemotherapeutic drug molecules are described. The particles are formed by joint deformation of iron and carbon in a ball mill. Physical, chemical, and functional characterization has been carried out on the particles. Physical characteristics include microscopy, particle size analysis (0.5-5 microm), surface area (250 m2/g), water vapor adsorption isotherm (hydrophobic surface), and analysis of the iron-carbon interface by Mössbauer spectroscopy, X-ray diffraction, and differential thermal analysis. Chemical analysis was used to identify elements in the particles other than carbon and iron. Functional characteristics measured included the particles' ability to adsorb and desorb doxorubicin, cytotoxicity, and their magnetic susceptibility.

Electrokinetic isolation of vesicles and ribosomes derived from Serratia marcescens.

Ribosomes and vesicles derived from the bacterium Serratia marcescens were separated from each other and from solubles using density gradient electrophoresis. Transport relationships were used to determine the electrophoretic mobilities of the particles. The effects of convection, sedimentation and diffusion were found to be negligible. The electrophoretic mobility obtained for the ribosome peak is -7 x 10(-5) cm2/(V.s). Under appropriate conditions, two vesicles peaks were obtained, the first with a mobility of -4 x 10(-5) cm2/(V.s) and the second with -9 x 10(-6) cm2/(V.s). This information can be used to predict the resolution of the separands in large-scale electrophoretic separations.

The determination of thiomalate in physiological fluids by high-performance liquid chromatography and electrochemical detection.

Methods are described for the determination of free thiomalate in the plasma and urine of patients receiving the anti-rheumatic drug sodium aurothiomalate. Thiomalate is separated by reversed-phase chromatography and detected using a gold electrochemical cell. Plasma analyses require maximal sensitivity while urine estimations require selectivity rather than sensitivity: different phosphate buffer-methanol eluents and electrode potentials are used. On-column sensitivity for thiomalate is 40 fmol injected.

Effect of carbohydrate ingestion on performance of non-fasted cyclists during a simulated 80-mile time trial.

The purpose of this study was to determine the effect of carbohydrate supplementation on finishing time of a realistically simulated 80 mile bicycle time trial. Fourteen trained cyclists pedalled at self-selected pace on their own bicycles on windload simulators. Two trials were performed one week apart. Each trial was preceded by two days of prescribed diet, with a final feeding 3-4 h prior to exercise. Following each 10 mile segment, subjects ingested either a non-caloric placebo (PL) or the carbohydrate maltodextrin supplement (MD; 5% maltodextrin +2% fructose) at dosage of 0.25 g.kg-1 body weight (mean intake rate, total: 37 g.h-1, 148 g) in a double blind, counter-balanced design. Mean (+/- SEM) finishing times were faster by 5% with MD (241.0 +/- 2.1 minutes versus 253.2 +/- 2.1 minutes), p < 0.05. With MD, serum glucose levels rose sharply after 40 miles and were significantly higher than PL (p < 0.05). Final glucose values were 6.0 +/- 0.2 mmol.l-1 and 4.1 +/- 0.2 mmol.l-1 for MD and PL, respectively. With MD, free fatty acid levels were significantly lower (p < 0.05), and riders sustained higher average intensity over the entire distance. At the finish, intensities were 64.7 +/- 1.9% VO2max and 55.3 +/- 1.9% VO2max for GP and PL, respectively. Mean carbohydrate oxidation was significantly higher (p < 0.05) for MD, 2.01 +/- 0.2 g.min-1 and 1.64 +/- 0.2 g.min-1 for MD and PL, respectively. These data show that ingestion of MD, during ultraendurance exercise, in comparison to PL, decreases the time to finish a self-paced bicycle time trial.

Spontaneous rupture of all three extensor tendons to the thumb in rheumatoid arthritis.

A case of spontaneous rupture of all three extensor tendons to the thumb in a patient with Rheumatoid Arthritis is described.

HLA B27 negative ankylosing spondylitis--a rare condition.

New strict criteria have recently been suggested for the definition of HLA B27 negative ankylosing spondylitis, which show it to be less common than was previously thought. We report two cases which conform to the new criteria, together with details of family studies. The use of these criteria in future studies of B27 negative disease is discussed.

