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Biomedical subjects

G F Watts

Publications and source records attributed to G F Watts.

At least 163 records · Page 9Linked to original sources

Low-molecular-weight proteinuria in insulin-dependent diabetes mellitus: a study of the urinary excretion of beta 2-microglobulin and retinol-binding protein in alkalinized patients with and without microalbuminuria.

The urinary excretion of two low-molecular-weight proteins (beta 2-microglobulin and retinol-binding protein) was measured in 12 insulin-dependent diabetic patients with persistent microalbuminuria and an equal number with normal albumin excretion; reference ranges for the excretion of beta 2-microglobulin (beta 2M) and retinol-binding protein (RBP) were also obtained in 40 non-diabetic subjects. To ensure the stability of beta 2M in urine a urinary pH greater than or equal to 7 was achieved by giving oral sodium bicarbonate. beta 2M and RBP excretion was significantly higher in the diabetics than in the controls (p less than 0.01), but no higher in microalbuminuric than non-albuminuric diabetics. In the diabetics as a group a significant correlation was found between the excretion of beta 2M and RBP (r = 0.53, p less than 0.01), but more patients had an abnormal excretion of beta 2M than RBP (p less than 0.001). No significant correlation was found between the urinary excretion of either low-molecular-weight protein and duration of diabetes, insulin dose, HbA1, urinary glucose excretion or systemic blood pressure. Measured under appropriate alkaline conditions beta 2M appears to be more sensitive than RBP in detecting an abnormality of the renal proximal tubule which may be an early feature of diabetic renal involvement not characterized by microalbuminuria; microalbuminuria may have glomerular and tubular components.

Adolescent↗

Urinary albumin excretion in healthy adult subjects: reference values and some factors affecting their interpretation.

A conventional radioimmunoassay has been used to measure urinary albumin concentration in overnight, recumbent and daytime, ambulant samples from 127 healthy, normotensive volunteers (mean age 33.3 yr SD 12.4; 59 males, 68 females). Reference values were obtained for urine albumin concentration (mg/l), albumin/creatinine ratio (mg/mmol), and albumin excretion rate (microgram/min). The frequency distributions of these variables were positively skewed, but became Gaussian on logarithmic transformation of the data. Albumin excretion was significantly higher in daytime, ambulant samples than in overnight, recumbent samples (p less than 0.001). Surface area was not correlated with urine albumin concentration but it was negatively correlated with urine albumin/creatinine ratio (p less than 0.05) due to the association between surface area and creatinine excretion. Urine albumin concentration was negatively correlated with age, but this was due to a higher urine flow rate in older subjects. There was no significant association with sex or with mean arterial blood pressure in the normal range. Two repeated measurements showed that variability was high and comparable for urine albumin concentration, albumin/creatinine ratio and albumin excretion rate: it was not significantly less in overnight, recumbent than in day-time, ambulant samples.

Adolescent↗

Effective lipid lowering diets including lean meat.

The plasma lipid and lipoprotein responses to two modified isoenergetic diets including meat were studied in 15 free living men with hyperlipidaemia (mean plasma cholesterol and triglyceride concentrations 8.1 and 3.4 mmol/l). A reference diet (diet A, 42% energy from fat, ratio of polyunsaturated to saturated fatty acids (P:S ratio) 0.2) was compared with a fat reduced diet (diet B, 35% energy from fat, P:S ratio 0.5) and with a further fat modified diet supplemented with fibre (diet C, 27% energy from fat, P:S ratio 1.0). Daily intake of meat and meat products (180 g/day) was the same in each dietary period; that in diet A had a fat content typical of the average British diet, whereas that in diets B and C was based on very lean meat and meat products. During consumption of diet B the plasma cholesterol concentration fell by 8.6% and low density lipoprotein cholesterol by 11%. During consumption of diet C plasma cholesterol fell by 18.5% and low density lipoprotein cholesterol by 23.8%. Triglyceride and high density lipoprotein cholesterol concentrations and body weight did not change appreciably during the study. A modified diet including a moderate amount of lean meat and meat products is compatible with a reduced lipoprotein mediated risk of atherosclerotic heart disease.

Cholesterol↗

Side-room tests to screen for microalbuminuria in diabetes mellitus.

Three side-room tests (latex bead immunoagglutination test, LBT; 25% sulphosalicylic acid test, SST; microalbutest, MAT) for the detection of microalbuminuria in diabetics are described and their screening potential and practicability assessed. One hundred insulin-dependent diabetics attending a diabetic clinic provided an early morning urine sample (Albustix-negative) which was subjected to each of the three tests, and urinary albumin concentration (UA) was assayed by RIA. Tests were assessed in random order by two trained operators using a semiquantitative grading scale with 100% concordance between 10 observers. All test results greater than or equal to trace +ve were sufficiently sensitive (sensitivity greater than or equal to 90%) in detecting UA greater than 15 mg/l, but MAT exhibited a significantly reduced specificity (69%) and positive predictive value (58%). For a reference UA greater than 30 mg/l, LBT and SST results greater than or equal to trace +ve and MAT results greater than or equal to +ve showed a sensitivity of 100%, a specificity greater than 85% and a positive predictive value greater than 60%. Reagent shelf-life was shortest with LBT. SST involved centrifugation or filtration. Technical skill required was highest with LBT and lowest with MAT. Costs were slightly higher with LBT than SST and were not available for MAT.

Albuminuria↗

Gemfibrozil in the treatment of resistant familial hypercholesterolaemia and type III hyperlipoproteinaemia.

