Barbara E. Clayton

Effect of smoking, alcohol, and other factors on the selenium status of a healthy population.

In a study of selenium status in 391 apparently healthy subjects resident in the south of England statistical examination of the data showed a significant effect with regard to age, smoking, alcohol, and oral contraceptives. The most important of these factors seems to be a combination of alcohol and smoking habits in men over 30. Reference ranges have been established for glutathione peroxidase activities and the concentrations of selenium in whole blood plasma and erythrocytes.

Hormonal changes in thalassaemia major.

Patients with severe thalassaemia major suffer endocrine and other abnormalities before their eventual death from iron overload due to repeated blood transfusions. The endocrine status of 31 thalassaemic patients aged 2-5 to 23 years was investigated. Exact data were available on the rate and duration of blood transfusion in all of them and in many the liver iron concentration was also known. Although the patients were euthyroid, the mean serum thyroxine level was significantly lower, and the mean thyrotrophic hormone level significantly higher, compared with the values found in normal children. Forty oral glucose tolerance tests with simultaneous insulin levels were performed in 19 children, of whom 5 developed symptomatic diabetes and one had impaired tolerance. Previous tests on all 6 patients were available and some showed raised insulin levels possibly due to insulin resistance. 2 patients had clinical hypoparathyroidism and are described. The parathyroid hormone levels determined by radioimmunoassay in 25 patients were below the mean for the age group in all and outside the reference range in 16. Nonfasting plasma calcium levels were not reduced. Puberty was delayed in some patients. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measured in urine from 7 girls and 5 boys showed considerable variation. In the boys there was an overall tendency for FSH and LH excretion to be low with regard to age, but with respect to puberty rating FSH exretions were normal or low and LH normal or raised.The girls showed a tendency for LH but not FSH excretion to be raised in relation to puberty rating. The severity of the endocrine changes was related to the degree of iron loading and is discussed in relation to previous work in which the iron loading has rarely been accurately indicated nor parathyroid status assessed.

Selenium and vitamin E status of healthy and institutionalized elderly subjects: analysis of plasma, erythrocytes and platelets.

Levels of selenium in whole blood, plasma, erythrocytes and platelets, glutathione peroxidase (EC 1.11.1.9; GSH-Px) activity in erythrocytes and platelets and vitamin E, low-density-lipoprotein (LDL)-cholesterol and vitamin E: LDL cholesterol in plasma were measured in seventy-five healthy subjects aged less than 65 years and twenty-eight healthy and twenty-three institutionalized elderly people aged greater than 65 years. Healthy elderly subjects had significantly lower levels of Se in whole blood and plasma when compared with younger subjects. Other measurements of Se status were not significantly different. In the healthy subjects plasma levels of vitamin E and LDL-cholesterol increased with age to 60 years and decreased above 80 years. Vitamin E: LDL cholesterol values were not affected by age. Measurements of Se and vitamin E status in the institutionalized elderly compared with the healthy elderly were all reduced with the exception of platelet Se levels and erythrocyte GSH-Px activity. Ageing per se had minimal effect on Se and vitamin E status but intercurrent illness and decreased food intake can lead to reduced levels in the elderly.

Nitrogen balance studies in apparently healthy elderly people and those who are housebound.

Metabolic balance studies (5 d) for nitrogen were carried out in twenty-four apparently healthy elderly people (age 69.7-85.6 years) and a heterogeneous group of twenty housebound elderly people (age 69.9-85.1 years) with chronic diseases. During the study all subjects ate self-selected diets, lived in their own homes and continued their normal daily activities. Seven of the housebound received meals-on-wheels 5 d/week. Healthy men and women had mean metabolizable energy intakes of 8.7 and 6.6 MJ/d respectively compared with 6.3 and 4.8 MJ/d in the housebound. The average energy content of the meals-on-wheels as delivered was 2.4 MJ per meal, of which 2.1 MJ were consumed. The healthy men and women had average daily protein intakes of 69.4 and 59.7 g respectively compared with 46.3 and 39.1 g in the housebound. Meals-on-wheels as supplied provided 19.4 g protein per meal, of which 16.2 g were consumed. Healthy subjects were in equilibrium for N balance (0 mmol/d) with a daily intake of 733 mmol, which was equivalent to 11.04 mmol N (0.97 g mixed protein)/kg body-weight per d. Housebound individuals were in negative N balance (-95 mmol/d) with an intake of 475 mmol/d, corresponding to 7.59 mmol N (0.67 g mixed protein)/kg body-weight per d. We were unable to determine in the present study whether the negative N balance observed in the housebound people was due to the relatively low N intake or the underlying disease condition.