Failure of oral thiomalate to act as an alternative to intramuscular gold in rheumatoid arthritis.

Ten patients with active rheumatoid arthritis (RA) were entered into a pilot study to evaluate the effectiveness of thiomalic acid as a disease modifying agent and to assess its toxicity. Oral thiomalic acid (100 mg) was given daily for up to six months. Changes in disease activity were recorded monthly and all side effects noted. No patient recorded any improvement in subjective well being, pain score, or duration of early morning stiffness. No significant change occurred in articular index or haemoglobin (Hb); the erythrocyte sedimentation rate (ESR) showed a tendency to increase. Only three patients completed six months' treatment; six withdrew because of toxic reactions (three with rashes and three with severe gastrointestinal upset) and one because of lack of effect. Thiomalic acid alone appears to have no significant antirheumatic activity and is associated with an unacceptably high incidence of adverse reactions.

The determination of cysteamine in physiological fluids by HPLC with electrochemical detection.

Cysteamine, an amino thiol, was separated by rapid isocratic cation exchange chromatography and detected by electrochemical oxidation at a platinum electrode maintained at +0.45 V relative to an Ag/AgCl reference electrode. Eluent pH and electrode working potentials were optimized and the effects of alternative buffers and organic modifiers have been examined. On column sensitivity for cysteamine was 1.5 pmol at a signal-to-noise ratio of 5. Although the specificity was good, plasma samples required maximal sensitivity whereas urine samples required greater selectivity, which was achieved by use of lower working potentials. Cysteamine concentrations were determined in serial samples of plasma and urine from volunteers who had received a single oral dose of 200 mg of the drug. Cysteamine was rapidly oxidized in vivo, and detection required prior reduction with dithiothreitol before analysis.

Free thiomalate levels in patients with rheumatoid arthritis treated with disodium aurothiomalate: relationship to clinical outcome of therapy.

Sixteen patients with seropositive rheumatoid arthritis were treated with 20 mg disodium aurothiomalate (Myocrisin) weekly for six months. Disease activity was assessed before and after treatment. Plasma profiles and urinary excretion of free thiomalate were measured in all patients after the initial injection and again at six months in the 12 patients remaining on therapy. No difference was found in plasma levels or urinary excretion of free thiomalate between patients who responded to treatment or who developed toxic reactions and those who did not.

Free thiomalate in plasma and urine of patients receiving sodium aurothiomalate.

Free thiomalate is measureable in the plasma and urine of patients with rheumatoid arthritis receiving sodium aurothiomalate (Myocrisin). Plasma concentrations and urinary excretion of free thiomalate were measured in 8 patients by high-performance liquid chromatography and electrochemical detection. After an initial intramuscular dose of 20 mg sodium aurothiomalate, free thiomalate was detected in plasma within 15 min, peak levels of up to 600 nmol/l occurring at 30 min. Plasma levels declined rapidly thereafter. During the first 24 h between 2 and 16% of the injected dose of aurothiomalate was recovered in the urine as free thiomalate, maximum excretion occurring during the first hour.

Menstrual cyclicity of finger joint size and grip strength in patients with rheumatoid arthritis.

Daily measurements of finger joint size, grip strength, and body weight have been made throughout 2 complete menstrual cycles in 7 female patients with rheumatoid arthritis and 6 healthy female controls. Sine wave analysis showed significant individual cyclical rhythms (p less than 0.05) for finger joint size (5 patients, 4 controls), nude weight (5 patients, 3 controls), and grip strength (4 patients, 3 controls). In addition analysis of group data, on the assumption of a 28-day cycle, showed a significant cycle for grip strength in the rheumatoid patients, with a nadir at 28 days. In the normal subjects much of the cyclical variation in finger joint size could be explained by changes in weight (median 49.5%), but this was not so in patients with rheumatoid arthritis (median 2.8%). These findings suggest the existence of a cyclical variation in disease activity in rheumatoid arthritis.

Structural requirements for activity of certain 'specific' antirheumatic drugs: more than a simple thiol group?

