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Biomedical subjects

R D Situnayake

Publications and source records attributed to R D Situnayake.

At least 37 records · Page 2Linked to original sources
PubMed1991

Further evidence of lipid peroxidation in post-enteropathic haemolytic-uraemic syndrome.

Lipid peroxidation may play a role in the pathogenesis of the haemolytic-uraemic syndrome (HUS). Thirteen children with the post-enteropathic form of HUS were studied using conjugated diene lipids as markers of in vivo lipid peroxidation. Levels of total conjugated diene lipids and 9,11-linoleic acid, the principal conjugated diene in human plasma, were greater in the acute phase of this disorder than in controls. The ratio of plasma vitamin E to lipid was lower than that in children with other renal diseases, and the expected positive correlation between vitamin E and lipids did not hold for HUS patients. These data provide further evidence of lipid peroxidation in HUS and a disturbance in the metabolism of the principal lipid-bound anti-oxidant vitamin E.

Adolescent↗
PubMed1991

Chain breaking antioxidant status in rheumatoid arthritis: clinical and laboratory correlates.

The ability of fresh sera to resist attack by peroxyl radicals (TRAP) was found to be significantly lower in 20 patients with rheumatoid arthritis (RA) than in 20 healthy controls, consistent with the existence of a redox stress in RA imposed by inflammation. TRAP values in RA varied inversely with a combination of visual analogue pain scale, duration of early morning stiffness, grip strength, and articular index (reflecting inflammatory activity) using multiple linear regression analysis. The concentration of the antioxidant vitamin ascorbic acid was lower in RA plasma and the oxidation-reduction equilibrium of ascorbic acid was disturbed, giving further support to the existence of a redox stress. The major determinant of TRAP in vitro was found to be serum uric acid in RA and serum vitamin E in controls. Serum urate concentration in RA correlated inversely with oxidative changes in serum albumin and IgG. It is suggested that serum urate might have an antioxidant role under certain conditions by limiting free radical induced oxidative changes to protein during inflammation.

Arthritis, Rheumatoid↗
PubMed1990

Absence of correlations between indices of systemic inflammation and synovial fluid interleukin 1 (alpha and beta) in rheumatic diseases.

There are two forms of the cytokine interleukin 1 (IL1), produced by two distinct genes encoding a neutral (IL1 beta) and an acidic (IL1 alpha) peptide. They have powerful pro-inflammatory, immunopotentiating, catabolic and arthritogenic properties in vivo and have been implicated in the pathogenesis of rheumatic diseases. In this study, using specific immunoassays, we have measured both IL1 alpha and IL1 beta levels in synovial fluids (SF) from a large number of patients with different rheumatic diseases. Biologically significant levels of both cytokines were found in SF from patients with different forms of arthritis, but no correlations were found with any of the measures of disease activity that we tested. We also describe the presence in joint exudates of biological inhibitor(s) that neutralize IL1-induced T-cell activation. This is the first report of IL1 alpha and IL1 beta measurements in the same synovial exudates and also of the comparison of local levels of these cytokines with conventional indices of systemic inflammation.

Arthritis↗
PubMed1990

Lipid peroxidation and hepatic antioxidants in alcoholic liver disease.

The generation of hepatic liver peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. To investigate this hypothesis, lipid extracts from hepatic needle biopsy specimens from alcoholic subjects were examined for evidence of lipid peroxidation by measuring total conjugated dienes by derivative spectroscopy and, after hydrolysis of hepatic lipid extract and reverse phase high performance liquid chromatography, the molar ratio between a diene-conjugated linoleic acid isomer (18:2 (9,11)) and the parent linoleic acid isomer (18:2(9,12)). Changes were related to hepatic histology, iron deposition, glutathione and vitamin E values. Derivative spectroscopy minima suggestive of diene conjugation were identified at 233 and 242 nm and correlated weakly, suggesting these two minima may represent different classes of lipid dienes. There was a weak relation with inflammatory histological changes in the biopsy specimen but no correlation with hepatic iron grade, glutathione, or vitamin E lipid ratio. The proportion of 18:2(9,11) linoleic acid in hepatic lipids correlated significantly with inflammatory histological features and inversely with hepatic glutathione. Furthermore, hepatic glutathione was lower in biopsy specimens with greater iron staining. The ratio of vitamin E to lipid was not related to histological group, inflammation, or iron grade. These findings suggest that excess alcohol consumption leads to hepatic inflammation and lipid peroxidation.

