Audrey S. Fosbrooke

A modified method for the preparation of methyl esters of a mixture of medium-chain and long-chain fatty acids: Application to the determination of serum triglyceride and non-esterified fatty acid composition and concentration by gas-liquid chromatography

A modified method for the preparation of methyl esters from triglycerides and NEFA-containing fatty acids, both medium- and long-chain, saturated and poly-unsaturated, is described (carbon chain length C8–C18). The addition of a suitable internal standard (triheptadecanoin or heptadecanoic acid) prior to methylation permits the quantification of serum triglycerides and NEFA in mixtures containing fatty acids saturated and polyunsaturated from C8–C18.

Plasma Lipids in Umbilical Cord Blood from Infants of Normal and Low Birth Weight

Plasma lipids were determined in the cord blood of 19 term, 16 preterm and 14 light-for-dates babies. Plasma triglyceride concentration was higher in the term than in the preterm group and was highest

Use of medium-chain triglyceride diets in children with malabsorption.

Medium-chain triglyceride (MCT) contains fatty acids with 8 or 10 carbon atoms and differs from long-chain triglyceride (LCT, containing fatty acids with 12 or more carbon atoms) in its water miscibility, its faster hydrolysis by pancreatic lipase, its ability to enter the intestinal mucosal cell unhydrolyzed and to undergo hydrolysis within the cell, and in the subsequent transport of its fatty acids, which are carried in an albumin complex in the portal blood stream. These properties form the basis for the use of MCT in situations in which the absorption of ordinary dietary fat (predominantly LCT) is impaired, and MCT diets have been described in the treatment of various malabsorptive states: in obstructive jaundice (Burke and Danks, 1966; Linscheer et al., 1966) and cystic fibrosis (Kuo and Huang, 1965; Anderson, 1968), where there is defective intraluminar digestion; in tropical sprue (Cancio and MenendezCorrada, 1964) and after intestinal resection (Zurier et al., 1966; Winawer et al., 1966; Burke and Anderson, 1967), where the absorptive area is decreased; in a-3-lipoproteinaemia (Isselbacher et al., 1964; Lloyd, 1968), where chylomicrons cannot be formed; and in intestinal lymphangiectasia (Holt, 1964; Holt, Hashim, and Van Itallie, 1965; Yssing, Jensen, and Jarnum, 1967; Poley et al., 1967), where chyle flow is obstructed. Because of its calorific value of 83 cal./g. (Kaunitz et al., 1958), MCT is likely to be particularly useful in the treatment of malabsorption in childhood when growth failure is often a problem. Encouraging results in this respect have been reported in cystic fibrosis (Kuo and Huang, 1965; Anderson, 1968), in liver disease (Burke and Danks, 1966), and after intestinal resection (Burke and Anderson, 1967). We describe our experience with MCT in the

A-β-lipoproteinaemia

Absence of 5-lipoprotein from the serum was reported by Salt, Wolff, Lloyd, Fosbrooke, Cameron, and Hubble (1960) in a child who had steatorrhoea and acanthocytosis. Simultaneously and independently, Lamy, Frezal, Polonovski, and Rey (1960) and Mabry, Di George, and Auerbach (1960) made similar observations. Three of the earlier cases of steatorrhoea with acanthocytosis, retinopathy, and disease of the central nervous system (Bassen and Kornzweig, 1950; Kornzweig and Bassen, 1957; Druez, 1959) have subsequently been shown to have a-p-lipoproteinaemia (Phillips, 1962; Schwartz, Rowland, Eder, Marks, Osserman, Anderson, and Hirschberg, 1961; Schwartz, Rowland, Eder, Marks, Osserman, Hirschberg, and Anderson, 1963; Druez, Lamy, Frezal, Polonovski, and Rey, 1961), and the case reported by Singer, Fisher, and Perlstein (1952) was later found to have a serum cholesterol level of 37 mg./100 ml. and a very low level of 5-globulin (Jampel and Falls, 1958) so that even in retrospect the diagnosis of a-3-lipoproteinaemia can be confidently made. Further cases have been reported by Friedman, Cohn, Zymaris, and Goldner (1960); Mier, Schwartz, and Boshes (1960); Wolff and Bauman (1961); Ways, Reed, and Hanahan (1961); Kuo and Bassett (1962); and Schwartz et al. (1963). This paper describes another example of this rare syndrome.

