British Society for Rheumatology and british health professionals in Rheumatology guideline for the management of rheumatoid arthritis (the first two years).
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Biomedical subjects
Publications and source records attributed to E Lamb.
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1. Chronic use of hyperosmolar glucose solutions in continuous ambulatory peritoneal dialysis may cause glycation of peritoneal structural proteins which could contribute to membrane dysfunction and ultrafiltration failure. To determine whether glycation can occur in the environment of the dialysate, we have carried out studies using albumin as a model protein. 2. Glycated albumin was measured in the serum and dialysate of 46 patients on continuous ambulatory peritoneal dialysis (31 non-diabetic patients, 15 diabetic patients). Dialysate and serum glycated albumin (ranges 1.0-12.7% and 0.9-10.2%, respectively) were related to each other (r = 0.988, P < 0.001), but dialysate glycated albumin was significantly higher than serum glycated albumin (P < 0.0001), with the dialysate to serum glycated albumin ratio being greater than unity in 76% of patients (mean ratio 1.14). This implies either preferential transfer of glycated albumin across the peritoneal membrane or intraperitoneal glycation during the dwell period. 3. In vitro, significant glycation occurred in dialysate during a 6 h incubation period (P < 0.01) at a rate related to the glucose concentration in the dialysate (rs = 0.63, P < 0.05). The glycation rate was not significantly affected (P = 0.05) by factors other than the glucose concentration. 4. Our results demonstrate that protein glycation occurs within the peritoneum during continuous ambulatory peritoneal dialysis. Further studies are required to establish the relationship of glycation of structural proteins in the peritoneal membrane to membrane function.
The effect of uraemia on protein glycation was studied by measuring glycated albumin and fructosamine in 50 non-diabetic dialysis patients (31 continuous ambulatory peritoneal dialysis, CAPD, 19 haemodialysis). After correction for serum albumin concentration, glycated albumin (g/100 g) was increased in the haemodialysis group (1.94 +/- 0.40) compared with both CAPD patients (1.46 +/- 0.37; p < 0.001) and controls (1.52 +/- 0.29; p < 0.001), but did not differ between CAPD patients and controls (p > 0.05). Serum fructosamine, corrected for either serum albumin or total protein concentration (mumol/100 g), was raised in CAPD (828 +/- 90, 386 +/- 41, respectively) and haemodialysis patients (802 +/- 123, 391 +/- 42, respectively) compared with controls (609 +/- 69, 332 +/- 27, respectively; p < 0.0001 in all cases), but did not differ between the two dialysis groups (p > 0.05). A single haemodialysis cycle had no effect on the measurement of glycated albumin or fructosamine (p > 0.05). The results confirm that glycated protein levels are generally raised in dialysis patients. In CAPD patients, altered albumin metabolism resulting from large peritoneal losses is likely to have caused a decrease in the amount of albumin glycated, an effect less apparent on the concentration of fructosamine because of the additional contribution of glycated globulins.
A prospective study was performed to determine urinary albumin excretion in a group of 28 patients with systemic sclerosis. At the initial screen one patient had proteinuria and three had microalbuminuria. One year later these abnormalities persisted and in two of of the patients serum creatinine had significantly increased. In addition, a further three patients had developed microalbuminuria. In a control group of 10 patients with primary Raynaud's disease none had microalbuminuria. In a second control group of 16 patients with unrelated skin diseases one patient had microalbuminuria and one proteinuria, but both these patients had a history of hypertension. It is concluded that microalbuminuria is more common in patients with systemic sclerosis than in patients of equivalent age with other dermatological conditions but no vascular disease.
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Affinity chromatography on m-aminophenyl boronate columns together with albumin measurement by radioimmunoassay has been validated as a method for determining glycated albumin in serum and urine. Optimisation of sample volume and of elution buffer composition and volume ensured reproducibility of results. Fructosamine assay confirmed the absence of glycated albumin species from the non-glycated fraction. It was possible to elute the glycated fraction from the affinity columns with Tris or glycine which do not contain 1,2 diols but have similar functional groups. Column affinity was, therefore, not specific for glycated protein moieties. Inhibition of binding by glucose, and other small molecules in urine, necessitated ultrafiltration or dialysis of samples before analysis. Reference ranges for glycated albumin in non-diabetic subjects were 0.6-1.8% in serum and 0.9-2.6% in urine. In patients with diabetes mellitus, glycated albumin ranged from 1.4-10.9% in serum and from 1.5-12.5% in urine.
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Three separate studies were carried out to assess the renal and gastrointestinal tolerability of lornoxicam, and its effects on haemostasis and hepatic microsomal oxidation. Haemostasis and hepatic microsomal oxidation. Six men and 6 women had salivary antipyrine half-life determined before and on the last day of 14 days' treatment with lornoxicam 4 mg twice daily. Haemostasis, coagulation and thrombolysis were assessed ex vivo using a haemostatometer before and on Day 14 of lornoxicam treatment. Lornoxicam 4 mg twice daily for 14 days had no significant influence on antipyrine elimination half-life or haemostasis, coagulation and thrombolysis. Renal tolerability. Three groups of 8 healthy young men received respectively 4, 6 and 8 mg lornoxicam twice daily by mouth for 22 days. Nephrotoxicity studies on serum and urine were done repeatedly before, during and after lornoxicam treatment. Serum and urine creatinine, serum Tamm-Horsfall glycoprotein (THG), and urine n-acetylglucosaminidase (NAG), THG and retinol binding protein (RBP) concentrations showed sporadic values outside the laboratory reference range, but these were not in any subject temporally related to drug treatment and were unrelated to dose. Urine microscopy was unremarkable. Thus this study yielded no evidence that lornoxicam has any nephrotoxic effects in healthy young men receiving doses up to 8 mg twice daily for 22 days. Gastrointestinal blood loss and endoscopy. The gastrointestinal effects of lornoxicam 4 mg, indomethacin 50 mg or placebo twice daily for 29 days were evaluated in 45 healthy men. After an initial endoscopic examination, subjects underwent 51Cr red cell labelling. Complete daily faecal collections were then made from Days 6-12, 20-26 and 34-40. Treatments were given from Days 13-41. Endoscopy was repeated 4-8 h after the last dose of medication. Faecal blood loss during lornoxicam treatment was greater than placebo and less than indomethacin, but within- and between-subject variability was such that the differences were not statistically significant. Endoscopic findings were normal in most subjects before and after all 3 treatments.
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