Antioxidants↗
PubMed1990

Measurement of conjugated diene lipids by derivative spectroscopy in heptane extracts of plasma.

A series of experiments are described which show that second derivative spectroscopy can be used to quantify conjugated lipid dienes as markers of lipid peroxidation in heptane extracts of plasma from patients with rheumatoid arthritis, osteoarthritis, and healthy controls. Results obtained by this method gave reasonable agreement with those derived from the measurement of simple absorbance in chloroform/methanol extracts. Two minima were observed in the derivative spectrum of plasma lipid extracts. These minima occurred at 233 and 241 nm and corresponded to absorbance maxima in the conventional UV spectrum. Using a combination of phospholipase hydrolysis, reverse phase high performance liquid chromatography (HPLC) and second derivative spectroscopy we confirmed that these two minima can be attributed to a single fatty acid (9 cis-, 11 trans-linoleic acid) shown previously to account for greater than 90% of diene conjugation in human plasma samples. When the biological isomer 9 cis-, 11 trans-linoleic acid was separated by reverse phase HPLC from the mixture of other plasma phospholipid-2-esterified fatty acids we observed a change in derivative spectroscopy minima from 233 and 241 nm to 228 and 237 nm. Minima at the latter two wavelengths were also seen with pure preparations of the Paint Research Isomer (9 trans-, 11 trans-linoleic acid) which eluted later than biological 9 cis-, 11 trans-linoleic acid using reverse phase HPLC, suggesting that the absorption spectra of these pure cis-, trans and trans, trans dienes are similar but can be altered by the presence of other fatty acids in the extract.

Adult↗
PubMed1990

Clinical and laboratory effects of prolonged therapy with sulfasalazine, gold or penicillamine: the effects of disease duration on treatment response.

Serial observations for up to 5 years of clinical score (a subjective global assessment), serum C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were analyzed in 3 groups of patients with active rheumatoid arthritis (RA) requiring treatment with a second line drug. The groups comprised 315 patients (243 women, 72 men) who had sulfasalazine (SAS); 203 patients (141 women, 62 men) who had sodium aurothiomalate (gold) and 163 patients (131 women, 32 men) who had penicillamine. The groups matched in most respects but the gold group had a smaller proportion of women, a shorter median disease duration and a higher median CRP than the remaining 2 groups. The penicillamine group contained a higher proportion of seropositive patients. In each group there were significant improvements in clinical score, CRP and ESR for all time points from 6 to 30 months; these improvements were maintained for longer (up to 60 months for SAS) in the SAS and gold groups but the differences between the drugs after 30 months were probably a consequence of falling number of patients, not differing drug potencies. The mean ESR and CRP levels fell to about 30 mm/h and 20-30 mg/l, respectively. Response was defined as (1) treatment duration greater than 6 months, (2) clinical score improvement greater than 4 by 6 months, (3) ESR fall to less than 30 mm/h by 6 months. By these criteria 142 of 681 patients (20.9%) responded; the response rates were SAS 20.3%, gold 24.1%, penicillamine 17.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗
PubMed1988

Can 'disease modifying' drugs influence outcome in rheumatoid arthritis?

The treatment of rheumatoid arthritis with disease modifying drugs is based on the hypothesis that they exert a more profound effect on the disease process than non-steroidal anti-inflammatory drugs. Short-term studies of disease modifying drugs show significant clinical and laboratory improvements in comparison to placebo. Longer-term studies suggest that this improvement is not maintained. Attempts to assess the effect of disease modifying and immunosuppressive drugs on radiological progression suggest that they may have a week protective effect, but there is no evidence to suggest that this is maintained in the long term. Studies of corticosteroid therapy indicate that in large doses it possesses disease modifying properties and is capable of retarding radiological progression. The benefit-risk ratio of such doses is unacceptable. Lower doses have not yet been adequately investigated. Rheumatologists should regard existing suppressive agents as moderately effective in the short term. Few patients remain on single drug therapy for prolonged periods and available evidence does not suggest that these drugs are capable of altering the long-term outcome of rheumatoid arthritis.

Adrenal Cortex Hormones↗
PubMed1988

Effects of rifampicin with and without isoniazid in rheumatoid arthritis.

