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Biomedical subjects

R Beetham

Publications and source records attributed to R Beetham.

At least 19 recordsLinked to original sources

Increased urinary albumin and retinol-binding protein in type I diabetes. A study of identical twins.

OBJECTIVE: Indexes of early renal glomerular and tubular dysfunction have been demonstrated in type I diabetes, but it remains uncertain whether such changes are genetically determined or are secondary to the disease process. We therefore undertook to study whether early markers of renal dysfunction are a consequence of type I diabetes or inherited. RESEARCH DESIGN AND METHODS: We estimated both urinary albumin excretion (UAE) and urinary retinol-binding protein (RBP) in 51 identical twin pairs discordant for type I diabetes and in 51 matched control subjects. RESULTS: UAE and RBP were significantly higher in the diabetic twins than in their nondiabetic co-twins (P < 0.0001 and P < 0.0002, respectively). Seven diabetic twins had elevated UAE, but none of the nondiabetic co-twins did. In a subgroup of 44 twins with normal UAE (albumin excretion rate < 20 micrograms/min), diabetic twins had both a higher albumin excretion function (median [range]; 0.64 [0.18-2.74] mg/mmol creatinine) than their nondiabetic co-twins (0.48 [0.24-1.40], P < 0.01) and higher levels of RBP excretion (10.4 [4.0-167.0] micrograms/mmol creatinine) than their nondiabetic co-twins (7.5 [0.97-23.0], P < 0.05). Values between twins of a pair were significantly correlated for RBP (r = 0.36, P < 0.05) but not for UAE (r = 0.13). CONCLUSIONS: These results suggest that in type I diabetes, an index of renal tubular function (RBP), but not glomerular function (UAE), is influenced by shared genetic and nongenetic factors. Type I diabetes can affect renal tubular function even when glomerular function is normal. We conclude that neither the increased UAE nor urinary RBP found in type I diabetes is inherited independently of the diabetes process.

Adult

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

Urinary albumin and low molecular weight protein excretion in the nephrotic syndrome--sequential studies during corticosteroid treatment.

In a preliminary investigation into the behaviour of low molecular weight proteins in the nephrotic syndrome, we have measured urinary concentrations of albumin, alpha-1-microglobulin (alpha 1-m) and retinol-binding protein (RBP) in six children for up to 11 days during the course of steroid therapy for nephrotic syndrome. The results in part support the concept of independent proximal tubular absorption of albumin and low molecular weight proteins, and indicate that in the nephrotic syndrome the excretion of RBP and alpha 1-m, two generally accepted markers of tubular proteinuria, is anomalous.

Adrenal Cortex Hormones

Influence of energy and nitrogen contents of enteral diets on nitrogen balance: a double blind prospective controlled clinical trial.

Results of recent controlled studies show that because of difficulties in administering adequate quantities of enteral diet, positive nitrogen balance is not consistently achieved during enteral feeding. In order to determine whether nitrogen balance can be improved in routine clinical practice by prescribing enteral diets containing higher concentrations of nutrients, 118 patients with normal gastrointestinal function needing enteral nutrition were randomised to receive daily 21 of one of three polymeric diets: Standard diet (1.0 kcal/ml; 6.3 gN/l), Energy Dense diet (1.5 kcal/ml; 7.8 gN/l), and Energy-Nitrogen Dense diet (1.5 kcal/ml; 9.4 gN/l. The three diets, administered by continuous nasogastric infusion, were equally well tolerated. Results were analysed only for patients fed five or more days and who received at least 60% of prescribed enteral diet (n = 42). Positive nitrogen balance was achieved only in the patients receiving the Energy-Nitrogen Dense diet (n = 16; + 1.6 (SE) 0.6 gN/d, compared with the Standard diet (n = 12; -3.8 (1.1) gN/d; p less than 0.001), and the Energy Dense diet (m = 14; -1.9 (0.8) gN/d; p less than 0.005). As the findings of this prospective controlled trial show that positive nitrogen balance was not consistently achieved by administering 21 enteral diet containing up to 15.6 gN, consideration could, therefore, be given to routinely using enteral diets containing up to 9.4 gN/l.

Adolescent

Urine concentrations of apolipoprotein AI in renal tubular proteinuria.

