Prevalence of genetic haemochromatosis and iron overload in patients attending rheumatology and joint replacement clinics.

BACKGROUND & AIMS: Genetic Haemochromatosis (GH) is common in North European and Celtic populations and is associated with arthropathy. We aimed to measure the frequency of the common GH mutations (C282Y and H63D), the carrier frequency of C282Y and markers of iron overload in patients who were referred to our rheumatology and joint replacement clinics. METHODS: Unselected patients attending these clinics were anonymously tested for the described mutations. Transferrin saturation and serum ferritin were also measured and if elevated, the patients had predictive counselling then named GH mutation testing. The carrier and mutation frequencies were also determined in 340 local controls. RESULTS: One hundred and sixty-one unselected patients attending these clinics were studied. The C282Y mutation carrier frequency was 1 in 5.2 in patients compared with 1 in 8.1 in controls (p < 0.005). The overall mutation frequencies were similar in patients and controls. One patient was found to be a homozygous for the C282Y mutation and eight were compound heterozygotes. Seven other patients had a raised ferritin, one of whom was a C282Y heterozygote. CONCLUSION: The C282Y carrier frequency is significantly higher in patients attending rheumatology and joint replacement clinics than in controls. Screening of these patients for GH should be considered.

Electroencephalographic tolerance and abstinence phenomena during repeated alcohol ingestion by nonalcoholics.

Certain measures of the auditory average evoked response are sensitive to alcohol and provide evidence for abstinence and tolerance during and after 10 days of alcohol consumption by nonalcoholics. Electroencephalographic techniques provide a single sensitive measure for the study of the etiology of tolerance and abstinence with particular reference to a new area of investigation with nonaddicted humans.

Audit of literacy of medical patients in north Glasgow.

AIMS: We aimed to assess the scale of the problem of illiteracy among our hospital's general medical in-patients and investigate any influence on literacy from gender, age, socioeconomic status, disease process and number of prescribed medications. METHODS: We employed a shortened version of the previously validated Rapid Estimate of Adult Literacy in Medicine (REALM) tool with medical in-patients at Glasgow Royal Infirmary. We also recorded gender, date of birth and clinical problem. Socioeconomic status was estimated from the patient's postcode using the Scottish Index of Multiple Deprivation (SIMD). RESULTS: 60 patients were invited to participate, however six (10%) declined. We therefore gathered data for 54 patients (54% male) with a mean age of 67 years. The female group had a significantly higher mean age of 73 years versus 62 years in men. The mean SIMD quintile was 3.5 (1 least deprived, 5 most deprived) and the mean number of medications was 7.55% of our patients had a mean score of < 60 which represents low health literacy. There were no significant differences in literacy between men (median score 59) and women (median score 60). Reading ability was not found to be associated with socioeconomic group, diseased body system or number of medications on the drug chart (data not shown). CONCLUSIONS: Low level health literacy is prevalent. Affected individuals may have difficulty understanding patient-orientated health literature, medication instructions, clinic appointment cards and hospital signage.

Changes in glutathione in intact erythrocytes during incubation with penicillamine as detected by 1H spin-echo NMR spectroscopy.

1H spin-echo NMR spectroscopy was used to study changes in glutathione status in intact erythrocytes. The concentration of glutathione in suspensions of erythrocytes in 2H2O saline is significantly different in cells from patients with rheumatoid arthritis than in controls from normal healthy volunteers. It is observed that the methods of separation and suspension affect lactate metabolism in red cells. Incubation of erythrocytes with solutions of the therapeutic agent D-penicillamine in 2H2O saline produced a change in glutathione resonances which is indicative of an increase in diglutathione concentration. Signals from the methyl groups of penicillamine decreased at a commensurate rate. Incubation of normal cells with plasma from patients with rheumatoid arthritis who had the same blood group as the normal volunteer indicated a much larger fall in glutathione signal with plasma from a patient treated with penicillamine than from a patient on non-steroidal anti-inflammatories.

Neuropathies in the rheumatoid patient: a case of the heavy hand.

