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Biomedical subjects

H A Bird

Publications and source records attributed to H A Bird.

At least 37 records · Page 2Linked to original sources
PubMed1996

An open study to assess the safety and tolerability of meloxicam 15 mg in subjects with rheumatic disease and mild renal impairment.

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which has shown potent anti-inflammatory properties but good gastrointestinal (GI) renal tolerability. The safety and tolerability profile of orally administered meloxicam 15 mg given once daily over a 28 day treatment period in renally impaired patients with rheumatic disease is presented here. A total of 25 patients (aged 43-78 yr, mean age 70 yr) with rheumatic disease and mild renal impairment were enrolled in this multicentre, open-label study, with 22 patients completing the 28 day treatment period. The median estimated creatinine clearance and N-acetyl-beta-glucosaminidase/creatinine ratios (a marker of renal tubular damage) recorded at day 14, day 28 or 4-7 days after meloxicam treatment was terminated, were not statistically significantly different from baseline values. There was no evidence of accumulation of meloxicam. Overall, meloxicam was well tolerated. The most common adverse events were GI complaints of abdominal pain and dyspepsia. No adverse events related to the urinary system, or increases in serum urea or potassium were recorded. The results suggest that meloxicam, 15 mg once daily, does not further compromise renal function or result in accumulation of meloxicam over this treatment period in patients with pre-existing mild renal impairment.

Adult↗
PubMed1996

Relationship between genotype for the cytochrome P450 CYP2D6 and susceptibility to ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVES: To determine whether particular genotypes for the cytochrome P450 enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to ankylosing spondylitis (AS) and rheumatoid arthritis (RA), or linked with any specific clinical or familial features of the two conditions. METHODS: CYP2D6 genotypes were determined in 54 patients with AS, 53 patients with RA, and 662 healthy controls. Leucocyte DNA was analysed for the presence of mutations by restriction fragment length polymorphism analysis with the restriction enzyme Xbal and by two separate polymerase chain reaction assays. RESULTS: On the basis of odds ratio (OR), individuals with two inactive CYP2D6 alleles were more susceptible to AS than controls (OR 2.71, 95% confidence interval (CI) 1.04 to 7.08), with a stronger effect for the CYP2D6B allele (OR 4.11, 95% CI 1.54 to 11.0). No significant differences in the distribution of overall genotypes and allele frequencies were observed between RA and controls. No significant relationships were found between the skeletal, extraskeletal or familial features of AS or RA (iritis, psoriasis, inflammatory enteropathy and rheumatoid nodules, kerato-conjunctivitis sicca, pleuritis, rheumatoid and antinuclear factors) and the overall genotype. CONCLUSIONS: Our findings suggest a modest association between homozygosity for inactive CYP2D6 alleles, particularly CYP2D6B alleles, and susceptibility to AS. However, our results fail to demonstrate a genetic link between CYP2D6 genotype and RA.

Aged↗
PubMed1996

Urinary glucaric acid excretion in rheumatoid arthritis: influence of disease activity and disease modifying drugs.

OBJECTIVE: To examine if a correlation exists between cytochrome P-450 enzyme induction and disease activity in patients with rheumatoid arthritis (RA), measuring urinary excretion of D-glucaric acid (GA) as an index of phase II drug metabolism. METHODS: Patients with RA were treated with sulphasalazine, sodium aurothiomalate, or D-penicillamine in standard dose regimens, for 24 weeks. Patients with ankylosing spondylitis (AS) or non-inflammatory arthritis (NIA) acted as controls. The urinary GA:creatinine ratio was measured at 0, 12, and 24 weeks of treatment. RESULTS: Patients with RA had a slightly greater urinary GA:creatinine ratio than patients with AS or NIA at baseline; this increased during treatment with disease modifying antirheumatic drugs (DMARDs). Sulphasalazine treatment had a greater effect on GA excretion than sodium aurothiomalate or D-penicillamine; this difference was statistically significant between weeks 0 and 12 (p = 0.01). Gamma glutamyltranspeptidase concentration showed a weak correlation with GA excretion between weeks 0 and 12 (p = 0.03), but all other measurements of changes in disease activity (plasma viscosity, C reactive protein, platelets, and articular index) were found not to correlate with GA excretion between weeks 0-12 or 0-24. CONCLUSION: The increased excretion of GA in patients with RA receiving DMARD treatment is probably the result of an indirect effect on hepatic metabolism bearing no relationship to disease activity.