Neonatal mass screening for metabolic disorders

The present situation of neonatal mass screening for metabolic disorders in eleven European countries is presented. The only disease screened for on a population wide basis in almost all countries is phenylketonuria. Screening for congenital hypothyroidism has been started in most countries or is under active consideration. A priority list of disorders that should be screened for routinely in all newborns comprises congenital hypothyroidism, hyperphenylalaninaemia, galactosaemia and maple syrup urine disease. Other disorders, like adrenogenital syndrome, cystic fibrosis. Duchennes muscular dystrophy, histidinaemia, or tyrosinaemia cannot be recommended for mass screening at present because of an unsatisfactory test procedure or lack of effective treatment.

An appraisal of the analytical significance of tooth-lead measurements as possible indices of environmental exposure of children to lead.

The analysis for lead of whole crowns from deciduous incisors has been used as an index of the cumulative exposure to lead of children during the prenatal period and until the time of shedding the tooth. The lead was determined by solvent extraction followed by atomic absorption, and strict analytical quality control was employed. The concentrations of lead in pairs of central and lateral incisors from children revealed unexpectedly large differences for some individuals.

Histidinaemia: Study of Relation Between Clinical and Biological Findings in 7 Subjects

Seven subjects with raised plasma histidine and low skin histidase levels (histidinaemia) are described: 4 were severely retarded, 2 showing in addition features of an early infantile psychosis (autism); 3 were of normal intelligence. There were no biochemical differences between the two groups. In view of these findings and a study of patients reported in the literature, attention is drawn to the difficulty in making a decision about treatment of a neonate detected by screening and shown to have the biochemical features of histidinaemia. The natural history of the condition is further examined, particularly the question of deterioration at time of seizures or infection.

Inherited disorders of 3-methylcrotonyl CoA carboxylation.

The clinical course of 4 patients who had reduced activities of 3-methylcrotonyl CoA carboxylase (also called 3-methylcrotonylglycinuria) is described. Two children presented with a metabolic acidosis, one in the neonatal period and the other with episodes of acidosis that started in the second year of life. In the other 2 children neurological symptoms were prominent, one having infantile spasms and the other developmental regression with a skin rash and alopecia. Three of the children responded well to oral biotin and dietary protein restriction but the fourth, despite a biochemical response to biotin, has a severe neurological handicap. The clinical presentation of inborn errors of 3-methylcrotonyl CoA carboxylase is variable. Metabolic acidosis may not be conspicuous and instead neurological features may predominate.

Pyridoxol metabolism in vitamin B6-responsive convulsions of early infancy.

As there is uncertainty about the nature of the metabolic defect in vitamin B6-responsive convulsion, certain aspects of pyridoxol metabolism were studied in 3 patients who were believed on clinical grounds to have the condition. The findings were compared with those in healthy children and adults, and in children with mental handicap. The magnitude of the initial rise and the subsequent fall in plasma pyridoxal phosphate (PALP) concentrations after a load of pyridoxol suggested that the vitamin B6-responsive patients were able to synthesise PALP normally but were unable to maintain the prolonged high levels normally found in plasma. The urinary excretion of 4-pyridoxic acid was within normal limits, but the excretion of pyridoxol after the load was raised. It is suggested that there may be an instability of the PALP-albumin complex in this condition. Some of the biochemical features were also observed in an infant presenting with convulsions soon after birth but without evidence of clinical B6-dependency.

Selenium balance studies in apparently healthy and housebound elderly people eating self-selected diets.

1. Metabolic balance studies (5 d) for Se were conducted in twenty-four apparently healthy elderly people (age 69.6-85.4 years), and twenty housebound subjects (age 69.9-85.1 years) with chronic disease. During the study the subjects lived in their own homes, ate self-selected diets and continued their normal daily activities. 2. Geometric mean daily dietary intakes of the two groups were significantly different (P less than 0.01), being 819 (range 310-1631) nmol for the healthy and 475 (range 233-1136) nmol for the housebound elderly. 3. Daily intake of Se significantly correlated with balance in both groups. Solution of the regression equations gave theoretical daily requirements of 447 nmol for the healthy and 419 nmol for the housebound subjects. The healthy elderly were in positive balance of 148 nmol/d for Se and the housebound were in equilibrium with an overall mean retention of 43 nmol/d. 4. Mean levels of Se in blood fractions for the healthy and housebound subjects were significantly different, being 1.65 and 1.40 mumol/l whole blood, 1.45 and 1.21 mumol/l plasma and 5.72 and 5.30 nmol/g haemoglobin in erythrocytes respectively. There was no difference in the whole-blood glutathione peroxidase (EC 1.11.1.9) activities between the two groups. 5. There were clear differences in Se status between the two groups of elderly people. The cause of the positive balance in the healthy subjects remains unexplained.