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Biomedical subjects

H A Bird

Publications and source records attributed to H A Bird.

At least 19 recordsLinked to original sources

A pharmacokinetic and tolerance study of romazarit in patients with rheumatoid arthritis.

Romazarit is a new drug for which animal pharmacology suggests a disease-modifying action in rheumatoid arthritis (RA). These animal studies predict that plasma romazarit concentrations within the range 50-100 mg l-1 may be required for efficacy in the clinic. Therefore, a pharmacokinetic study was designed to estimate the dosage required to achieve these concentrations in man. Twenty-four patients with RA entered a double-blind controlled assessment receiving either placebo, 100 mg t.i.d., 350 mg b.i.d., or 350 mg t.i.d., for 6 days. Pharmacokinetic profiles were measured after single doses and after the last of the multiple doses. Adverse events were mainly trival and were distributed almost equally between all three treatment and the placebo groups. Plasma romazarit concentrations were not dose-proportional after the single doses. Mean peak plasma drug concentrations were 11.8, 66.7, and 159 mg l-1 at steady state after 100 mg t.i.d., 350 mg b.i.d., and 350 mg t.i.d. The mean urinary recovery of drug-related material (mostly ester glucuronides) was 71 per cent of the dose during the dosage interval. The renal clearance of romazarit glucuronides correlated with creatinine clearance (p less than 0.01). Saturable tubular secretion of glucuronides coupled with reversible glucuronidation would explain these findings. It is predicted that oral doses of 450 mg romazarit given 12-hourly will result in plasma concentrations within the target range of 50-100 mg l-1.

Administration, Oral

The effect of non-steroidal anti-inflammatory drugs on faecal flora and bacterial antibody levels in rheumatoid arthritis.

The faecal flora and bacterial antibody levels of 22 patients with active rheumatoid arthritis (RA) were compared with those of 26 patients with osteoarthritis (OA) undergoing comparable treatment with non-steroidal anti-inflammatory drugs (NSAIDs), and a further 22 patients with OA who were not receiving NSAIDs. Faecal counts of Clostridium perfringens were significantly higher in the RA patient group and in those OA patients receiving NSAIDs, compared with those OA patients not taking NSAIDs (P = 0.032, P = 0.0004 respectively). Total aerobic and anaerobic counts were, however, identical in all three groups. Levels of serum IgA antibody to the alpha toxin of Cl. perfringens were higher in the RA group and in the OA group taking NSAIDs than in OA patients not taking NSAIDs (P = 0.011, P = 0.055). Serum IgG antibody to alpha toxin was higher in the RA group than in OA patients both on and off NSAIDs (P = 0.019, P = 0.0072) and also a group of normal controls (P = 0.032). These results suggest that the increased faecal counts of Cl. perfringens together with the associated increased antibody levels seen in this and previous studies are more likely to result from NSAID therapy used to treat the disease than from a disease specific change in bowel flora.

Adult

Phthalylsulphathiazole in rheumatoid arthritis.

Sixteen patients with active rheumatoid arthritis were treated with phthalylsulphathiazole (4 g/day) over a period of 24 weeks. Although there was some statistically significant improvement in plasma viscosity, IgM, pain score, morning stiffness and summated change score, this was either intermittent or not maintained. Five patients withdrew from the trial before completion, four (25%) with non-serious adverse reactions and one patient from lack of efficacy; only one patient elected to remain on the drug beyond the 24-week period. Low free and total sulphathiazole serum concentrations were found, confirming that most of the drug remained within the gut. This investigation suggests, certainly at the dose used, that phthalylsulphathiazole does not have the properties of a second-line agent. Higher doses of the drug will not be ethically feasible.

Arthritis, Rheumatoid

Survey of satisfaction with care in a rheumatology outpatient clinic.

Consumer satisfaction is increasingly recognised by hospital administrators and health care providers as an important aspect of health care. A study was undertaken to investigate the satisfaction with care among patients with rheumatoid arthritis (RA) attending a rheumatology outpatient clinic at Leeds General Infirmary. The Leeds satisfaction questionnaire was developed and rigorously tested for reliability (Cronbachs alpha) and stability (test/retest). The Leeds satisfaction questionnaire was then completed by 70 patients with RA who had attended the Leeds General Infirmary on at least three previous occasions. The results showed that patients were, in general, satisfied with the care they received. The highest satisfaction scores were obtained on the scale for technical quality and competence of health professionals. The least satisfaction was accredited to the difficulty of unscheduled access to the clinic and the lack of continuity with the providers of care. The time spent in the waiting area before consultation was highlighted as the one aspect which caused the greatest dissatisfaction.

Adult

A double blind, multicentre, placebo controlled trial of lornoxicam in patients with osteoarthritis of the hip and knee.