Adult↗
PubMed1996

Bone alkaline phosphatase in rheumatoid arthritis: a longitudinal study.

OBJECTIVE: To determine whether the raised total alkaline phosphatase (TAP) found in patients with active rheumatoid arthritis (RA) is derived primarily from an increase of the bone or liver isoenzyme, and to evaluate the treatment effect of steroids and disease modifying antirheumatic drugs (DMARD) on bone alkaline phosphatase (BAP) in serial analyses. METHODS: 58 patients with RA were treated with the DMARD gold sodium thiomalate (n = 22), D-penicillamine (n = 18), or sulfasalazine (n = 18) over a 24 week period with regular assessment of disease activity and measurement of BAP using a newly developed specific double monoclonal radioimmunometric assay. RESULTS: In the RA group as a whole, BAP correlated with TAP at all time points (e.g., Week 0 rs = 0.50, p < 0.0001). In contrast, no correlation was found between the intraindividual change of BAP and TAP between Weeks 4 and 24. TAP was correlated with disease activity (assessed by plasma viscosity rs = 0.33, p < 0.02 for the whole RA group and rs = 0.48, p < 0.0002 for intraindividual change from Weeks 4 to 24). Similarly, gamma-glutamyltranspeptidase was correlated with disease activity (rs = 0.56, p < 0.0001, and rs = 0.50, p < 0.0001, respectively). In contrast, BAP was not correlated with disease activity. Low dose steroids and the 3 DMARD studied had no significant effect on the time course of BAP. CONCLUSION: In the majority of patients with active RA, any increase of TAP is not mirrored by an increase of BAP. This supports the hypothesis that inflammatory reactions result in an increase in the plasma concentration of the membrane bound enzymes of the hepatobiliary system, including gamma-glutamyltranspeptidase and the liver isoenzyme of alkaline phosphatase, which is likely to be responsible, at least in part, for the increase of TAP. Since BAP is not correlated with disease activity, BAP measurements are not useful in monitoring response to treatment.

Aged↗
PubMed1995

Polymorphic acetylation: lack of influence of rheumatic disease activity and concomitant drug administration.

Acetylation polymorphisms have been linked with a tendency to develop rheumatic diseases. We investigated the effect of changes in the disease activity of patients with rheumatoid arthritis (RA) during disease-modifying antirheumatic drug (DMARD) treatment, and on the capacity of these patients to acetylate the sulphonamide sulphadimidine. Fifty-four patients with RA treated with gold, sulphasalazine or D-penicillamine, 12 patients with AS and 16 patients with non-inflammatory arthritis (NI) were investigated over a 24-week period. The capacity of these individuals to acetylate sulphadimidine was determined at baseline and after 12 and 24 weeks. Although there was a tendency for sulphadimidine acetylation to increase in patients with RA from a median of 84.5% [interquartile range (IQR) 77.0-95.0%] at baseline to 90.5% (IQR 77.5-96.0%) at week 24, this failed to reach statistical significance. In contrast, the trend in patients with AS or NI was towards a decrease in acetylation. There was no correlation between changes in disease activity and sulphadimidine acetylation during DMARD intervention.

Acetylation↗
PubMed1994

A clinical and biochemical assessment of methotrexate in rheumatoid arthritis.

Low-dose methotrexate has gained widespread acceptance as a second-line agent in rheumatoid arthritis (RA). The Leeds Human Model Screening System (LHMSS) is a validated screening mechanism allowing the rapid evaluation of compounds for their potential as anti-rheumatic agents, the results of which have been confirmed in longer term studies. We have evaluated methotrexate in patients with RA using the LHMSS at a maintenance dose of 10mg/week. Significant change occurred in four out of eleven variables over a 24-week period (p < 0.01). This degree of change is greater than that seen with nonsteroidal anti-inflammatory agents but less than with other recognised second-line agents such as D-penicillamine, suggesting that methotrexate may have less potential as a second-line agent than D-penicillamine.

Arthritis, Rheumatoid↗
PubMed1994

Urinary excretion of pyridinium crosslinks of collagen correlated with joint damage in arthritis.

