The detection of raised levels of IgM to Proteus mirabilis in sera from patients with rheumatoid arthritis.

An analysis by ELISA of 100 rheumatoid factor (RF)-positive sera selected at random from a collection of sera from patients with various auto-immune diseases and joint pains, and 100 RF-negative sera from the same collection matched by patient age and gender, showed that the RF-positive sera had highly significantly (p < 0.0001) raised levels of IgM antibody, but not IgG antibody, to Proteus mirabilis over those of the RF-negative sera. This response was subsequently found to be associated with sera from patients who clinically had rheumatoid arthritis (RA). Sera from the RA patients had significantly greater amounts (p = 0.026) of IgM antibody to P. mirabilis than to the other organisms tested and these values were also highly significantly different (p < 0.0001) from P. mirabilis IgM antibody levels in matched RF-negative sera. Sera from RA patients also had significantly greater amounts of IgA to P. mirabilis (p < 0.0001) and greater amounts of IgM to Escherichia coli (p < 0.0001) and Klebsiella pneumoniae (p < 0.0001) than those in matched RF-negative sera. Other classes of antibody to these organisms and all classes of antibody to Pseudomonas aeruginosa were not raised in the sera of RA patients over those of RF-negative controls. The IgM response in RA patients was not specific for only one O serotype of P. mirabilis but was associated with all 11 different O serotypes of P. mirabilis tested and those of other Proteus spp. Moreover, the IgM antibodies to Proteus spp. appeared to be independent from C-reactive protein and RF.(ABSTRACT TRUNCATED AT 250 WORDS)

Penicillamine-induced ocular myasthenia gravis.

Two patients with rheumatoid arthritis (two women, 58 and 62 years old) developed reversible penicillamine-induced ocular myasthenia gravis. Both had the HLA-DR1 antigen, unlike most patients with idiopathic myasthenia gravis who show HLA-DR3, suggesting that penicillamine-induced myasthenia gravis and its idiopathic counterpart occur in patients with different genetic backgrounds. In both cases, cessation of drug treatment led to resolution of the symptoms.

A comparative trial of a controlled-release formulation of ketoprofen ('Oruvail') and a conventional capsule formulation of ketoprofen ('Orudis') in patients with osteoarthritis of the hip.

An open study was carried out in 46 patients with osteoarthritis of the hip to compare the efficacy and tolerance of treatment with ketoprofen given either as 100 mg capsules twice daily or as 2 capsules of 100 mg ketoprofen in a controlled-release formulation given once daily. The results of subjective and objective assessments before and during 3-months' treatment in the 48 patients who completed the trial showed both treatments produced improvement in all parameters, except for the time taken for inactivity stiffness to develop, and there was no significant difference between treatments in terms of efficacy. The controlled-release preparation, however, was significantly better tolerated than the ordinary capsule form. Minor haematological and biochemical changes during treatment were noted but these were not of clinical importance. Six patients, 2 receiving the controlled-release and 4 receiving the ordinary formulation of ketoprofen, were withdrawn because of lack of efficacy or unacceptable side-effects.

Evidence that patients with rheumatoid arthritis have asymptomatic 'non-significant' Proteus mirabilis bacteriuria more frequently than healthy controls.

OBJECTIVES: patients with rheumatoid arthritis (RA) are reported to have in their sera raised levels of antibody specific to Proteus mirabilis. The aim of the study was to verify this and to determine an explanation for it by investigating the frequency of P. mirabilis urinary tract infection in RA patients and matched controls. METHODS: freshly voided urine was examined for the presence, number and identity of infecting bacteria. The levels of antibody in blood and in urine of the IgM, IgA and IgG classes to the common O serotypes of P. mirabilis and the antigens to which they reacted were determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: analysis of urine from 76 patients with RA and 48 age- and gender-matched healthy controls showed that only two (4%) of the control urines but 25 (33%) of those from the RA patients were infected. The commonest infecting organism in the RA patients' urine was Proteus mirabilis which occurred twice as frequently as Escherichia coli. Proteus mirabilis was found in 52% of the infected urines of the RA patients and was always detected as a pure growth and usually in insignificant (< 10(4)/ml) numbers. It is highly improbable that this finding was the outcome of differences in age, physical ability or medication between the RA and control patient groups. Comparison of antibody levels to P. mirabilis by ELISA showed RA patients had raised (P < 0.0001, P = 0.001, P = 0.0063) levels of IgA, IgG and IgM respectively in their sera and raised (P < 0.0001, P < 0.0001, P = 0.0001) levels of IgG, IgM and IgA respectively in their urine compared with the control group. It was not possible to detect an antibody reacting to a P. mirabilis antigen that was specific to the RA patients. CONCLUSION: the results confirm that RA patients have raised levels of antibody to P. mirabilis not only in blood but also in urine and suggest that this arises because RA patients have an asymptomatic, non-significant P. mirabilis bacteriuria more frequently or more prolonged than control patients. This may be the trigger for their RA condition.

