Biomedical subjects
Publications and source records attributed to R S Ersser.
Automated cation exchange microcolumn chromatography of haemoglobins has been modified for the analysis of haemoglobin A2. It provides the quantitative data of sufficient precision and specificity for the investigation of potential heterozygotes for beta-thalassaemia. Results have been compared with an established method of electrophoresis followed by densitometry of the eluted bands.
Amino acid analysers have been used for the quantitative investigation of amino acids in physiological fluids for over 30 years. Advances in technology have resulted in a steady decrease in analysis time and detection limits of the cation-exchange chromatography, followed by ninhydrin detection, used by the original instruments. The introduction of pre-column derivatisation and alternative HPLC techniques offers new opportunities for advancement. The analytical characteristics, principles, merits and limitations of both techniques are discussed, and their suitability for clinical purposes assessed. Practical considerations are emphasised and the influence of choice of chemistry and instrument design on the resolution and quality of quantitative data is highlighted.
The suitability of pre-column derivatization with phenylisothiocyanate followed by high-performance liquid chromatography was investigated as a means of analyzing free amino acids in plasma and other physiological fluids. A comparison was made between this method and a conventional ion-exchange method. The correlation coefficient for all the amino acids tested was greater than 0.9, except for proline and tryptophan. Various forms of sample preparation were tried for plasma and amniotic fluid; it was finally decided that protein precipitation with acetonitrile was most suitable. Ultrafiltration was used for cerebrospinal fluid preparation while urine was treated the same as a standard mixture. The retention times relative to the internal standard (nor-leucine) are given for over 90 compounds. Some of these were chromatographed underivatized because they are known to be present in some physiological fluids and absorb at 254 nm because of their aromaticity. The imprecision for this method compared favourably with the standard ion-exchange method although each had specific amino acids for which the imprecision was poor. The technique is suitable for the same routine clinical analysis purposes as high-resolution ion-exchange chromatography. It also offers the advantages of speed of analysis, sensitivity and equipment versatility over the conventional ion-exchange methods.
An unusual form of diarrhoea is reported that was relieved when breast feeding was stopped. Chromatography to estimate sugars in the faeces should be performed for all infants with unexplained diarrhoea before changes are made in the diet.
A thorough investigation of the behavior of organic acids on the Bio-Rad Aminex cation exchange resin was prompted by both the limitations of, and a number of inexplicable inconsistencies found in, previously published papers using an identical system. In order to stabilise the elution order of various acids it was necessary to analyse samples at a higher temperature than previously recommended. This temperature (50 degrees C) decreased the retention times of all acids permitting the analysis of both aromatic and aliphatic acids within the same 45-min run. Preparation of an acidic fraction of biological fluids improved specificity, allowed direct comparison of urine and plasma profiles and by control of the conditions interference by urate could be substantially reduced. Retention data are given for more than 90 acidic metabolites including nearly 40 of clinical significance and a number derived from diet and drug therapy.
Rapid, quantitative, chromatographic separations of mixtures of human haemoglobins have been performed on short (5-20 mm) columns of packing material. The desirable characteristics of suitable column packing materials are illustrated and discussed. Simple, inexpensive, manually operated equipment can be used for the analysis, since the specifically designed midget columns generate little back pressure (10-30 lb/in2) when eluted at constant flow rates up to 2 mL/min. Cation exchange chromatography on bonded silicas has been used for the detection of pathological haemoglobinopathies. Separations similar to the HPLC procedures are possible with the correct selection of buffer composition. It also compares favourably with the methods in common clinical use employing electrophoresis on cellulose acetate. Both ion-exchange and affinity methods for the estimation of glycated haemoglobins have been developed and are compared.
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A total of 795 382 infants born in north London was screened for phenylketonuria using the Guthrie test between October 1969 and December 1978. During this period it became recognised that phenylketonuria is not a single disease entity but one that encompasses a number of disorders of differing clinical and biochemical severity. The overall incidence of persistent hyperphenylalaninaemia was of the order of 7 per 100 000 births (or 1 in 15 000) and all the early treated patients made normal developmental progress. During the study there was an appreciable fall in the incidence of uncomplicated transient hyperphenylalaninaemia with or without tyrosinaemia. This reduction coincided with the change in infant feeding practice in the UK which led to lower intakes of protein and phenylalanine. It was concluded that any infant found to have a persistent blood phenylalanine concentration of 240 mumol/1 (4 mg/100 ml) or greater should be followed closely.
A systematic identification scheme, based on improved paper and thin-layer chromatography, acidic and enzymatic hydrolysis, and the reaction of carbohydrates with several location reagents, has been applied to the analysis of oligosaccharides present in the urine and faeces of sick children and the diets they are fed. The identity and origin of these oligosaccharides is described and their relevance to the diagnosis and treatment of children with suspected disorders of carbohydrate metabolism is discussed.
The Guthrie test was used to measure blood methionine concentrations in 670 764 neonates during the period from May 1970 to December 1977. Raised values (greater than 4 mg/100 ml; 268 mumol/l) were found in 147 babies (6--14 days old) and 55 of these still had raised values when retested 2--6 weeks later. 48 infants had transient hypermethioninaemia of at least 3 weeks' duration, one had a more persistent form associated with abnormal liver function tests, 3 had different forms of homocystinuria, and one infant, who was asymptomatic at the time of detection, had hypermethioninaemia associated with a rapidly fatal form of tyrosinamiea (tyrosinosis). Two infants could not be followed up. Transient hypermethioninaemia has not been detected in this laboratory since 1975. There was a greatly reduced incidence of transient hypermethioninaemia in girls after 1972 and in boys after 1975; this may have been due to recent changes in infant practices in the UK. Homocystinuria was last detected in this laboratory in 1972; the apparent change in incidence is significant (P less than 0.05) and suggests that the diagnostic value of this screening procedure should be reassessed.
Simple and rapid thin-layer chromatographic methods have been used to investigate the catecholamine metabolites present in the urine of sick children. A semi-quantitative method for 4-hydroxy-3-methoxy-mandelic acid (HMMA) has been devised and compared with the quantitative spectrophotometric procedure. The methods have been performed on both normal subjects and children with catecholamine-secreting tumours, without dietary restriction, and have led to a 50% reduction in the number of samples requiring laborious quantitative determination of HMMA excretion.
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O-Hydroxyhippuric acid has been identified in the urine of a number of sick children who were not receiving salicylate-containing drugs. Characterisation was effected by thin-layer and gas-liquid chromatography and by gas-liquid chromatography-mass spectrometry. An association between gastro-intestinal dysfunction and the excretion of o-hydroxyhippuric acid was observed in approximately 50% of the patients who excreted this substance.
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