Methotrexate: long-term safety and efficacy in an Australian consultant rheumatology practice.

BACKGROUND: The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment. METHODS: A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18-year period. The primary outcome was time to cessation of MTX. RESULTS: Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity-related discontinuation occurred in 93 patients (11.8%) and due to non-adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57-0.96; P = 0.014); patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42-0.74; P < 0.001). Being of the male sex aged more than 60 years and having a non-RA diagnosis predisposed to stopping MTX earlier. CONCLUSION: MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. MTX has a low toxicity profile and this study stresses the need to re-evaluate and revise the current monitoring guidelines.

Interlaboratory study of a test method measuring total volatile organic compound content of consumer products.

Consumer products are potentially significant sources of volatile organic compounds (VOCs), which are precursors to the formation of ozone in photochemical smog. To address the problem of ozone formation in ambient air, the U.S. Environmental Protection Agency (EPA) has been involved in the development of test methods for measuring the VOC content of consumer products. This paper describes results of an interlaboratory study to estimate the repeatability (precision of analyses performed by a single laboratory) and reproducibility (precision of analyses performed by different laboratories) of the consumer products' VOC measurement method based on EPA Method 24 (for VOCs in surface coatings). The mean method repeatability was 2.7 wt% VOC, and the mean method reproducibility was 4.8 wt% VOC. Method repeatability ranged from 0.2 to 4.4 wt% VOC, and reproducibility ranged from 0.6 to 11.9 weight percent VOC. The precision of the VOC method for consumer products is similar to the precision of EPA Method 24 for surface coatings.

Polymorphonuclear motility: measurement by computer-linked image analysis.

Most methods of measuring neutrophil motility provide information mainly about the performance of a small proportion of the fastest moving cells. Application of a computer-linked image analysis technique, using the "Quantimet," provides a convenient, automated method of measuring the motility of the whole cell population. This makes it possible to test whether changes in motility represent a homogeneous alteration affecting all cells or a change in the numbers or performance of a subset of cells. In this study the neutrophils from patients with uncomplicated rheumatoid arthritis were found to perform similarly to normals, while cells from patients with Felty's syndrome were markedly slower. This was an overall, homogeneous slowing of the whole cell population, not due to a loss of fast moving cells.

Lysozyme-promoted association of protein I molecules in the outer membrane of Escherichia coli.

Incubation of whole envelopes prepared from sonically oscillated Escherichia coli K-12 cultures with lysozyme in vitro resulted in the appearance of a protein species with an apparent molecular weight double that of outer membrane protein I. Similar dimers were also detected in purified outer membranes and whole envelopes from lysozyme-induced spheroplasts of E. coli K-12. This was confirmed by two-dimensional electrophoresis in which the dimers were resolved in the second dimension to run as single polypeptides of protein I. Formation of dimers was correlated with peptidoglycan degradation, but the ability of protein I molecules to associate may vary between strains of E. coli, since dimers were found only in outer membranes from E. coli W7. We suggest that extensive degradation of peptidoglycan leads to nonspecific formation of protein I aggregates, but that these aggregates do not occur in vivo.

Scleroderma and silicone breast implants.

A 43-yr-old caucasian female presented in July 1992 with an explosive onset of diffuse scleroderma following general anaesthesia for orthopaedic surgery. Her environmental exposures included silicone breast prosthetic surgery and silica exposure, both preceding development of scleroderma. She was DR5-negative, DRw52 positive. All currently available literature relating to breast implants and scleroderma is reviewed and the conclusion drawn that, for currently documented US data, there is no evidence to suggest that patients having had breast augmentation have rates of scleroderma higher than expected to chance alone. However the cause-effect relationship between silicone and scleroderma/other connective tissue disease requires, not just anecdotal reports, but a rigorously designed study.

Chronic sternal wound infection and endocarditis with Coxiella burnetii.

Chronic Q fever is most commonly associated with culture-negative endocarditis and less frequently with infection of vascular grafts, infection of aneurysms, hepatitis, pulmonary disease, osteomyelitis, and neurological abnormalities. We report a case of chronic sternal wound infection, polyclonal gammopathy, and mixed cryoglobulinemia in which Q fever endocarditis was subsequently diagnosed. Polymerase chain reaction analysis of the wound tissue was positive for Coxiella burnetii DNA, and treatment of the endocarditis resulted in prompt healing of the wound. Chronic Q fever can occur without epidemiological risk factors for C. burnetii exposure and can produce multisystem inflammatory dysfunction, aberrations of the immune system, and persistent wound infections.

Polymorphonuclear cell function in rheumatoid arthritis and in Felty's syndrome.