The urinary excretion of the collagen crosslinking compounds pyridinoline and deoxypyridinoline have been determined in patients with morphologically different subgroups of OA and RA. There was no significant difference in pyridinoline or deoxypyridinoline excretion when patients with four grades of severity of OA were compared, although the median excretion of pyridinoline and deoxypyridinoline for the OA group as a whole was raised above values found in a healthy control population. Patients with severe or late (burnt-out) RA were found to have a significantly greater excretion of pyridinoline and deoxypyridinoline than patients with early (< 6 months duration) or mild RA.

Aged↗
PubMed1994

An evaluation of the effectiveness, safety and acceptability of a nurse practitioner in a rheumatology outpatient clinic.

Seventy patients with RA were randomly allocated to either a Rheumatology Nurse Practitioner (RNP) or Consultant Rheumatologist (CR) clinic. They were seen on six occasions in 1 year. Effectiveness and safety were assessed by biochemical, clinical, psychological and functional variables; patient knowledge and satisfaction were measured by questionnaire. At week 0 the groups were well matched clinically and demographically. By week 48 significant improvements had occurred in plasma viscosity and articular index within both groups. In patients managed by the RNP, pain, morning stiffness, psychological status, patient knowledge and satisfaction had all improved significantly (P = 0.001; P = 0.028; P = 0.0005; P < 0.0001; P < 0.0001 respectively), improvements not mirrored by the CR cohort. Between group comparisons also showed significant differences by the end of the study. Compared to the CR patients, the RNP suffered from lower levels of pain (P < 0.05), had acquired greater levels of knowledge (P < 0.0001) and were significantly more satisfied with their care (P < 0.0001).

Adult↗
PubMed1994

Phenotype/genotype relationships for the cytochrome P450 enzyme CYP2D6 in rheumatoid arthritis: influence of drug therapy and disease activity.

OBJECTIVE: To determine whether particular genotypes for the cytochrome P450 enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to rheumatoid arthritis (RA) and whether CYP2D6 enzyme activity is altered as a result of the disease or its treatment. METHODS: CYP2D6 genotypes and metabolic phenotypes were determined for 53 patients with RA and 73 healthy controls. Genotyping was carried out by restriction fragment length polymorphism analysis with the restriction enzyme XbaI and by 2 separate polymerase chain reaction assays; phenotyping was by analysis of in vivo metabolism of the probe drug debrisoquin. RESULTS: No significant difference in the distribution of overall genotypes between the 2 groups was observed. When the frequency of individual alleles was investigated, a significant difference in allele frequency for the CYP2D6D allele (p < 0.005) was observed with fewer patients with RA showing this mutation. Metabolic phenotypes were broadly similar between the patients and controls. However, a number of the patients with RA showed higher than expected metabolic ratios for their particular genotype due to interference by the analgesic dextropropoxyphene in the phenotyping procedure. CONCLUSION: Our findings demonstrate that CYP2D6 activity is not impaired in RA.

Adult↗
PubMed1993

Sulphasalazine in the management of psoriatic arthritis.

There are few 'second-line' drugs available for the treatment of PSA and their use is often limited by toxicity. Thirty-nine patients with active PSA recruited from two rheumatology units were randomly allocated to either enteric-coated sulphasalazine (SASP) or placebo and followed for 24 wk. Six patients in the SASP group and 11 on placebo discontinued therapy before 24 wk. Evaluation of effect of treatment revealed significant improvements in articular index in both groups at 12 wk. By 24 wk the articular index in placebo group was still showing benefit. In addition to articular index the SASP group improved significantly in terms of visual analogue scale, duration of morning stiffness and ESR. SASP is effective in PSA but the partial clinical response to placebo indicates the importance of placebo-controlled studies in this variable disease.

Adolescent↗
PubMed1993

Physiological variations in the urinary excretion of pyridinium crosslinks of collagen.

To further validate measurements of the pyridinium crosslinks of collagen as indices primarily of bone resorption in arthritis and other diseases, the effects of day-to-day and nyctohemeral parallel variations, and of renal impairment have been studied. Day-to-day variations measured over 3 weeks were between 16 and 24% for a group of post-menopausal women. Nyctohemeral variations in crosslink excretion of 10-15% were recorded. Although crosslink excretion relative to creatinine was generally higher in the morning than in the evening, no consistent pattern was observed between healthy male and female volunteers and a group of patients with OA or RA. For patients with impaired renal function, with or without arthritis, there was no correlation between crosslink excretion and either creatinine clearance rates or urinary N-acetyl glucosaminidase activity. These results suggested that there was no direct relationship between renal function, at the glomerular or tubular level, and crosslink excretion.

Adult↗