Rheumatoid Arthritis (RA) is a common inflammatory arthritis' with pain and loss of function among its most disabling symptoms. These are mostly secondary to inflammation or mechanical damage to the joints. However it is also important to consider disease complications as a cause of symptoms, especially when the response to treatment is suboptimal. We report an RA patient whose symptoms were resistant to standard therapy, and were actually due to peripheral neuropathy.

Successful treatment of Raynaud's Syndrome with prostacyclin.

There is evidence to suggest that platelet activation occurs in Raynaud's syndrome. We evaluated the effect of prostacyclin (PGI2) a potent antiplatelet and vasodilator agent in 5 female patients with Raynaud's syndrome. Outpatient visits were made at weekly intervals for 4 weeks. At the first visit buffer solution (Wellcome Laboratories) was infused intravenously for 5 hrs, thereafter three five hr infusions of PGI2 at a peak dose of 10 ng/Kg/min were given. Six weeks after the infusions patients were reviewed. Symptomatic improvement, including healing of ischaemic ulcers, occurred in 4 out of 5 patients. Thermography confirmed an increase in hand temperature after PCI2. Subjective and objective improvement has persisted for at least 6 weeks after the last treatment.

Variables affecting efficacy and toxicity of sulphasalazine in rheumatoid arthritis. A review.

Studies of sulphasalazine in rheumatoid arthritis have used largely empirical doses. The available literature suggests that the optimum dose appears to be greater than 40 mg/kg/day. Despite the relationship between dose and efficacy and a good correlation between dose and serum concentrations of sulphasalazine and its metabolites, no relationship has been demonstrated between efficacy and serum concentrations of sulphasalazine or its metabolites, although there is some suggestion that higher concentrations on single dosing are achieved in patients who develop upper gastrointestinal symptoms. Furthermore, acetylator phenotype does not affect efficacy, although upper gastrointestinal symptoms are more common in slow acetylators.

Comparison of white blood cell dyscrasias during sulphasalazine therapy of rheumatoid arthritis and inflammatory bowel disease.

A total of 7 out of 158 rheumatoid arthritis patients followed for 6 months have developed leucopenia during sulphasalazine therapy at our centre. Two of these patients developed profound leucopenia which necessitated admission to a laminar flow unit, and case reports of these are documented in detail. These results are compared with those from other centres in the United Kingdom where patients with rheumatoid arthritis have been treated, and also with experience gained from patients with inflammatory bowel disease who have been treated with sulphasalazine.

Short report: the effect of misoprostol on the anaemia of NSAID enteropathy.

BACKGROUND: Small bowel ulceration is an increasingly recognised complication of therapy with non-steroidal anti-inflammatory drugs (NSAID). The ulceration is a potent site of blood loss contributing to unexplained iron deficiency anaemia in patients with arthritis. No drug is currently available to treat NSAID small bowel ulcers. METHODS: We have retrospectively examined the effect of therapy with the prostaglandin E1 analogue misoprostol on the anaemia of patients with enteroscopically proven NSAID small bowel enteropathy. RESULTS: All of the patients had proven iron deficiency anaemia. Eleven patients received misoprostol and ten received no treatment. Haemoglobin in the misoprostol-treated group rose significantly from median (range) 9.1 (6.2-10.6) g/dL (95% confidence intervals 8.76, 10.13) to 10.6 (6.5-16.8) g/dL (95% confidence intervals 10.06, 11.82); P = 0.004). Those patients who did not receive misoprostol had no significant change in their haemoglobin: 9.1 (7.5-10.6) g/dL to 8.1 (5.6-14.7) g/dL (P = N.S.). CONCLUSION: Misoprostol therapy was associated with an improvement in the anaemia in patients with proven NSAID enteropathy.

Comparison of azapropazone and naproxen in rheumatoid arthritis.

A double-blind crossover trial was carried out in 15 patients with definite rheumatoid arthritis to compare the effectiveness of 1200 mg azapropazone daily and 750 mg naproxen daily, each drug being given for 2 weeks. Patients also received placebo therapy before and between the two treatment periods. The results of subjective and objective assessments showed that both drugs were significantly superior to placebo, but no significant difference could be demonstrated between the two drugs.

