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Biomedical subjects

N B Roberts

Publications and source records attributed to N B Roberts.

At least 73 records · Page 4Linked to original sources
PubMed1994

Silicon and aluminium and their inter-relationship in serum and urine after renal transplantation.

The present study was undertaken to establish the relationship between serum and urine silicon and improve renal function and examine whether the increased urinary excretion of aluminium observed after successful renal transplantation was associated with silicon. The changes in silicon and aluminium concentrations in serum and urine were measured in 15 patients for a period of up to 17 days following a first renal transplant. Serum silicon, unlike aluminium, progressively decreased with improving renal function and was significantly positively correlated with serum aluminium but not with the silicon excretion. The urine excretion of aluminium peaked between 4-8 days post-transplantation and was highly significantly positively correlated with urine silicon. The individual patient fractional excretion profiles of aluminium and silicon were variable but in general gave significant positive correlations suggesting that the elements may be cleared by the kidney through a common mechanism or as a chemical species, possibly an hydroxyaluminosilicate. If soluble silicon can chemically interact with aluminium in vivo it may, as in the biosphere, be important in the control of aluminium toxicity and eventual detoxification. Thus, elevated serum silicon concentrations may help to alleviate aluminium toxicity in end-stage renal disease and assist in the rapid clearance of aluminium seen after kidney transplantation.

Adult↗
PubMed1994

Seasonal variation in serum 25-hydroxy vitamin D3 does not affect 1,25-dihydroxy vitamin D.

The seasonal variation of serum 25-hydroxy vitamin D3 and 1,25-dihydroxy-vitamin D has been investigated. Blood was taken from 27 healthy volunteers, aged 21-44 years old at 3 monthly intervals over a period of 1 year. A scrolling monthly programme with 12 quarterly (3 month) time periods was developed. A summer associated increase in 25-hydroxy vitamin D3 was significantly correlated with but lagged behind by 2 months, the increase in recorded sunlight hours. However, four individuals showed no seasonal rise but maintained constant concentrations throughout the year within the established reference range. Serum 1,25-dihydroxy vitamin D showed marked intra-individual variability with no seasonal pattern although the highest concentration (180 pmol/L) was observed in the winter and no concentration greater than 108 pmol/L in the summer.

Adult↗
PubMed1993

Human pepsin 3b peptide map sequence analysis, genotype and hydrophobic nature.

Peptides from a Staphylococcus aureus (V8) proteinase digest of human pepsin 3b have been identified by amino acid sequence analysis. Only 137 out of 326 expected residues were detected from the C and N terminal regions of the molecule. Comparison with amino acid sequences derived from nucleotide analysis of three different pepsinogen A genes, identified 2 out of 4 possible substitutions. The presence of valine at position 30 and leucine at 291 indicates that the major pepsin component of gastric juice, pepsin 3b, corresponds to pepsinogen genotype PGA-3. Reversed-phase chromatography of native human pepsin 3b on C4 (300 A), C18 (300 A) or polymer (1000 A) columns was optimal on the C4 column and gradient elution with 2-propanol rather than acetonitrile. Denaturation of the protein in guanidinium hydrochloride, urea or high pH resulted in irreversible column retention. The marked hydrophobicity of denatured pepsin 3b may thus explain why the central segment of the protein was not revealed by peptide map analysis.

Amino Acid Sequence↗
PubMed1993

Assay of gastricsin and individual pepsins in human gastric juice.

AIMS: To develop and validate an analytical procedure for the quantitation of pepsins and gastricsin in human gastric juice and to assess its potential in a controlled gastric secretory study. METHODS: High performance ion-exchange chromatography was used to separate human pepsin 1, 3a, 3b, 3c and gastricsin from gastric juice. Computed chromatographic areas for each enzyme were quantified by relation to a known amount of a secondary standard porcine pepsin. The assay procedure was validated by recovery and analytical precision studies. Gastric secretions after pentagastrin and insulin stimulation from 10 patients with portal hypertension were used to assess the potential of the analytical procedure. RESULTS: The assay precision varied from 1.5 to 9.0% within batch and 7.5 to 18.1% between batch, with about 100% recoveries of porcine pepsin A from human gastric juice over the assay range 0.025-0.5 mg/ml. A fourfold increase in combined pepsin and gastricsin concentration was observed following pentagastrin and insulin stimulation. The mean percentage content of pepsins 3a, 3b, 3c, and 1 in non-stimulated gastric juice were 4%, 72%, 12% and 1.4%, respectively, and did not change significantly after gastric stimulation. An approximate doubling of the percentage of gastricsin (10% to 20%) relative to the pepsins was observed, however, after both insulin and pentagastrin stimulation. CONCLUSIONS: This procedure for quantifying individual human pepsins and gastricsin in gastric juice is simple and reliable. It may be of considerable importance in determining the mechanisms involved in the control and secretion of these digestive enzymes in man, including the effect of anti-ulcer drugs and our understanding of the pathophysiology of peptic ulcer disease.