The efficacy of gemfibrozil in the treatment of resistant familial hypercholesterolaemia and type III hyperlipoproteinaemia was evaluated in 26 individuals over a mean period of 16 months. In the untreated state both disorders are associated with a high frequency of coronary heart disease. In the former, gemfibrozil with a bile acid sequestrant reduced plasma cholesterol by 32%, an incremental decrease of 17% compared with sequestrant therapy alone. In type III, plasma cholesterol was reduced by 40% and plasma triglyceride by 70%, while high-density lipoprotein cholesterol increased by 45%. In none of the patients studied did clinical or biochemical side effects occur.

Cholesterol↗

Nutrient intake in insulin-dependent diabetic patients with incipient nephropathy.

The onset of diabetic nephropathy is characterized by subclinical elevation of urinary albumin excretion, so-called 'microalbuminuria' (M). Dietary assessments were carried out in 15 insulin-dependent diabetic patients with persistent M and an equal number with persistently normal albumin excretion. The groups were matched for sex, age, duration of diabetes, body mass index, insulin dose and glycosylated haemoglobin; there were no significant differences in systemic blood pressure, glomerular filtration rate, blood glucose and serum albumin concentrations between the groups; retinopathy was significantly more frequent in patients with M. Diabetics with persistent M were found to consume a significantly larger amount of fat (expressed as grams and percentage of total energy) and a significantly smaller percentage of total energy as carbohydrate than patients with normal albumin excretion; total dietary energy was larger in those with persistent M, but the difference was not significant. No significant differences were found in protein and fibre intakes between the groups. Our findings suggest that an excess in the dietary consumption of fat relative to carbohydrate might play an important role in the pathogenesis of early nephropathy in insulin-dependent diabetes mellitus. We emphasize the importance of careful attention to nutrient intake in the prevention and treatment of diabetic complications.

Adult↗

Retinol binding protein as a small molecular weight marker of renal tubular function in diabetes mellitus.

A radioimmunoassay has been developed for the measurement in urine of retinol-binding protein (alpha 2-microglobulin) and used as an index of renal tubular function in adult Type 1 (insulin-dependent) diabetics and to define reference ranges in non-diabetic controls. There was a significantly greater excretion (P less than 0.001) of retinol-binding protein in the diabetic group compared to the controls in both overnight and daytime samples. There was a weak positive correlation with albumin excretion (r = 0.33; P less than 0.01) but no correlation with HbA1, duration of diabetes or arterial blood pressure. The results indicate that retinol-binding protein excretion may be increased in diabetic subjects without increased albumin excretion. The possibility therefore exists that renal tubular damage may occur early in diabetic nephropathy without apparent glomerular dysfunction.

Adolescent↗

A simple side-room test to screen for 'microalbuminuria' in diabetes mellitus.

A simplified latex bead immunoagglutination test is described employing the use of commercial antibody. It is practicable, reproducible and valid in screening for 'microalbuminuria' in diabetic patients. Although it is recommended as a side-room test its use should be supplemented where indicated by laboratory-based measurements.

Adult↗

Assessment of new radioimmunoassay kit for determining urinary albumin at low concentrations: comparison with radial immunodiffusion.

The assay characteristics of a new radioimmunoassay kit for determining urinary albumin at low concentrations were studied. The sensitivity for urinary albumin was 2 mg/l, the analytical range 2 to 40 mg/l, and interassay coefficient of variation less than 12%. In a method comparison study entailing diabetic urine samples covering an albumin concentration of 2 to 150 mg/l the kit compared adequately with radial immunodiffusion (mean difference between methods = 2 mg/l; residual standard deviation = 4.6 mg/l), absolute variation between methods increasing with the concentration. The kit required much less skill than radial immunodiffusion but its capital and running cost were higher.

Albuminuria↗

Assessment of immunochemical methods for determining low concentrations of albumin in urine.

Four immunochemical methods (radioimmunoassay, RIA; radial immunodiffusion, RID; immunoturbidimetry, IT; enzyme-linked immunosorbent assay, ELISA) for measuring urinary albumin at low concentrations were assessed for their assay characteristics and practicability. Precision and accuracy were comparable between the methods when studied individually. We made a method comparison, with RIA as reference, using urine samples from diabetic patients with albumin concentrations ranging from 1 to 120 mg/L. There was no significant systematic difference between RID and RIA, but IT and ELISA gave consistently lower values than RIA, the mean differences being 1.8 (p less than 0.01) and 9.7 mg/L (p less than 0.001), respectively. Random error, compared with that for RIA, was in increasing order: RID (residual SD = 3.8 mg/L); IT (4.3 mg/L); ELISA (7.3 mg/L). The difference between the methods increased with the albumin concentration. Operational cost was highest with IT, lowest with RIA. Capital cost was highest with RIA and lowest with RID, which required most technical skill. ELISA had intermediate overall costs.

Albuminuria↗

Treatment of diabetic gastroparesis with oral domperidone.

Three patients with severe diabetic gastroparesis unresponsive to metoclopramide were found to have markedly prolonged gastric half-emptying times (t1/2) using a radionuclide-labelled test meal. They all showed symptomatic improvement and normal t1/2 within one week of taking oral domperidone 10 mg q.d.s. Oral domperidone may have a role in the treatment of severe diabetic gastroparesis particularly in metoclopramide-resistant cases.

Administration, Oral↗

Hypersensitivity to azathioprine in myasthenia gravis.

A patient with myasthenia gravis is described who exhibited hypersensitivity including an apparent acute exacerbation of the underlying disorder when treated with azathioprine. 6-mercaptoprine (6-MP) also produced hypersensitivity which, in contrast, did not manifest as a myasthenic exacerbation.

Azathioprine↗