Clinical therapeutic trial of aspirin and azapropazone in rheumatoid arthritis when prescribed singly and in combination.

A double-blind, crossover trial was carried out to assess the clinical efficacy of 3.6 g aspirin, 1200 mg azapropazone and the two drugs together in 24 adult patients with classical or definite rheumatoid disease. Pain score, morning stiffness and patients' assessment of pain were significantly improved for each drug regimen when compared to placebo. There was no significant difference among the individual drug regimens. Azapropazone was the best drug regimen in terms of improving pain score, morning stiffness and patient assessment of pain, but this was not statistically significant. It is concluded that there is no justification for prescribing aspirin with azapropazone in patients with rheumatoid disease.

The use of serum ferritin estimation in the investigation of anaemia in patients with rheumatoid arthritis.

We report a retrospective study of 101 patients with rheumatoid arthritis and anaemia undergoing investigation in a teaching hospital rheumatology unit. Patients with anaemia of chronic disorder had significantly higher serum ferritin (p < 0.0001), mean corpuscular volume (p < 0.05), and acute phase reactants (p < 0.001). The sensitivity, predictive value and validity of measuring serum ferritin to predict the absence of bone marrow iron stores was studied. Maximum validity (89%) was achieved by defining iron deficiency as occurring when serum ferritin was < 75 ng/ml. 93% of patients with ferritin < 50 ng/ml were iron deficient on bone marrow examination. 91% of patients with ferritin > 100 ng/ml were iron replete on bone marrow examination. 86% of patients had ferritin < 50 or > 100 ng/ml. Age was not a significant confounding factor. Serum ferritin concentration is an informative investigation in rheumatoid patients with anaemia. Correct interpretation of the results eliminates the need for bone marrow aspiration in the majority of cases.

The treatment of juvenile arthritis.

Until recently, two different classification systems for juvenile arthritis (JA) were utilised, each with its own terminology and subclassification. It has been recognised that particularly within the polyarticular and pauciarticular groups, many distinct subsets exist each with a different prognosis. As a result, a new classification system for JA has been developed. It is hoped that this will allow more accurate assessment of incidence and aetiology of the various subtypes in future generations and in time will allow therapy to be targeted at those most likely to achieve benefit. Since there is a new classification system for JA, the vast majority of published clinical studies were performed using the old classification system. For the purposes of this review, unless otherwise stated, the American College of Rheumatology classification will be used. This is outlined in Table 1 with clinical features of the major subtypes described in Table 3. This review will cover current best practice and discuss future directions for research using the recent advances in the treatment of rheumatoid arthritis (RA) as a model.

The geometric knee replacement in polyarthritis.

The British Orthopaedic Association assessment questionnaire for knee replacements was adapted to allow comparison of the severity of underlying polyarthritis with the benefits of geometric knee replacement in a retrospective study of 150 knees between six months and six years after operation. Total or partial relief of pain was achieved in 81 per cent of the operation, and changes in mobility occurred in fewer patients. Late sepsis remained a serious complication of nine per cent of the operations and one patient died from septicaemia. Late sepsis was associated with previous synovectomy or osteotomy. Retropatellar pain rarely interfered with the mobility of the patient. There was no association of operations that failed with a high erythrocyte sedimentation rate, a high platelet count, a low haemoglobin level or with a strongly positive rheumatoid factor but pain in the contralateral knee was associated with a diminished functional capacity.

Oral gold: a comparison with placebo and with intramuscular sodium aurothiomalate.