Chromatography, Ion Exchange↗
PubMed1993

Resistance to recombinant human erythropoietin due to aluminium overload and its reversal by low dose desferrioxamine therapy.

Seventeen severely anaemic and transfusion-dependent haemodialysis patients with a haemoglobin less than 7 g/dl were treated with recombinant human erythropoietin (r-Hu-EPO). Aluminium toxicity was diagnosed by a positive desferrioxamine (DFO) test and bone biopsy. Seven out of eight patients without aluminium toxicity responded to r-Hu-EPO therapy. Similarly all patients with aluminium toxicity (n = 4) but pre-treated with standard dose of DFO prior to r-Hu-EPO therapy responded but none of the patients with untreated aluminium toxicity (n = 5) responded to r-Hu-EPO therapy. In order to achieve adequate response in these patients, r-Hu-EPO and DFO had to be given in combination. The dose of desferrioxamine used to reverse r-Hu-EPO resistance was less and also used for a short time. We therefore confirm r-Hu-EPO resistance owing to aluminium overload and report its successful and safe reversal with low dose DFO therapy.

Aluminum↗
PubMed1993

Measuring L-dopa in plasma and urine to monitor therapy of elderly patients with Parkinson disease treated with L-dopa and a dopa decarboxylase inhibitor.

We have established a method for measuring L-dopa in plasma and urine, including the metabolites dopamine and L-dopac, using separation by ion-pair reversed-phase HPLC and quantification with an electrochemical detector. The assay was applied to the therapeutic monitoring of elderly patients with established Parkinson disease being treated with L-dopa plus a dopa decarboxylase inhibitor. Plasma L-dopa was evaluated in relation to dosage and postdose sampling time in 71 outpatients with Parkinson disease. L-Dopa concentrations were greatest in the patients taking the highest dosages prescribed and decreased significantly with increasing time after postdose sampling. Comparison of plasma L-dopa concentrations with a published therapeutic range established by intravenous administration of L-dopa was helpful in assessing the suitability of each patient's drug dosage, assessing patients' compliance, and avoiding overdosage but was not useful in the overall clinical assessment of progression of disease or of the long-term therapeutic response. Urine measurements confirmed the plasma concentrations but showed no further advantage. The recommended time for sample collection is between 1.5 and 3 h after the first morning dose. Plasma is the preferred matrix but if blood sampling is difficult, particularly from elderly/infirm individuals, an untimed urine collection could be used.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Peptide maps of five human pepsin isoenzymes and other aspartic proteinases.

Peptide maps of five individual human pepsins were developed using reversed-phase high-performance liquid chromatography after protein digestion with either Staphylococcus aureus proteinase (V8) or alpha-chymotrypsin. Human pepsins 3a, 3b and 3c produced almost identical peptide maps suggestive of proteins with very similar amino acid sequences. The map for human pepsin 1 was similar to pepsin 3b (the most predominant human pepsin) but less than half the expected amount of each equivalent peptide fragment was generated, indicating that the actual mass of digested protein used was less than the dry weight measurement would suggest, probably as a result of carbohydrate attached to pepsin 1. Comparison of human pepsin 3b maps with other aspartic proteinases confirmed a significant homology with swine pepsin A but not with endothiapepsin. The alpha-chymotrypsin digests compared with V8 gave more complex peptide maps as a result of its broader bond cleavage specificities.

Animals↗
PubMed1992

Necropsy study of association between sudden death and cardiac enzymes.

AIMS: To determine if cardiac enzymes measured at necropsy could be used to predict early myocardial infarction. METHODS: Cardiac enzyme activities were measured in body fluids at necropsy. Coroners' necropsies were grouped by gross and microscopic findings into cases of definite myocardial infarction, cases with occlusive coronary artery atheroma but no identifiable myocardial infarction, and non-cardiac cases. Pericardial fluid, peripheral venous blood, and blood from the right atrium were collected. Total creatine phosphokinase, creatine phosphokinase isoenzymes, aspartate aminotransferase and hydroxybutarate dehydrogenase activities were measured and the results analysed by logistic regression. RESULTS: The values of creatine phosphokinase and its isoenzymes were raised in those who had died of cardiac disease and were most discriminatory. Cases of early myocardial infarction without evidence of infarction on routine histological examination could be identified from enzyme activities. CONCLUSIONS: Measurement of cardiac enzymes in blood and pericardial fluid at necropsy can provide valuable additional information in cases of sudden death as a result of myocardial ischaemia which have occurred before macroscopic or microscopic evidence of myocardial infarction.