The relationship between chemical structure and the clinical activity and toxicity of several second-line antirheumatic drugs is examined. The presence of a thiol group in many of these agents has previously been noted, but most of the compounds additionally either possess, or form metabolites containing, the ethanethiol backbone or a similar ring structure. This applies not only to penicillamine and disodium aurothiomalate but also to thiola , 5- thiopyridoxine , levamisole and captopril. The presence of free circulating thiols has recently been shown for several of these compounds including free thiomalate in the case of disodium aurothiomalate, which on a molar basis is the most potent agent of all. Further study of thiomalate and related compounds in vitro and in vivo may clarify the pathogenesis of rheumatoid arthritis as well as allowing the development of more effective and less toxic second-line agents.

Fusion of the first metatarsophalangeal joint in forefoot arthroplasty.

Forefoot arthroplasty is often recommended for the management of metatarsalgia secondary to rheumatoid arthritis. Concurrently, the first metatarsophalangeal (MP) joint can be fused rather than excised. The results in 37 patients with 64 arthroplasty operations (34 with fusion and 30 with excision of the first joint) show that fusion produced a better cosmetic appearance of the foot, facilitated fitting with normal shoes, and improved overall balance. Pedobarograph measurements during gait indicated that relatively more weight was transmitted through the medial ray when the first metatarsophalangeal joint was fused. Residual pain in the foot was often caused by irregular trimming of the metatarsals. There was no difference in relief of pain between fused and unfused patients. Failure of fusion at the first metatarsophalangeal joint generally was painless. Radiologic degeneration of the interphalangeal (IP) joint of the great toe was relatively common following fusion. MP joint fusion is inadvisable if there is already disease in the IP joint.

Circulating thiomalate after administration of disodium aurothiomalate: impurity or active metabolite?

During studies of the metabolism of disodium aurothiomalate in patients with rheumatoid arthritis we have found that its pharmaceutical preparation. Myocrisin, contains 4 to 8% of free thiomalate. To establish whether the free thiomalate previously reported in plasma and urine of patients receiving Myocrisin is a true metabolite or results from this impurity, we prepared aurothiomalate containing 0.1% thiomalate. Intramuscular injection of the purified drug to 2 healthy subjects produced easily detectable levels of thiomalate in both plasma and urine; 7.7 and 9.8% respectively of the doses given were recovered in urine as free thomalate within 4 h. Thus, dissociation of disodium aurothiomalate does occur in vivo, releasing both gold and free thiomalate as potentially active forms.

Long-term corticosteroids and cervical subluxation in non-rheumatoid patients.

Forty-five non-rheumatoid patients with chronic chest disease were examined radiographically for evidence of cervical subluxation. Twenty-six patients had received continuous corticosteroids for periods of between two and 20 years. The remainder (19 patients) had never been treated with steroids and acted as controls. There was no difference in atlanto-axial distance between the steroid-treated and control groups and in no patient did this measurement exceed 3 mm. However, subaxial subluxation was significantly increased in the steroid-treated group, directly related to the duration of steroid therapy (P less than 0.025).

Juvenile chronic arthritis and Wegener's granulomatosis.

We present a case of Wegener's granulomatosis in a teenage boy with systemic onset juvenile chronic arthritis. We discuss the implication of these two uncommon conditions coexisting in one patient. The recent characterization of the antineutrophil cytoplasmic antibody (ANCA) as a marker of small vessel vasculitis has helped in the differential diagnosis of pulmonary renal syndromes.

Class specific rheumatoid factors in rheumatoid arthritis: response to chrysotherapy and relationship to disease activity.

IgG rheumatoid factors (RF) may play an important role in the pathogenesis of rheumatoid arthritis (RA). Our study investigates the relationship between class specific RF levels measured by radioimmunoassay and disease activity in patients with RA undergoing chrysotherapy. Nineteen patients were treated with 20 mg disodium aurothiomalate weekly for 6 months. Rheumatoid disease activity was assessed before and after 6 months' treatment and the level of IgG, IgA and IgM RF measured. There were significant falls in disease activity (p less than 0.005), IgA RF (p less than 0.005) IgG RF (p less than 0.005) and SCAT (p less than 0.025), but not IgM RF, over the 6 month treatment period. No correlation was found between absolute levels of IgA, IgG or IgM RF and disease activity before or after 6 months' therapy but there was a highly significant linear correlation between reduction in IgG RF levels and fall in disease activity (r = 0.642, p less than 0.005) with treatment.