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Biomedical subjects

C Astbury

Publications and source records attributed to C Astbury.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1991

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↗
PubMed1990

Infection risks in hospital staff from blood: hazardous injury rates and acceptance of hepatitis B immunization.

A questionnaire survey of 1800 clinical health care staff was undertaken to determine hazardous injury rates and uptake of hepatitis B vaccination. The overall sharps injury rate was 116 injuries per 100 staff per year. Full-time doctors had the highest rates. Surgical procedures were the commonest cause of accidental injury (58 per cent) and 30 per cent of all sharps injuries were attributable to careless handling. Injuries caused by bites and scratches from patients occurred mainly in nurses and auxilliaries in psychiatric and geriatric wards (115/100 staff per year). Twenty-four per cent of respondents had received a full course of hepatitis B vaccine and 51 per cent of the remainder were planning to have, or were in the process of receiving, a course. The most frequent reason given for not being vaccinated was lack of information about vaccination. This survey reveals injury rates higher than those observed in previous reports, particularly in doctors, and shows a need for more information and advice about hepatitis B infection and vaccination to be targeted to health care workers at risk.

Accidents, Occupational↗
PubMed1990

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↗
PubMed1990

Comparison of the single dose pharmacokinetics of sulphasalazine in rheumatoid arthritis and inflammatory bowel disease.

The pharmacokinetics of sulphasalazine and its principal metabolites in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) were compared. Patients with RA had a significantly greater concentration of plasma sulphapyridine than patients with IBD (medians 14.0 micrograms/ml and 7.4 micrograms/ml respectively). Patients with RA also tended to maintain a higher plasma sulphapyridine concentration with time, as determined by the area under the curve (AUC), but a lower plasma sulphasalazine AUC than patients with IBD. It is suggested that more sulphasalazine may be presented to the lower bowel for cleavage to sulphapyridine and 5-aminosalicylic acid in patients with RA than in IBD. Patients with RA may also have impaired metabolism of sulphapyridine as a consequence of their disease. Together these factors may contribute to higher peak circulating sulphapyridine concentrations and may be responsible for the higher incidence of side effects of sulphasalazine treatment in patients with RA than in patients with IBD.

Adult↗
PubMed1988

Kinetic investigations into the possible cause of low serum histidine in rheumatoid arthritis.

To investigate the cause of low serum histidine in rheumatoid arthritis (RA) single oral and intravenous doses of L-histidine were administered to patients with active RA, and to an equal number of age and sex matched control subjects. In the first study 13 patients and their controls received a 100 mg kg-1 dose of L-histidine as an aqueous slurry. Significant differences were seen in body weight, predose baseline serum histidine concentration, Cmax, t1/2, and area under curve, AUC0-infinity. In a second study six patients and six controls each received a 50 mg kg-1 dose of L-histidine both orally and intravenously on two separate occasions. The patients with RA had a lower baseline serum histidine concentration, a lower volume of distribution, and a shorter plasma half life than the controls, but these differences were not statistically significant. No difference was seen in bioavailability or clearance. Low serum histidine in RA is unlikely to be due to malabsorption from the gut, uptake by abnormal gut flora, or increased metabolism.

Adult↗
PubMed1988

Co-trimoxazole in rheumatoid arthritis: a comparison with sulphapyridine.

The antirheumatoid activity of sulphasalazine and sulphapyridine may result from their antibacterial properties. The second line activity of sulphamethoxazole, in the form of cotrimoxazole (CTZ), has been investigated by treatment of 13 patients with RA for 24 weeks with CTZ (480 mg three times a day). The drug was found to be poorly tolerated, only five of the thirteen patients recruited completing the study. High circulating concentrations of sulphamethoxazole were found, with mean (SD) steady state serum concentrations reaching 54.02 (23.38) micrograms/ml. A significant reduction in serum IgM from 280 to 130 IU/l was observed, but otherwise disease activity remained unchanged or deteriorated throughout the course of the study. In contrast, patients with RA treated with sulphapyridine (1.25 g a day) showed improvement in disease activity. The results argue against an antibacterial mechanism of action for sulphasalazine and sulphapyridine in rheumatoid arthritis, unless this occurs at a site inaccessible to sulphamethoxazole.

Arthritis, Rheumatoid↗
PubMed1987

Sulphasalazine alone or in combination with D-penicillamine in rheumatoid arthritis.

Thirty patients (22 women) with active rheumatoid arthritis participated in an open study of 6 months' treatment with either enteric-coated sulphasalazine (SASP) or SASP plus D-penicillamine (DPA). Patients were assessed at regular intervals using a number of clinical and biochemical tests designed to detect specific antirheumatic activity. There were significant improvements in clinical and laboratory variables with both regimens consistent with second-line activity. Improvements were greater and more numerous with combination therapy. At the end of the trial period, there were nine 'responders' in the SASP/DPA group but only six in the SASP group. Neither efficacy nor toxicity could be related to patient acetylator status. Nausea and dyspepsia were frequent problems with both treatment regimens but dysgeusia and thrombocytopenia were confined to the SASP/DPA group. Study withdrawals were twice as common with combination therapy. These results suggest that a combination of SASP and DPA is more potent than SASP alone but at the expense of poorer patient tolerance.