The therapeutic and toxic effects of the orally absorbed gold compound auranofin have been compared with placebo and parenterally administered sodium aurothiomalate (GST) in 90 patients with active rheumatoid arthritis over one year. At the end of this period 57% of patients on auranofin, 73% on GST and 0% on placebo remained on therapy. Toxicity caused discontinuation of therapy in 10% of patients on auranofin, 20% on GST and 7% on placebo. Lack of response to therapy led to withdrawal of 20% on auranofin, 0% on GST and 90% on placebo. Multiple clinical and biochemical assessments were performed during this study. Analysing them separately, and in the case of 6 of them grouped together in a disease activity index, the same trend is apparent throughout, namely that placebo has no effect on active inflammatory rheumatoid arthritis, and that both gold drugs are beneficial. GST has an earlier effect and tends to produce a greater change but after one year there was no significant difference between the 2 gold drugs for any parameter assessed. Gold levels in plasma or erythrocytes did not predict or correlate with either the development of toxicity or clinical efficacy. This study has demonstrated the second-line potential of auranofin which seems to be effective at gold concentrations in the blood below those observed with GST therapy. Toxicity limits the use of gold salts in RA. If the reduced incidence of adverse reaction with auranofin observed in this study is substantiated in larger numbers over prolonged periods, the use of gold at an earlier stage of disease may be facilitated.

Second line therapy in rheumatoid arthritis--a four year prospective study.

One hundred and twenty-three rheumatoid patients were commenced on one of the three second-line agents: sodium aurothiomalate (GST), penicillamine (P), or levamisole (L). After four years, 39% of the GST group, 20% of the penicillamine group, and 8% of the levamisole group remained on the original agent. Fifty five % of patients, however, were receiving some second-line agent at four years, and patients showed an improvement in inflammatory indices irrespective of whether or not they were still receiving second-line therapy. It is unclear whether this improvement reflects the natural history of the disease, or the fact that regular clinic attendance identifies patients who require further second-line therapy following cessation of the initial agent.

A survey of renal function in outpatients with rheumatoid arthritis.

The acute renal side-effects of nonsteroidal anti-inflammatory drugs are well documented. These include interstitial nephritis, hyperkalaemia, renal tubular acidosis, fluid retention, hypertension and nephrotic syndrome. The long-term effects are less well known. We have carried out a cross-sectional survey of an unselected out-patient population with definite or classical rheumatoid arthritis to determine the prevalence of renal problems in this group. Thirty-four patients (20%) were shown to have an abnormality as defined by our criteria but in the majority this was transient or had been previously recognised. Thirteen patients (8%) had a persistent unexplained abnormality but only 1 had merited renal biopsy using established criteria (Patient 1). We conclude that the long-term use of NSAID's is associated with relatively few renal side-effects.

The spectrum of disease associated with a positive ANCA.

This is a retrospective analysis of all patients with a raised titre of ANCA in a single centre over a two-year period. Sixty-five patients were identified and clinical data is presented for 58 of these-34 male and 24 female. The median age is 56 years (13-83). Fourteen patients had Wegener's granulomatosis, 14 microscopic polyarteritis nodosa and 30 had other diagnoses. The patients with unexpectedly positive results are discussed in detail. This study confirms the sensitivity of ANCA in Wegener's granulomatosis and microscopic polyarteritis nodosa but suggests that the test is not as specific as initially claimed.

Does hypothyroidism predispose to gold-induced thrombocytopenia?

Two patients receiving gold therapy for rheumatoid arthritis suffered from a sudden and unpredictable fall of platelet count. Spontaneous bleeding into the soft tissues occurred in both cases, and nasal epistaxis or macroscopic haematuria complicated each case. Both patients were on long term replacement therapy with thyroxine and it is postulated that changes associated with hypothyroidism may predispose to acute thrombocytopenia due to gold. Patients who suffer from hypothyroidism may require particularly close monitoring whilst on gold therapy.

Spontaneous fractured neck of femur in rheumatoid arthritis: absence of radiographic changes on initial X-ray.

Spontaneous fractures have been documented in patients with osteoporosis and have been described in patients with rheumatoid arthritis. Two patients with rheumatoid arthritis who sustained femoral neck fractures in the absence of trauma are documented. Despite severe pain initial radiograph failed to demonstrate evidence of fracture, but subsequent radiographs later showed fractures in both cases. It is important in rheumatoid patients with continuing severe hip pain of sudden onset to suspect a stress fracture even if initial radiographs are normal.