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Biomedical subjects

J K Lloyd

Publications and source records attributed to J K Lloyd.

At least 19 recordsLinked to original sources

Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.

Endothelial dysfunction is an early event in experimental studies of atherogenesis, preceding formation of plaques. We have devised a non-invasive method for testing endothelial function, to find out whether abnormalities are present in symptom-free children and young adults at high risk of atherosclerosis. With high-resolution ultrasound, we measured the diameter of the superficial femoral and brachial arteries at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilatation), and after sublingual glyceryl trinitrate (GTN; causing endothelium-independent dilatation) in 100 subjects--50 controls without vascular risk factors (aged 8-57 years), 20 cigarette smokers (aged 17-62 years), 10 children with familial hypercholesterolaemia (FH; aged 8-16 years), and 20 patients with established coronary artery disease (CAD). Adequate scans were obtained in all but 6 cases. Flow-mediated dilatation was observed in arteries from all control subjects. Dilatation was inversely related to baseline vessel diameter (r = -0.81, p < 0.0001); in arteries of 6.0 mm or less, mean dilatation was 10 (SE 2)%. In smokers, FH children, and adults with CAD, flow-mediated dilatation was much reduced or absent (p < 0.001 for comparison with each relevant control group). Dilatation in response to GTN was present in all groups. Endothelial dysfunction is present in children and adults with risk factors for atherosclerosis, such as smoking and hypercholesterolaemia, before anatomical evidence of plaque formation in the arteries studied. This may be an important early event in atherogenesis.

Adolescent

Disturbance in parent-child relationship following preterm delivery.

Increasing concern is expressed that the psychosocial development of preterm infants may be hindered by a disturbance of parental attitudes following the initial period of specialised care. Attitudes of parents of 17 preterm infants were compared with those of parents of 17 full-term infants at a single semi-structured interview six to 20 months after the birth. The groups of parents were matched for parity and did not differ in their social, ethnic and educational backgrounds. There was evidence of some disturbance in parent-child relationships in the preterm group, consisting of delays in maternal attachment to the child, negative maternal perception of the child compared with expectation of an 'average' baby, and persistent parental anxiety about leaving the child with a baby-sitter. In addition, two preterm children had been abused or neglected. Parental reaction to a preterm birth is discussed and the need for adequate support to be given to parents in the early period following the birth is stressed.

Anxiety

Surface binding and catabolism of low-density lipoprotein by circulating lymphocytes from patients with abetalipoproteinaemia, with observations on sterol synthesis in lymphocytes from one patient.

Surface binding of low-density lipoprotein (LDL), degradation of LDL protein and sterol synthesis were investigated in freshly isolated lymphocytes from normal and abetalipoproteinamic human subjects. LDL binding as a function of LDL concentration showed no evidence of the presence of high-affinity binding sites in fresh lymphocytes from either group of subjects. The rate of degradation of LDL protein by lymphocytes from the patients was no greater than that from the normal subjects and, in the fresh lymphocytes of the one patient studied, sterol synthesis was not increased. We conclude that the formation of LDL receptors and the synthesis of sterol in circulating lymphocytes are largely suppressed and that in normal subjects this may be due to the presence of some plasma constituent other than LDL, possibly the apoE protein. This conclusion is discussed in relation to the possible contribution of LDL receptors to the degradation of LDL protein in vivo.

Abetalipoproteinemia

Sterol balance in a patient with abetalipoproteinaemia.

Total-body cholesterol synthesis was measured in a woman with abetalipoproteinaemia and in a normal woman of similar age. The rate of synthesis of cholesterol was 15.4 +/- 4.1 mg/kg/day in the patient and 14.3 +/- 2.6 mg/kg/day in the control subject, indicating that cholesterol synthesis in the whole body is not increased in the complete absence of plasma low density lipoprotein.

Abetalipoproteinemia

Serum lecithin-cholesterol acyltransferase activity in children with familial hyperbetalipoproteinaemia.

Serum (non-fasting) was obtained from 71 healthy school children (12-14 years) and from 16 children with the heterozygous form of familial hyperbetalipoproteinaemia being treated by diet or ion-exchange resin. The activity of lecithin-cholesterol acyltransferase (EC 2.3.1.43) expressed as nmol cholesterol esterified/hour/ml serum did not change with increasing concentrations of unesterified cholesterol in the healthy children. In children with familial hyperbetalipoproteinaemia, lecithin-cholesterol acyltransferase activity was higher than in the healthy children and this activity increased with increasing concentrations of unesterified cholesterol.

Acyltransferases

Diagnosing familial hypercholesterolaemia in childhood by measuring serum cholesterol.

The serum cholesterol concentrations of 134 children aged 1-16 years who had at least one first-degree relative with presumed familial hypercholesterolaemia showed a bimodal distribution, and, using the maximum likelihood technique, two overlapping curves could be fitted. The mean value of the affected children (heterozygotes) was 8-9 mmol/l and that of the unaffected 4-9 mmol/l. The two curves intersected at 6-77 mmol/l, and at this point 5% of the unaffected children had values over 6-77 mmol/l and 3-5% of the heterozygotes had values under 6-77 mmol/l. If this cholesterol concentration is used as a cut-off point 4-25% of cases would be misdiagnosed.

Adolescent

Long-term management of abetalipoproteinaemia. Possible role for vitamin E.

Eight patients with abetalipoproteinaemia have been followed for 3-4 to 15-8 years. Management included dietary fat restriction and supplements of the fat-solublevitamins A, E, and K. In the 3 oldest patients serial studies of retinal and neurological function suggest that treatment with large doses of oral vitamin E may have delayed the development or progression of the neurological and retinal lesions.

Abetalipoproteinemia

Functional intestinal obstruction due to deficiency of argyrophil neurones in the myenteric plexus. Familial syndrome presenting with short small bowel, malrotation, and pyloric hypertrophy.

In 3 infants functional intestinal obstruction, associated with a short small intestine, malrotation, and pyloric hypertrophy, was shown to be due to failure of development of the argyrophil myenteric plexus, with the absence of ongoing peristalsis. 4 infants with similar clinical features have been described previously, and there is evidence for an autosomal recessive mode of inheritance of this syndrome.

Female

Screening for familial hyper-beta-lipoproteinaemia in children in hospital.

1510 plasma cholesterol estimations were made in 1391 children admitted to hospital as part of a biochemical profile. Babies under 1 year and children known to have familial hyperlipoproteinaemia were excluded. The mean concentration was 4-28 mmol/l +/- 1-04 (1 SD) (165-3 mg/100 ml +/- 38-6), and levels exceeded 5-93 mmol/l (229 mg/100 ml) in 68 children. Repeat estimations on 55 of these children showed 34 still to have values greater than 5-93 mmol/l and family studies were performed in 19 of these. In 8 children hypercholesterolaemia was secondary and no familial lipoprotein disorder was present. Familial hyper-beta-lipoproteinaemia (FH) was diagnosed in 3 children and in 2 of the families there was a history of early ischaemic heart disease. In 2 children the diagnosis was in doubt. In the remaining 6 children FH and secondary hyperlipoproteinaemia were excluded so the hypercholesterolaemia was presumably environmentally induced, possibly in association with polygenic inheritance. In the present state of knowledge screening of the childhood population for FH by means of plasma cholesterol determinations cannot be recommended. Studies of lipoproteins should, however, be made in children from families known to have FH or early coronary heart disease.

Cholesterol