A patient with rheumatoid arthritis (RA) experienced great improvement in her RA when given antituberculous treatment for pulmonary tuberculosis (TB). Two of the drugs used in TB, rifampicin and isoniazid, include immunomodulatory effects among their properties. To investigate whether these drugs have any effect in RA, we studied 20 patients who were given either rifampicin 600 mg daily (10 patients) or rifampicin 600 mg with isoniazid 300 mg daily (10 patients). Eighteen patients completed at least 3 months' treatment. Six of the 7 patients with early RA (less than 3 years) improved; their median erythrocyte sedimentation rate fell from 43.5-10 mm/h (p = 0.036) and median serum C-reactive protein from 40-0 mg/l (p = 0.036). Eleven patients with longer histories of RA did not improve. Our results suggest rifampicin with or without isoniazid may be effective in RA.

Adolescent↗
PubMed1987

Long-term treatment of rheumatoid arthritis with sulphasalazine, gold, or penicillamine: a comparison using life-table methods.

Life-table analysis was applied to the records of 317 patients with rheumatoid arthritis (RA) treated with sulphasalazine (SAS), 201 treated with sodium aurothiomalate (gold), and 163 with penicillamine. They comprised all those treated in our department with these drugs between January 1973 and July 1984. Risks of treatment termination for all reasons were similar for each drug at five years (gold 92%, penicillamine 83%, SAS 81%). The risk of treatment termination due to inefficacy was less for gold (29.5%) than for penicillamine (38.1%) or sulphasalazine (41.2%). Adverse effects, however, led to withdrawal of gold in 57%, penicillamine in 41.2%, and SAS in 37%; the most effective drugs appeared most toxic. Serious adverse effects were much more common in association with gold (17.4%) and penicillamine (12.3%) than with SAS (1.6%). Sulphasalazine appears as well tolerated over long periods in RA as gold or penicillamine and is associated with fewer serious adverse effects; of these drugs, it might therefore be considered the agent of first choice.

Actuarial Analysis↗
PubMed1987

Evidence for lipid peroxidation in man following paraquat ingestion.

Four patients were investigated for evidence of lipid peroxidation between 4.5 and 36 h (mean 22 h) after ingestion of paraquat by measuring plasma phospholipid-2-esterified, diene-conjugated 18:2 delta 9,11-linoleic acid (9,11-LA) and expressing it also as a ratio R (9,11-LA/9,12-LA X 100) of the 'parent' linoleic acid. The mean value for R was 4.73 (range 3.7-7.1) at presentation and 6.91 at peak values (range 3.8-13.4) which occurred at a mean of 34 h after ingestion. Both values were significantly higher (P less than 0.001) than that of 107 healthy controls (1.94, range 0.67-3.8). Parallel changes in plasma vitamin E and 9,11-LA occurred in the 2 patients in whom serial measurements were made suggesting an involvement of vitamin E in the formation of this isomer. These findings support the hypothesis that lipid peroxidation occurs during paraquat poisoning in man and the early appearance of 9,11-LA suggests that it may be a primary event.

Adult↗
PubMed1986

The use of different lipids to express serum tocopherol: lipid ratios for the measurement of vitamin E status.

Plasma tocopherol was measured in 85 alcoholic patients and 40 control subjects from a local factory. Cholesterol, triglycerides and phospholipids were measured individually and summed to give an estimate of total serum lipids. Plasma tocopherol concentrations of the alcoholics were significantly lower than those of the controls and showed wide variation from marked deficiency to the upper limit of the normal range. Using regression analysis, 1.11 mumol tocopherol/mmol total lipids were calculated as the threshold of deficiency equivalent to 0.8 mg tocopherol/g total lipid established by Horwitt et al. The sensitivity and specificity of other tocopherol:lipid ratios for identifying vitamin E deficiency was compared with the tocopherol:total lipid ratio. Thresholds of deficiency for the different tocopherol:lipid ratios were calculated. The tocopherol:cholesterol+triglyceride ratio was found to be almost as powerful in identifying vitamin E deficiency as the tocopherol:total lipid ratio (sensitivity 95%, specificity 99%). Of the tocopherol:individual lipid ratios, the tocopherol:cholesterol ratio gave the best results (sensitivity 86%, specificity 94%).

Alcoholism↗