Arthritis, Rheumatoid↗
PubMed1986

Prednisolone pharmacokinetics in patients with rheumatoid arthritis, polymyalgia rheumatica and asthma.

The pharmacokinetic profile of a single 10 mg oral dose of prednisolone was studied in three groups of six patients with rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) and bronchial asthma (BA) who were already receiving steroid therapy. A fourth group of age and sex-matched normal controls was also studied. Kinetic parameters (including elimination half-life, area under the plasma concentration curve, apparent volume of distribution and total body clearance) were similar for all four groups but there was considerable inter-subject variability. The correlations between these kinetic parameters and age, body weight and serum albumin were poor. The results suggest that any differences in the effects of corticosteroids in these inflammatory diseases are unlikely to be due to pharmacokinetic factors. The duration of steroid therapy and the reduction in patient mobility would appear to be more likely explanations for the reduction in bone mass observed in patients with RA.

Administration, Oral↗
PubMed1986

Measurement of the cross linking compound, pyridinoline, in urine as an index of collagen degradation in joint disease.

An enzyme linked immunoassay (ELISA) for the collagen cross link, pyridinoline, has been developed using affinity purified antibodies, with a sensitivity down to about 0.1 ng of cross link. Measurements of urinary pyridinoline were made in patients with rheumatoid arthritis (RA), osteoarthritis (OA), and a control group showing no signs of joint disease. Expressed relative to creatinine values, pyridinoline was significantly increased in both RA and OA groups compared with controls: these differences were much larger than could be attributed to any age related effects or to changes in urinary creatinine concentrations. These findings were confirmed by analysis of a series of 24 h urine collections which showed that the total pyridinoline excretions were significantly higher in both RA and OA groups than in the controls. As pyridinoline is much more prevalent in cartilage than in bone collagen, measurement of this compound in urine may provide an index for monitoring the increased joint destruction that occurs in arthritic disease.

Adult↗
PubMed1986

5-Aminosalicylic acid or sulphapyridine. Which is the active moiety of sulphasalazine in rheumatoid arthritis?

Thirty patients with active rheumatoid arthritis participated in an open study of 6 months' treatment with either 5-aminosalicylic acid or sulphapyridine, the two moieties of sulphasalazine. Patients were assessed at regular intervals using a number of clinical and biochemical tests designed to detect specific antirheumatic activity. Patients taking sulphasalazine showed significant improvement in most parameters of disease activity, but those taking 5-aminosalicylic acid did not improve despite the fact that high serum concentrations of 5-aminosalicylic acid and acetyl 5-aminosalicylic acid were achieved. These results suggest that sulphapyridine is the active moiety of sulphasalazine. Its possible mode of action is discussed. Nausea was a frequent problem in patients taking sulphapyridine. Unless this problem can be overcome, sulphapyridine is unlikely to offer any therapeutic advantages over sulphasalazine in the treatment of rheumatoid arthritis.

Adult↗
PubMed1986

A study to determine the active moiety of sulphasalazine in rheumatoid arthritis.

Thirty patients with active rheumatoid arthritis (RA) participated in an open study of 6 months' treatment with either 5-aminosalicylic acid (5-ASA) or sulphapyridine (SP), the two moieties of sulphasalazine (SASP). Patients were assessed at regular intervals using clinical and biochemical tests designed to detect specific antirheumatic activity. Patients taking SP showed significant improvement in disease activity, but those taking 5-ASA did not improve, despite the fact that high serum concentrations of 5-ASA and acetyl 5-ASA were achieved. These results suggest that SP is the active moiety of SASP. Its possible mode of action is discussed. Nausea was a frequent problem in patients taking SP. Unless this can be overcome, SP is unlikely to offer any therapeutic advantages over SASP in the treatment of RA.

Adult↗
PubMed1986

A parallel group comparison of tenoxicam and piroxicam in patients with ankylosing spondylitis.

Tenoxicam (20 mg/day) and piroxicam (20 mg/day) were compared in a double-blind, parallel group study over 4 weeks in 30 patients with ankylosing spondylitis. Both tenoxicam and piroxicam reduced spinal pain, but the improvement was greater with piroxicam. Tenoxicam and piroxicam were equally effective at improving duration of morning stiffness. Slight improvement was seen with other symptoms with both treatments. Patients were slightly more tolerant of piroxicam than tenoxicam and most patients elected to continue on their particular therapy at the end of the study.

Administration, Oral↗
PubMed1985

A double-blind controlled trial of etretinate (Tigason) and ibuprofen in psoriatic arthritis.

Etretinate (Tigason) and ibuprofen have been compared in a double-blind controlled trial in psoriatic arthritis to see if we could confirm a specific action for this vitamin A derivative suggested from earlier uncontrolled studies. Eleven out of 20 patients completed 24 weeks of therapy with etretinate (up to 0.5 mg/kg/day) whereas only 1/20 patients completed 24 weeks of therapy with ibuprofen alone. Etretinate improved skin lesions, and this may have encouraged patients to persist with it. Improvement of statistical significance was seen for articular index in both groups. In addition significant improvement in ESR, haemoglobin, C-reactive protein, and histidine occurred in the etretinate group. The main side effects of etretinate (which may preclude its use at a higher dose in this condition) included cracked and dried lips and sore mouth.

Adolescent↗