To test the hypothesis that a significant proportion of apolipoprotein AI (apoAI) metabolism occurs through glomerular filtration of free apoAI in serum and subsequent renal tubular metabolism, we have examined the urine concentration of apoAI in three situations in which proximal tubular reabsorption of another protein metabolized in this manner and retinol-binding protein (RBP) was impaired. Following infusion of a cross-linked gelatin polymer (Haemaccel) in four normal subjects, urine RBP excretion (normally about 100 micrograms/L), was between 14 and 46 mg/L, while urine apoAI excretion was less than 0.5 mg/L. On the third day following cardiac surgery involving Haemaccel infusion, urine RBP was between 27 and 159 mg/L while urine apoAI excretion was again less than 0.5 mg/L. In 16 samples from eight patients recently transplanted with allograft kidneys, urine RBP was between 9 and 70 mg/L, whereas in only two samples was apoAI detected in the urine at 0.5 mg/L. These results have been taken to indicate that significant metabolism of apoAI through glomerular filtration and tubular absorption is unlikely to occur in humans.

Apolipoprotein A-I

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

Studies on the mechanism of action of dioctyl sodium sulphosuccinate in the human jejunum.

An intestinal perfusion technique has been used to investigate the mechanism of action of the laxative, dioctyl sodium sulphosuccinate, in the human jejunum. Dioctyl sodium sulphosuccinate stimulated net secretion of water, sodium, chloride and potassium and inhibited net absorption of glucose and bicarbonate. These changes in water and solute transport were partially reversed by administration of indomethacin (4 mg/kg/day orally for three days), which suggests that they are mediated in part by endogenous prostaglandins.

Alkaline Phosphatase

A radioimmunoassay for retinol-binding protein in serum and urine.

In this radioimmunoassay for human retinol-binding protein (RBP), sample (serum, diluted as much as 3600-fold; or urine, diluted or undiluted) or calibrant (purified RBP in phosphate buffer containing bovine serum albumin) is incubated with 125I-labeled RBP and rabbit anti-human RBP antiserum for 24 h before separation with second antibody/polyethylene glycol. The assay's sensitivity is 5 micrograms/L, its useful working range 10 to 200 micrograms/L. The between-batch CV is 12.5% at 12 micrograms/L, 7% at 120 micrograms/L. Results correlate well (r = 0.99) with those by radial immunodiffusion. The reference interval for RBP in serum of men is 39-75 mg/L (mean 57), significantly (p less than 0.01) broader than for women (29-66 mg/L; mean 48). The 2.5-97.5 centile interval for RBP in urine is from less than 0.5 to 12.2 micrograms per millimole of creatinine (median 5.8). RBP in urine is unstable below pH 5.0 at 37 degrees C.

Animals

Calibrant solutions for continuous-flow urate analysis: interference by formaldehyde.

The use of formaldehyde to preserve aqueous urate calibration solutions has been recommended since 1913, but it interferes in some commonly used methods. At a pH below 8.5 formaldehyde affects the rate of dialysis of urate in Technicon AutoAnalyzer systems. This effect has been studied by variation of the pH at which dialysis takes place. The interference is attributed to the formation of pH-dependent addition products between uric acid and formaldehyde, which have been examined by thin-layer chromatography and mass spectrometry. Recovery experiments on protein-containing solutions show that a purely aqueous urate calibrant solution is satisfactory for use in AutoAnalyzer systems.

Autoanalysis

Comparison of plasma disappearance and standard clearance techniques for measuring glomerular filtration rate in children with and without vesico-ureteric reflux.

The plasma disappearance rate, or slope clearance, after a single intravenous injection of 51Cr-EDTA was compared with simultaneously determined standard (UV/P) clearances of inulin, creatinine and 51Cr-EDTA in 4 healthy adults and 18 children with renal disease but no reflux. Slope clearance correlated well with standard inulin (r=0.99) and 51Cr-EDTA (r=0.97) clearances and was more accurate than creatinine clearance. Slope clearance x0.82 estimated standard 51Cr-EDTA clearance with +/- 12% accuracy in these subjects. In 18 children with vesico-ureteric reflux the correlations of the standard clearance methods with slope clearance were significantly reduced. Slope clearance may be measured with only two plasma samples and is recommended as the method of choice for determining glomerular filtration rate in children with gross reflux or impaired ability to empty their bladders.

Adolescent

Immunoelectrophoretic study of proteins in middle ear effusion. A study of secretory otitis media in children.

An immunoelectrophoretic study of the proteins of middle ear effusions in children with secretory otitis media is described. The findings support the view that the effusion is an exudate as a result of mucosal reaction. The protein content of the fluid appears to decrease as the condition becomes more chronic, and this seems to be enhanced by antibiotic treatment. In cases of bilateral disease, the ears may be in a quite different pathological phase, thus each ear should be treated independently.

Anti-Bacterial Agents