Metabolic studies and autonomic function in children with partial lipodystrophy

Studies of carbohydrate metabolism in 6 children with partial lipodystrophy (none of whom had evidence of renal disease) showed raised fasting serum insulin concentrations. In 4 of the children hyperinsulinaemia was found after oral glucose. Plasma glucose levels within the normal range in all tests indicated that the hyperinsulinaemia was due to insulin resistance. Plasma growth hormone concentration was normal in all children, and plasma cortisol concentration was normal in 5. Concentrations of plasma nonesterified fatty acid (NEFA), serum triglyceride, and cholesterol in fasting blood were normal. Adipose tissue from nondystrophic areas showed an increased proportion of palmitoleic acid. No abnormality of the autonomic nervous system was found. Treatment of 2 patients with propranolol did not improve their lipodystrophy. The metabolic abnormalities present at an early age of the disease show that partial lipodystrophy should not be regarded only as a cosmetic disorder.

Neutral lipids of plasma and adipose tissue in a-betalipo-proteinaemia

Abstract Plasma triglyceride concentrations were found to be very low in 4 children with a-betalipoproteinaemia; studies in one child after a meal containing 2 g/kg of corn oil showed no rise in plasma triglyceride in the post-absorptive state. However, evidence for absorption of the corn oil was provided by the finding of a rise in the proportion of linoleic acid in the plasma non-esterified fatty acid (NEFA) fraction during the first 6 h, and in cholesterol ester after 24 h. The fatty acid composition of adipose tissue triglyceride showed an increased proportion of palmitoleic acid, indicative of lipogenesis, and reduced linoleic acid, a consequence of impaired absorption; reduction in stearic acid was also found. The fatty acid pattern of plasma NEFA in general reflected that of the adipose tissue though in plasma NEFA normal levels of linoleic acid were found in the two patients receiving supplementary corn oil. In all children linoleic acid in cholesterol ester was very low. Plasma post-heparin lipolytic activity was grossly reduced in the three children in whom it was estimated.

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.

Improved precision for the autoanalyser determination of serum cholesterol.

Abstract Modifications are described for the Technicon N 24A method1 for the analysis of serum cholesterol by the AutoAnalyser. The precision is thereby improved so that over a period of about 6 months the coefficient of variation was 1.75% (control serum concentration 200 mg/100 ml, 1 SD = 3.5). The use of preparative thin-layer chromatography allows for the separate determination of free and ester fractions when required.

Familial hypo-β-lipoproteinaemia

A 2-year-old boy investigated because of small stature, had low serum levels of cholesterol (74 mg/100 ml) and β-lipoprotein cholesterol (20 mg/100 ml). Faecal fat, jejunal biopsy, red cell morphology, and plasma growth hormone and thyroxine were normal, and it was concluded that the small stature was hereditary. A family study showed a similar lipoprotein abnormality in the patients mother; her serum cholesterol was 83 mg/100 ml and β-lipoprotein cholesterol 34 mg/100 ml. Analysis of the β-lipoprotein fraction in both child and mother showed it to have an abnormal lipid composition; the cholesterol/phospholipid ratio was 1·0 and 0·8, respectively (normal 1·7), and within the phospholipid components the proportion of sphingomyelin was markedly reduced (11% and 5%, normal 30%). These findings differ from previous reports that the composition of β-lipoprotein is normal. Familial hypo-β-lipoproteinaemia has been shown to be inherited as an autosomal dominant, and our findings are in agreement. Although a few individuals with this condition have been reported to have some of the features associated with a-β-lipoproteinaemia, neither our patient nor his mother had any gastrointestinal, haematological, or neurological abnormalities.

Carbohydrate-induced Hypertriglyceridaemia in a Child

Carbohydrate-induced hypertriglyceridaemia is described in a 12-year-old boy, whose father died of premature coronary heart disease. Serum triglyceride and pre-fl-lipoprotein concentrations were high on a self-selected diet and were reduced to normal by a low carbohydrate diet. It proved difficult to maintain triglyceride levels by diet at home, but the addition of clofibrate improved the control. Clearing of lipid from the serum after an oral fat load was delayed when the fasting serum triglyceride was high, but became normal after the serum triglyceride had been reduced by diet. An oral glucose load showed impairment of glucose tolerance. Insulin resistance was suggested by a small decrease in plasma glucose, with a normal increase in serum insulin, after intravenous tolbutamide. Serum triglyceride and pre-f-lipoprotein concentrations increased after oral glucose. Observations in two other children with diabetic glucose tolerance curves suggested that the increase in serum triglyceride after oral glucose was related to the insulin response rather than to the degree of hyperglycaemia.