Lornoxicam is a new non-steroidal anti-inflammatory agent (NSAID) with a similar pharmacological profile to other oxicams and a potency 10 times greater than piroxicam. A multicentre, randomised, double blind, parallel group study was undertaken to compare the efficacy and tolerance of four weeks' treatment with lornoxicam (6 mg once daily, 4 mg twice daily, and 6 mg twice daily) and placebo in patients with osteoarthritis of the hip or knee. A dose related efficacy of lornoxicam was shown by the numbers of patients in each treatment group who withdrew from the trial owing to inadequate symptom relief (12/40 (30%) receiving placebo, 6/40 (15) receiving lornoxicam 6 mg daily, 4/40 (10%) receiving lornoxicam 8 mg daily, and none receiving lornoxicam 12 mg daily). This effect was confirmed by pain relief scores, which were significantly better than placebo during treatment with lornoxicam 8 mg and 12 mg daily, the effect of 12 mg daily being significantly superior to that of 8 mg daily. Similar results were obtained from functional status scores. Mean functional index (Lequesne) scores were significantly greater than placebo only at a daily dose of 12 mg lornoxicam. Lornoxicam was generally well tolerated, though some gastrointestinal side effects were seen as has been reported with other NSAIDs. Laboratory investigations showed no evidence of drug toxicity.

Administration, Oral

Urinary excretion of pyridinium crosslinks of collagen in patients with osteoporosis and the effects of bone fracture.

Values for the urinary excretion of pyridinium crosslinks of collagen, pyridinoline and deoxypyridinoline, in a group of 30 elderly women with femoral fractures associated with osteoporosis and a group of 20 women without recent fracture but with overt or suspected osteoporosis were compared with 27 control subjects matched for age. Relative to the control group, the excretion of the crosslinks was significantly higher in the group with fractures and the group with osteoporosis. Fractures contributed markedly to the excretion of pyridinium crosslinks as the patients with fractures showed significantly higher excretion of pyridinoline and deoxypyridinoline than the group without recent fractures. This was confirmed by the fact that excretion of pyridinium crosslinks in patients with accidental bone fractures was significantly higher than for healthy control subjects matched for age and sex. The crosslinks appear to provide valid indices of bone resorption, but the effects of bone fracture must be considered in the clinical application of this technique.

Aged

Repetitive strain disorder: towards diagnostic criteria.

Thirteen women (mean age 48.2 years; range 25-60 years) all of whom had developed musculoskeletal symptoms during employment in an industrial job with repetitive tasks were referred by their trade unions for adjudication on the cause of symptoms. One had rheumatoid arthritis. A study of the other 12 women provided an opportunity to document the natural history of repetitive strain disorder. Early symptoms of weakness were diffuse but were always relieved by rest. Several months later localisation of symptoms at a tendon, nerve, or enthesis could be predicted from the analysis of the action required in the particular repetitive task. Six of the 12 women required an operation several years later, thus providing histological confirmation of the presence of a lesion. Early loss of grip strength measured by a sphygmomanometer cuff compared with an unaffected control subject and improved by rest may be the most valuable sign in excluding compensation neurosis. The estimated prevalence of repetitive strain disorder defined by these strict criteria was at least 2% in conveyor belt workers.

Adult

The development and use of Patient Knowledge Questionnaire in rheumatoid arthritis.

A multi-choice Patient Knowledge Questionnaire (PKQ) was developed for use with patients with rheumatoid arthritis (RA). Test/re-test was used to test its stability (r = 0.81), and Kuder Richardson formula 20 (r = 0.72) for internal consistency. Seventy randomly selected RA patients then completed the PKQ in a rheumatology out-patient clinic of a large teaching hospital. There was a wide variation in total scores ranging from 3 to 28 out of 30. Total scores correlated with years of general education (P less than 0.05) but not with disease duration or age. Sixty-two per cent of patients knew that the cause of RA is, as yet, unknown but 27% thought it could be caused by injury and 11% by cold damp weather. Fifty-two per cent had no idea why they had blood tests. All but four patients were taking some form of medication but there was widespread confusion about disease-modifying drugs and non-steroidal anti-inflammatory drugs (NSAIDs). Exercise was reasonably well understood but many patients were unable to differentiate between methods of energy conservation and joint protection. This study highlights the need for careful individual knowledge assessment by use of tools such as the PKQ and effective patient education programmes.

Activities of Daily Living

Renal tubular dysfunction in rheumatic diseases.

Evidence of renal tubular dysfunction as defined by abnormal urinary levels of alpha 1 and beta 2 microglobulin with or without microalbuminuria was found in 47 (16.5%) of 285 patients with a variety of rheumatic diseases, compared with a prevalence of less than 1% in 500 healthy adults. Previous work from this unit has shown a prevalence of tubular dysfunction of 24% in patients with severe rheumatic disease admitted to hospital, probably associated with severe rheumatoid arthritis. Although our study confirms a high prevalence of renal tubular dysfunction, we have shown that it is related to age and intercurrent illness, particularly urinary tract infection, rather than to rheumatic disease or drug therapy, although it is possible drug therapy could add to a compound insult on ageing or damaged kidney.

Aged

Human nocturnal blood melatonin and liver acetylation status.