Arteriosclerosis↗
PubMed1992

Concentrations of vitamins A, C and E in elderly patients with Parkinson's disease.

Concentrations of the naturally occurring antioxidant vitamins A, C and E were measured in 27 patients with Parkinson's disease and 16 age-matched control subjects, from a similarly disabled patient group. There was no significant difference in the serum concentrations of vitamins A and E in the two groups. Vitamin C was significantly higher (P < 0.05) in the Parkinson's disease group, however, the mean leucocyte vitamin C concentration in the control group was low (101 nmol/10(8) WBCS) compared to established data in healthy young individuals (119-301 nmol/10(8) WBCS). There was no correlation between the severity or duration of Parkinson's disease and concentrations of vitamins A, C and E. There is therefore no evidence from this study that a deficiency of these antioxidants contributes to the onset or progress of Parkinson's disease.

Aged↗
PubMed1992

Pyrophosphate in synovial fluid and urine and its relationship to urinary risk factors for stone disease.

Inorganic pyrophosphate (PPi) measurement in urine and synovial fluid has been established using the PPi-dependent phosphorylation of fructose-6-phosphate and subsequent reduction of dihydroxyacetone phosphate by NADH. The assay is linear up to 200 mumol/L, easy to perform and gives results comparable to more complex methods. Daily urinary output of PPi was independently related to both age (P = 0.0014) and sex (P = 0.0002). Men had higher values than women and older individuals excreted greater amounts. Male stone formers, younger than 45 years, had lower values than age matched male controls (P = 0.012). Younger female stone formers also tended to have lower values. In stone formers' urine significant and independent correlations were found of PPi excretion with urine volume (P = 0.004) and with phosphate excretion (P = 0.008). Oxalate excretion and that of other urine constituents and the degree of supersaturation with common stone-forming salts were not correlated with PPi. PPi excretion was markedly elevated in the urine of two patients with hypophosphatasia. The PPi concentration in synovial fluid from painful, swollen knee joints was elevated, but unrelated to the presence or absence of PPi or urate crystals.

Adolescent↗
PubMed1992

Urinary dopamine excretion in chronic renal disease.

We have measured unconjugated urinary dopamine and investigated its relationship to glomerular filtration rate in two groups of 22 patients with chronic renal failure matched for age and sex, one group with primary glomerular disease, the other with tubulo-interstitial disease. Urine dopamine excretion was similar in both glomerular and tubulo-interstitial disease groups, and correlated significantly with creatinine clearance. Although urinary protein excretion was significantly higher in glomerular disease, urinary sodium excretion, fractional sodium excretion, urine flow rate and free water clearance were similar in both groups and did not correlate with dopamine excretion. These results suggest that in patients with chronic renal disease, urinary dopamine excretion is mainly under the influence of the glomerular filtration rate, irrespective of the underlying pathology, and therefore interpretation of urinary dopamine excretion requires a knowledge of the patients' renal function.

Adult↗
PubMed1990

Silicon measurement in serum and urine by direct current plasma emission spectrometry.

Elemental silicon, present as soluble silicic acid in serum and urine, has been measured by direct current plasma emission spectrometry. The method is precise and accurate, yields a standard curve that is linear up to 1000 mumol/L, and requires only a simple dilution in 10 mL/L HNO3. No spectral or background interferences have been observed from serum or urine; the absolute detection limit for silicon was 0.5 mumol/L. Silicon concentrations in serum increase by up to 20-fold in patients with chronic renal failure on hemodialysis, an increase apparently related to dietary silicon intake. No relationship with aluminum was observed in hemodialysis patients, with or without aluminum toxicity. In the undialyzed patient with chronic renal failure, the concentrations of silicon in plasma increased with decreasing glomerular filtration rate. This increase may protect renal-failure patients from possible aluminum toxicity by promoting formation of the relatively inactive aluminosilicate complex. Silicon concentrations in urine of healthy individuals exceed their serum concentrations by 20- to 100-fold. Silicon excretion in patients with renal stones was not different from that in healthy controls and showed no relationship with calcium and (or) oxalate excretion.

Aluminum↗