Tests for polymorphonuclear cell (PMN) chemotaxis, adherence, and electrophoretic mobility (EPM) were carried out on blood PMN isolated from 27 normal subjects, 16 patients with uncomplicated rheumatoid arthritis (RA), and 9 patients with Felty's syndrome. Chemotaxis was measured by a modification of the Boyden chamber technique, adherence by retention of cells on nylon fibre columns, and EPM in a cylindrical electrophoretic assembly. There was no significant difference between the chemotactic migration of normal and rheumatoid PMN as assessed by the leading front measurement. However, PMN from patients with Felty's syndrome showed significantly reduced chemotaxis (P less than 0.001). Computerised image analysis showed this impaired migration to be due to an overall reduction in cell motility rather than loss of a subset cells. Activated serum from patients with RA and Felty's syndrome were as good chemoattractants as activated pooled AB serum. There was no significant difference in the adhesiveness of PMN from normal persons and rheumatoid patients, though PMN from patients with Felty's syndrome did show a trend to lower adhesiveness. Both RA and Felty's syndrome patients had an increase in the proportion of PMN of lower surface charge than controls. Direct correlations were observed between cells of high surface charge and nonadhesiveness.

Secondary screening for osteoporosis in patients admitted with minimal-trauma fracture to a major teaching hospital.

AIMS: The aim of the present study was to determine: (i) the prevalence of the investigation and treatment of osteoporosis in patients admitted to hospital with a minimal-trauma fracture, (ii) the prevalence of osteoporosis using bone mineral density assessment by dual X-ray absorptiometry (DEXA) in such patients and (iii) a clinical pathway for the management of osteoporosis in such patients. METHODS: A cross-sectional study was undertaken involving all patients admitted with a fracture to Westmead Hospital, Sydney, Australia, between January 1999 and June 2000 (n = 327). Of these, 264 were excluded because of: (i) the fracture following significant trauma (n = 83), (ii) unavailability of medical records for review (n = 38), (iii) nursing home status (n = 37), (iv) previous malignancy (n = 18), (v) deceased (n = 11), (vi) recent osteoporosis screening and/or treatment (n = 18), (vii) refusal to participate (n = 37), (viii) uncontactable (n = 16) and (ix) inadequate English (n = 6). The remaining 63 patients underwent DEXA assessment and the following laboratory investigations: (i) liver function tests, (ii) urea, (iii) electrolytes, (iv) calcium, (v) phosphate, (vi) full blood count, (v) 25-hydroxyvitamin D level and (vi) thyroid-function tests. In men, levels of serum free testosterone, luteinizing hormone, follicle-stimulating hormone and prolactin were also obtained. RESULTS: Of the 63 study participants, 87% of the 47 women were either osteoporotic (T <-2.5) or osteopenic (-2.5

The effects of enteric coating of aspirin tablets on occult gastrointestinal blood loss.

The effect of enteric coating of aspirin tablets on the gastrointestinal blood loss associated with high dose aspirin therapy was investigated in 12 patients with rheumatoid arthritis. Occult blood loss was measured after labelling the patients' red blood cells with Cr51. Three salicylate preparations were used: enteric coated tablets of aspirin ("Rhusal", G.P. Laboratories, 7 x 650 mg per day), uncoated tablet cores of aspirin from the same batch (7 x 650 mg per day) and enteric coated tablets of sodium salicylate (7 x 600 mg and 1 x 300 mg per day). Daily blood loss during a salicylate-free period was (0.7 +/- 0.15 ml, mean +/- SE). Blood loss was significantly increased during dosage with all three salicylate preparations. Daily blood loss during dosage with the uncoated tablets of aspirin (5.3 +/- 0.3 ml) was significantly greater than during dosage with the enteric coated tablets of aspirin (2.3 +/- 0.3 ml) and enteric coated tablets of sodium salicylate (2.1 +/- 0.4 ml). The bioavailability of the salicylate preparations was studied in seven of the 12 patients. Mean plasma salicylate concentration two hours after the second daily dose during dosage with the enteric coated tablets of aspirin was 118 +/- 15 microgram/ml compared to 131 +/- 16 microgram/ml during dosage with the uncoated tablets. Urinary recoveries of the daily dosage of aspirin in the two formulations were also similar.

Postexposure prophylaxis against experimental inhalation anthrax.

Inhalation anthrax is a rare disease that is almost invariably fatal. This study determined whether a prolonged course of postexposure antibiotics with or without vaccination would protect monkeys exposed to a lethal aerosol dose of Bacillus anthracis when the antibiotic was discontinued. Beginning 1 day after exposure, groups of 10 animals were given penicillin, ciprofloxacin, doxycycline, doxycycline plus vaccination, vaccination alone, or saline. Antibiotics were administered for 30 days and then discontinued. Vaccine was given on days 1 and 15. Two animals died of causes other than anthrax and were not included in the statistical analysis. Nine of 10 controls and 8 of 10 animals given only vaccine died. Each antibiotic regimen completely protected animals while on therapy and provided significant long-term protection upon discontinuance of the drug (penicillin, 7 of 10 survived, P < .02; ciprofloxacin, 8 of 9 survived, P < .002; doxycycline, 9 of 10 survived, P < .002; doxycycline plus vaccination, 9 of 9 survived, P < .0002). Protection against rechallenge was provided by combining postexposure antibiotic treatment with vaccination.