The human dark phase melatonin concentrations exhibit a wide range of values. In an attempt to explain this variation, we measured 2250-2305 h melatonin levels by radioimmune assay in eleven fast and eleven slow acetylator phenotypes. No statistical difference between the two groups existed, suggesting therefore that such variations are not due to acetylator status. The study revealed a negative relationship between body weight or area and nocturnal melatonin concentration. No correlation was found between dark phase melatonin levels and age, anxiety, depression, or sleep rating.

Acetylation

Drug interactions in arthritic patients.

The drug treatment of 100 consecutive new patients admitted to a regional rheumatology centre was reviewed. Potential drug interactions actions were sought according to appendix one of the British National Formulary (September 1989) and identified in 55 of 100 patients. The clinical and laboratory features of these patients were then reviewed, showing that only 11 displayed clinical manifestations of a drug interaction. Five patients had drug induced drowsiness, which was easily corrected, five a raised serum creatinine, which was less easily corrected, and one both. Although there is considerable potential for drug interaction in patients with severe arthritis, the proportion of patients who display clinical manifestations of this is small.

Adult

Polymyalgia rheumatica and rheumatoid arthritis of the elderly: a clinical, laboratory, and scintigraphic comparison.

Clinical, laboratory, and scintigraphic features of 16 patients with polymyalgia rheumatica and 23 patients matched for age presenting with classical or definite rheumatoid arthritis (American Rheumatism Association 1958 criteria) of the elderly were compared in order to define features that might distinguish between these two syndromes. The sensitivity of proposed diagnostic criteria for polymyalgia rheumatica was always higher in the group with polymyalgia rheumatica, though only significantly so for morning stiffness. A comparison of 27 different laboratory features showed few significant differences between the diseases, though correlation between laboratory variables within each of the disease groups differed, perhaps suggesting a fundamental pathogenetic difference between them. Scintigraphy of the shoulder joint proved of no value in differential diagnosis. It was concluded that polymyalgia rheumatica and rheumatoid arthritis of the elderly are probably discrete clinical entities. Bilateral upper arm tenderness, lack of positive rheumatoid factor, and a normal caeruloplasmin are the most valuable features for distinguishing polymyalgia rheumatica from rheumatoid arthritis of the elderly.

Aged

The arthritis impact measurement scales: an anglicized version to assess the outcome of British patients with rheumatoid arthritis.

The Arthritis Impact Measurement Scales (AIMS) is an American questionnaire designed to measure the health status of patients with arthritis. Its suitability for use with British patients with rheumatoid arthritis (RA) has been tested. A study on 30 patients high-lighted the need to anglicize the terminology and spelling. A further 30 patients found the modified questionnaire easier to complete than the original. The concurrent validity of this modified AIMS was then tested on 59 patients by comparison with two widely accepted standards. Physical function and pain scales were tested against the Stanford Health Assessment Questionnaire (HAQ). Because the HAQ has no psychological component, psychological status was compared with the Hospital Anxiety and Depression Scale (HAD). Results showed a good correlation between the scales and it is concluded that the modified version of the AIMS may be used with confidence in British patients with RA.

Adult

Failure of selenium-ace to improve osteoarthritis.

Selenium-ACE, a formulation containing the trace element selenium with three vitamins, is widely promoted for the treatment of arthritis. A controlled double-blind trial of Selenium-ACE in osteoarthritis failed to demonstrate any significant efficacy for the compound over placebo at 3 or 6 months though there was a non-significant trend to improvement in some clinical parameters in both groups. Side-effects were more frequently seen in the placebo group.

Adult

A multicentre double-blind comparison of auranofin, intramuscular gold thiomalate and placebo in patients with psoriatic arthritis.

The efficacy and safety of the oral gold compound auranofin and intramuscular gold thiomalate have been compared in a placebo-controlled, double-blind, four-centre trial in 82 patients with psoriatic arthritis requiring remittive drug therapy. There were statistically significant falls in Ritchie articular index, visual analogue pain score and ESR at 12 and 24 weeks following i.m. gold but no significant changes in the auranofin group. Intramuscular gold was safe and more effective than auranofin as a second-line, suppressive antirheumatic agent for patients with psoriatic arthritis when followed for 6 months.

Adult

Methylsulphasalazine in rheumatoid arthritis.

Methylsulphasalazine, which differs from sulphasalazine by the addition of one methyl group, may provide the benefits of the parent drug with fewer side-effects in rheumatoid arthritis (RA). We describe the outcome of its use in RA. Of 21 patients entered into the study, 10 successfully completed 6 months of therapy; five developed adverse effects, four withdrew for reasons unrelated to drug treatment and two stopped because of inefficacy. No serious adverse effects were reported. A statistically significant improvement in most clinical assessments was observed from weeks 8-12 onwards. Significant improvement in plasma viscosity was observed and there was a trend towards improvement in serum CRP, histidine and IgM concentrations. There was a good correlation between mean serial changes in clinical and biochemical assessments indicating that the drug may exhibit the properties of a second-line agent. Median steady-state serum concentrations of methylsulphasalazine and methylsulphapyridine were 26.6 micrograms/ml and 2.85 micrograms/ml respectively.

Adult