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Biomedical subjects

A Dawnay

Publications and source records attributed to A Dawnay.

At least 37 records · Page 2Linked to original sources

A radioimmunoassay for human urinary prealbumin.

We describe a validated radioimmunoassay for prealbumin in urine. Using timed overnight urine samples, the normal reference range was less than 10-148 micrograms/L; or less than 1.8-9.6 micrograms/mmol creatinine, excretion in women being significantly greater than in men (P < 0.05); or less than 7.3-114 ng/min with no significant difference in excretion rate between the sexes. Urines exhibited loss of immunoreactivity after storage at -20 degrees C and thawing. No such loss occurred after storage for 4 weeks at 4 degrees C or room temperature. The urinary excretion of prealbumin was highly correlated with that of albumin (r = 0.85), and clearance relative to creatinine was 2 x 10(-6), the same order as that of albumin.

Adolescent↗

Renal and general tolerability of repeated doses of nimesulide in normal subjects.

The renal and general tolerability of nimesulide was studied in 16 healthy men, randomised to 4 groups of 4 subjects. The groups all underwent 2 treatment periods of 7 days each, separated by a washout period of 14 days. The second treatment period was always at a higher dosage level than the first. There were 4 dosage regimens: placebo, and nimesulide 200, 300 and 400mg, all given twice daily by mouth according to a double-blind design. The tolerability of nimesulide was assessed by regular clinical examination, nondirected questions about adverse events, haematological and biochemical screening, and daily urine testing. Plasma and urinary concentrations of Tamm-Horsfall glycoprotein (THG), urinary retinol-binding protein (RBP) and beta-N-acetyl glucosaminidase (NAG) on days 1, 3, 7, and 10 of each period were used as selective indicators of nephrotoxicity. The highest dose of nimesulide (800mg daily) was associated with abdominal pain and indigestion in 5 of 8 recipients. The 400 and 600mg daily dosages were well tolerated. There were no clinically significant alterations in the haematological or biochemical screening tests during the study, and daily urinalysis remained normal throughout. The renal toxicity tests showed no evidence of nephrotoxicity associated with the administration of nimesulide in 14 subjects. The other 2 subjects each had modest increases in either urinary THG or NAG concentrations during treatment with nimesulide 800mg daily, but the results of their other tests remained normal. The study, therefore, showed only equivocal evidence of minor renal toxicity with nimesulide 800mg daily. Nimesulide 400 and 600mg daily were well tolerated in all respects, even though these dosages are higher than those recommended for clinical use.

Adult↗

Microalbuminuria in systemic sclerosis.

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.

Adult↗

The concentrations of transferrin, beta 2-microglobulin, and albumin in seminal plasma in relation to sperm count.

A number of studies have shown a relationship between transferrin levels in seminal plasma and sperm count. In the present study, the levels of transferrin, beta 2-microglobulin and albumin were measured in 171 samples of seminal plasma (50 subjects with normal sperm count; 32 with azoospermia; 49 with oligozoospermia; 10 with polyzoospermia; and 31 vasectomized). All three proteins were related to sperm count. It is concluded that there is a general relationship between seminal plasma proteins and sperm numbers and that some products of the sperm themselves must control the entry of plasma proteins into seminal plasma.

Humans↗

Immunoradiometric assay of atrial natriuretic peptide in unextracted plasma.

We have developed and validated a two-site liquid-phase immunoradiometric assay (IRMA) of atrial natriuretic peptide (ANP) in unextracted human plasma. Both radiolabeled rabbit anti-ANP IgG and polyclonal mouse anti-ANP must bind to ANP for detection, and the assay is specific for peptides with both an intact C-terminus and a disulfide bridge. The assay sensitivity (detection limit) is 0.96 pmol/L, and the working range is 2.3-300 pmol/L, with the hook effect occurring above 500 pmol/L. Results for diluted plasma from normal subjects and from patients with renal failure paralleled the standard curve; analytical recovery of ANP added to such samples averaged 94%. The between- and within-assay CVs at 8 pmol/L were 10% and 5%, respectively. The assay is sufficiently sensitive and precise to detect the postural change in ANP concentrations in normal subjects.

Atrial Natriuretic Factor↗

Renal and gastrointestinal tolerability of lornoxicam, and effects on haemostasis and hepatic microsomal oxidation.

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.

Adult↗

Two regimens of lithium prophylaxis and renal function.

Two regimens of lithium prophylaxis with different pharmacokinetic characteristics were compared under double-blind conditions in 25 bipolar patients in remission already stabilized on lithium, to determine the relative effects of each regimen on renal function. Once-daily lithium carbonate (Priadal), which gives a peak lithium plasma level 2-3 h post-administration with a low level 24 h later, was compared with twice-daily lithium citrate (Litarex), which maintains a steadier 24 h plasma level. Patients were allocated randomly to one of the 2 regimens. They were seen monthly for clinical ratings over the course of 12 months. A comprehensive battery of renal function tests was undertaken at the start of the trial, between 6-9 months after the start and again after 1 year. No significant differences were observed in clinical outcome, side effects or renal function between the 2 regimens.

Acetylglucosaminidase↗

Micro-ELISA for the quantitation of human urinary and serum retinol-binding protein.

A highly sensitive enzyme linked immunoadsorbent assay for determining retinol-binding protein in urine and serum is described. Commercially available reagents are used. The standard curve ranges from 1.2-24 micrograms/l, recovery of retinol-binding protein added to urine was 99-102% (n = 10) and dilution of urine was linear. The within-assay coefficient of variation ranged from 1.2-3.1% and the day-to-day coefficient of variation from 9.2-10.5% depending on concentration. The correlation with urinary retinol-binding protein determined by radioimmunoassay was good (n = 90, r = 0.95). In vitro experiments show that retinol-binding protein is stable in urine with pH 5.2.

Enzyme-Linked Immunosorbent Assay↗

Urinary excretion of albumin and retinol-binding protein during normal pregnancy.

In a cross sectional study of 88 pregnant women urinary excretion of albumin, when expressed as a ratio to creatinine concentration, was not significantly different from that in a non-pregnant control group of similar age (p greater than 0.05) and did not change significantly during pregnancy. Only when albumin excretion was expressed as a fractional clearance was the urinary excretion significantly increased in the third trimester compared with the first trimester (p less than 0.05), although it was still not significantly different from that in the non-pregnant control group. Excretion of retinol-binding protein was significantly increased during all three trimesters of pregnancy (p less than 0.01 in each case) and more so in the second and third trimesters than in the first. It is concluded that the increased total protein excretion that has been described during pregnancy is not explained by an increased excretion of albumin which remains essentially normal. In contrast, the tubular absorption of proteins is decreased.

Albuminuria↗

The effect of a synthetic polypeptide on the renal handling of protein in man.

Haemaccel is a synthetic polymer of partially degraded gelatin and a widely used plasma volume expander. The effect of a 17.5 g infusion of Haemaccel on protein excretion was investigated in four normal subjects. The urinary excretion of two low molecular weight proteins, retinol-binding protein and beta 2-microglobulin, increased 1000- and 500-fold respectively above the values found after administration of saline as a control. The urinary excretion of albumin did not change significantly (P greater than 0.5). In the hour after Haemaccel administration the excretion of the two low molecular weight proteins approached at least 50% of a predicted filtered load. This effect of Haemaccel may be due to inhibition of proximal tubular uptake or transport of the two proteins. Absence of any effect on albumin excretion suggests alternative mechanisms for its tubular reabsorption. Haemaccel may be a valuable new agent for the study of renal tubular protein metabolism.

Acetylglucosaminidase↗