Treatment of vasculitic leg ulcers in connective tissue disease with iloprost.

Leg ulcers are a recognised manifestation of cutaneous vasculitis in connective tissue diseases (CTDs) including rheumatoid arthritis (RA). Iloprost a stable prostacyclin analogue has been successfully used to treat Raynaud's phenomenon and digital ulcers associated with CTD's. Our aim was to assess iloprost in the treatment of vasculitic leg ulcers in CTD. In this paper we describe eight cases of vasculitic leg ulceration in association with RA and CTD, treated with intravenous iloprost. The iloprost was administered for 6-8 hours daily and continued for 21-28 days. Immunosuppressive therapy was required in three patients with severe necrotising vasculitis (RAnv). Complete ulcer healing was achieved in four patients within 6 weeks of commencing therapy while rapid improvement occurred in the other four patients. This suggests that iloprost may be useful as an adjunct to therapy for vasculitic leg ulcers. A double-blind placebo controlled study of iloprost therapy for RA leg ulcers is under way.

Initial experience with endoscopic retrograde cholangiopancreatography: the role in clinical practice.

A series of 62 patients referred for endoscopic retrograde cholangiopancreatography is reported. The pancreatic or biliary ductular systems were demonstrated in 42, the success rate of cannulation improving with experience. The technique was diagnostic in 25 of 31 patients referred with hepatobiliary problems and in 3 of 11 with suspected pancreatic pathology. In a further seven patients in this latter group the examination was helpful in management. Duodenoscopy, without duct cannulation, demonstrated carcinoma of the periampullary region in two patients. Pancreatitis occurred in two patients and cholangitis in one. There are few contra-indications to the examination which should be undertaken early in the investigation of patients with cholestasis.

The treatment of hypertension with verapamil.

In a randomised double blind cross over trial, verapamil produced significant dose dependent reductions in blood pressure in 23 patients. There were minimal side-effects. All patients had some contraindication to the use of beta blocker therapy, and the role of verapmil in this situation is discussed.

Dry bones: a paleopathological study of skeletal remains from a medieval graveyard in Dundee.

We report a study on human skeletal remains excavated from a medieval city centre graveyard. The remains of approximately 75 individuals were examined and radiographs were made of selected specimens. Many bones were normal and apparently from strong, young adults. The most frequent abnormality was osteoarthritis but we also noted osteoporosis, periostitis and an example of probable Paget's disease. From measurements of long bones and using appropriate formulae, we estimated stature. The average height for males was calculated to be 172cm (5' 7") and for females 157 cm (5' 2").

Astrocytoma presenting with vasculitis.

A cerebral astrocytoma which had remained quiescent possibly for 12 years, presented with blackout, vasculitis and a lupus-like (L-E like) syndrome. The association between tumours and "L-E like" syndromes is reviewed briefly.

Developments in rheumatology consultant manpower provision: the BSR/arc Workforce Register 2003-05.

OBJECTIVES: To summarize the changes and continuing inequalities in rheumatology service provision in the UK between 2001 and 2005. METHODS: Questionnaires about demographics and workload were sent to all consultants on the BSR/arc Workforce Register in January 2003 and 2005. RESULTS: A total of 94% of 506 consultants responded in 2003 and 89% of 542 in 2005. About 19% of the consultants practice rheumatology with acute medicine. Levels of optimal provision exceed 60% in England and Wales, but are below 50% in Scotland and Northern Ireland. The levels of provision in London are substantially higher than anywhere else. The median number of hours worked per week has increased from 35.2 in 2003 to 41 in 2005. CONCLUSIONS: Rheumatology continues to expand. There is inequality with better provision in England (especially London) and Wales than Scotland and Northern Ireland. Patterns of nurse and Senior House Officer (SHO) provision correlate with consultant numbers. Thus, the catalyst for improved service is consultant expansion.

Deep venous thrombosis after total hip arthroplasty: a prospective controlled study to determine the prophylactic effect of graded pressure stockings.

Graded pressure stockings significantly reduced the incidence of venographically determined deep venous thrombosis (DVT) after total hip arthroplasty. Seventy-six patients were studied; the incidence of DVT was 54 per cent in 41 control patients and 20 per cent in 35 patients who wore stockings. Administration of blood during the operation and in the first 24 h after operation, if given in excess of blood loss, was associated with a significantly increased risk of developing DVT. The application of graded pressure stockings and the avoidance of unnecessary perioperative blood transfusion are worth while in the management of total hip arthroplasty.

Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis--a double-blind placebo controlled study.

Maxepa contains eicosapentaenoic acid (EPA) (171 mg/capsule) and docosahexaenoic acid (DHA) (114 mg/capsule). EPA acts as an alternative substrate to arachidonate, leading to the formation of the less proinflammatory prostaglandins ('3' series) and leukotrienes ('5' series). If Maxepa has anti-inflammatory properties it could be expected to reduce the requirement for NSAIDs in patients with RA. This has not been investigated nor has Maxepa therapy been studied over a full 1-yr period. Sixty-four patients with stable RA requiring NSAID therapy only were studied. Patients received either 10 Maxepa or air-filled placebo capsules per day for 12 months. All then received placebo capsules for a further 3 months. Patients were reviewed at 3-monthly intervals. NSAID requirement at entry visit for each patient was assigned as 100%. Patients were instructed to slowly reduce their NSAID dosage providing there was no worsening of their symptoms. Clinical and laboratory parameters of RA activity were also measured. There was a significant reduction in NSAID usage in patients on Maxepa when compared with placebo from month 3 [mean (95% C.I. for mean) requirement--71.1 (55.9-86.2)% and 89.7 (73.7-105.7)%, respectively]. This effect reached its maximum at month 12 [40.6 (24.5-56.6)% and 84.1 (62.7-105.5)%, respectively] and persisted to month 15 [44.7 (27.6-61.8)% and 85.8 (60.5-111.1)%, respectively] (P < 0.001, ANOVA). These patients were able to reduce their NSAID requirement without experiencing any deterioration in the clinical and laboratory parameters of RA activity.

Case report: periosteal new bone formation in Takayasu arteritis.

Periosteal new bone formation is recognized as a rare feature of arteritis but has not previously been described in association with Takayasu arteritis. We report the first case of Takayasu arteritis complicated by multifocal periosteal new bone formation of both clavicles and one scapula.

Sulphasalazine-induced lupus in psoriatic arthritis.

Lupus syndromes have been described in rheumatoid arthritis and inflammatory bowel diseases treated with sulphasalazine. We describe two cases of lupus with clinical and serological disease, developing in seronegative, immunologically nude psoriatic arthritis following sulphasalazine treatment. On cessation of sulphasalazine the clinical and serologic features of lupus disappeared. This suggests that the lupus syndrome was induced by sulphasalazine rather than unmasked by it.

Systemic lupus erythematosus: two patients treated with danazol.

Two women with systemic lupus erythematosus who showed premenstrual flaring of the disease were treated with danazol, which resulted in clinical improvement.This form of treatment needs to be assessed more widely, as there is little reported evidence that hormonal regulation has therapeutic value in systemic lupus erythematosus.

An unusual cause of arthritis.

We present a case of leprosy, an uncommon infection in the United Kingdom, which mimicked features of widely known rheumatic diseases and resulted in subsequent delay of diagnosis.

Verapamil in the management of hypertensive patients.

The hypotensive action of verapamil given orally was assessed in the outpatient management of patients with raised blood pressure, in a single blind study. Twenty-six hypertensive patients on no therapy, 14 on beta blockers and eight on methyldopa were more satisfactorily controlled when verapamil was substituted for the initial drug. There was a marked reduction in the number of side-effects, and the drug was given in many situations where beta blockade was contra-indicated.

Sex hormones in male patients with systemic lupus erythematosus: a comparison with other disease groups.

There is substantial evidence for alteration of oestrogen metabolism in both males and females with systemic lupus erythematosus (SLE). Low testosterone levels have been described in men with SLE, and it has been suggested that this may be a further predisposing factor to the development of the disease. Serum testosterone, oestradiol, FSH and LH levels were measured on two or more occasions in nine male patients with SLE. Similar estimations were performed on four other groups for comparison: ten male patients with rheumatoid arthritis, six male patients on long-term steroid therapy, eleven male patients with renal failure on long-term haemodialysis and eleven healthy male volunteers. Mean testosterone levels were significantly reduced in all disease groups and there was no significant difference between patients with SLE and those with other chronic disorders. Oestradiol levels were normal in all groups, but there was a trend to elevated mean levels of FSH and LH (p 0.05 for the haemodialysis group). Our results confirm that testosterone levels are low in males with SLE, but suggest that this is an effect of chronic disease, and therefore unlikely to be a pre-existing risk factor for the development of SLE in men.