Lipoprotein alterations in children with bacterial meningitis

Abnormalities in serum lipids, including hypertriglycerideinia, are common during infectious disorders. However, the lipoprotein pattern during infections, particularly in children, has been investigated to only a limited extent. We have monitored alterations in serum lipoproteins in eight children with a severe baclcrial infcction (meningitis) by a quantitating method measuring cholesterol and triglyccrides in each major class. The levels of triglyccrides in serum and in low-density lipoproteins were markedly elevated during the infection, whereas the amount of cholesterol in high-density lipoprotcins was decreased. The cholesterol to triglyceride ratio was decreased in low-, as well as in high-density lipoproteins. These lipoprotein abnormalities may, at least in part, be explained by a depressed lipolytic activity of lipoprotein lipasc, the key enzyme for removal of triglycerides in man. Serum triglycerides and the levels of cholesterol in high-density lipoproteins, as well as the ratio between these parameters, may be used as indicators of inflammatory activity.     

Lipoprotein alterations and plasma lipoprotein lipase reduction in familial hemophagocytic lymphohistiocytosis.

Serum lipid abnormalities are common in familial hemophagocytic lymphohistocytosis (FHL), a disorder also characterized by fever, hepatosplenomegaly, pancytopenia and a prominent lymphohistiocytic accumulation in the mononuclear phagocyte system. The lipoprotein pattern in nine children with FHL was studied with a quantitative method measuring cholesterol and triglycerides in each major class of lipoproteins. Triglycerides were markedly elevated during active FHL in serum, very low density lipoproteins, and low density lipoproteins. Cholesterol was increased in very low density lipoproteins whereas both triglycerides and cholesterol were extremely low in high density lipoproteins. These lipoprotein abnormalities, reversible on successful therapy, are compatible with a depressed lipolytic activity. Post-heparin levels of lipoprotein lipase and hepatic lipase in plasma were studied in four children and found to be markedly low during active FHL. We suggest that inflammatory cytokines, which may strongly suppress lipoprotein lipase activity, can be important mediators in the pathophysiology of FHL and that they may participate in the development of the lipid abnormalities.     

Lipoprotein Alterations and Plasma Lipoprotein Lipase Reduction in Familial Hemophagocytic Lymphohistiocytosis

ABSTRACT. Serum lipid abnormalities are common in familial hemophagocytic lymphohistocytosis (FHL), a disorder also characterized by fever, hepatosplenomegaly, pancytopenia and a prominent lymphohistiocytic accumulation in the mononuclear phagocyte system. The lipoprotein pattern in nine children with FHL was studied with a quantitative method measuring cholesterol and triglycerides in each major class of lipoproteins. Triglycerides were markedly elevated during active FHL in serum, very low density lipoproteins, and low density lipoproteins. Cholesterol was increased in very low density lipoproteins whereas both triglycerides and cholesterol were extremely low in high density lipoproteins. These lipoprotein abnormalities, reversible on successful therapy, are compatible with a depressed lipolytic activity. Post-heparin levels of lipoprotein lipase and hepatic lipase in plasma were studied in four children and found to be markedly low during active FHL. We suggest that inflammatory cytokines, which may strongly suppress lipoprotein lipase activity, can be important mediators in the pathophysiology of FHL and that they may participate in the development of the lipid abnormalities.     

Effect of Growth Hormone on Lipoprotein Metabolism in Male Pituitary Dwarfs: Changes in Lipoprotein Lipase Activity and Cholesterol Level in HDL Subfractions

To determine the effect of a chronic therapeutic dose (0.24 IU/kg/week) of growth hormone on the cholesterol concentration in serum lipoproteins and postheparin plasma lipase activities in previously untreated children with idiopathic growth hormone deficiency, seven male patients under 10 years of age were studied before and three months after the initiation of growth hormone therapy. Lipase activity was measured by an immunochemical method. The cholesterol concentration in high-density lipoprotein subfractions was determined, using a micromethod for ultracentrifugation. Serum total cholesterol and triglyceride levels did not change significantly during treatment, while the high-density lipoprotein cholesterol level decreased significantly after treatment to 79% of the baseline level, with an equal decrease of cholesterol concentration in both high-density lipoprotein₂ and ₃. Lipoprotein lipase, but not hepatic triglyceride lipase, activity decreased significantly after treatment. These were not associated with changes in either thyroid status as determined by serum triiodothyronine levels or insulin responsiveness after oral glucose challenge, suggesting that these changes may be induced by a direct action of growth hormone.     

Should children with infection be tested for lipid,lipoprotein and apolipoprotein?

The lipid profile is known to alter in patients with infection, but there has not been a study of the apolipoprotein levels in serum of otherwise healthy children during infection. Lipids, lipoproteins, apolipoproteins A-l and B and lipoprotein (a) were evaluated prospectively in 31 consecutive children, aged4–15 years, who were admitted to the hospital with bacterial pharyngitis. The degree of dyslipidemia associated with bacterial pharyngitis was assessed using each child as his/her own control and by comparison with 79 healthy children who had not had an infection during the past 3 months. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-l and apolipoprotein B levels were significantly decreased during the symptomatic phase of the disease, whereas the serum triglyceride level was slightly elevated. Serum lipoprotein (a) concentration did not change significantly. In conclusion, it is suggested that serum lipids, lipoproteins and apolipoproteins should not be assessed during infection because of the possible transient changes of these parameters during infection or inflammation.     

Changes in serum lipids and lipoproteins in epileptic children treated with anticonvulsants

Objective: To assess the effect of long-term treatment of phenobarbital, carbamazepine and sodium valproate on serum lipids and lipoproteins in epileptic children.
Methodology: One hundred and fourteen (55 male, 59 female) children and adolescents suffering from various types of epilepsy who received different antiepileptic drugs were studied. The patients were subdivided into three groups according to their therapy: (i) carbamazepine (35 patients); (ii) phenobarbital (34 patients); and (iii) sodium valproate (45 patients). One-hundred healthy sex- and age-matched children served as controls. Lipids and lipoprotein profile were evaluated before the beginning of the anticonvulsant therapy and after at least 2.5 years. In the patients receiving phenobarbital, we re-evaluated 12 children (seven male, five female) at the end of therapy.
Results: The children receiving phenobarbital showed high levels of serum total cholesterol and low-density lipoprotein (LDL) cholesterol and low levels of triglycerides, while children treated with carbamazepine had high levels of total cholesterol, triglycerides, LDL and high-density lipoprotein (HDL) cholesterol. Children treated with valproate had low triglycerides and LDL cholesterol levels with high levels of HDL cholesterol. The patients treated with phenobarbital showed a normalization of all parameters after the end of therapy.
Conclusions: Anticonvulsant drugs significantly modify serum lipids and lipoproteins in epileptic children. The changes due to phenobarbital seem to be transient.     

Serum lipids and apolipoproteins in Spanish children and adolescents: a 5 year follow-up

This study was designed to assess "tracking" of serum lipids and apolipoproteins in three age groups of Spanish children over a 5 year period. A total of 84 6-year-old, 89 10-year-old and 64 14-year-old children were evaluated in 1989 (with measurement of serum total cholesterol, triglycerides, lipoproteins and apolipoproteins A1 and B), and re-evaluated in 1994. Correlation coefficients between initial and final lipid and apolipoprotein values were as follows: total cholesterol, 0.66; low-density lipoprotein (LDL) cholesterol, 0.65; high-density lipoprotein (HDL) cholesterol, 0.61; triglycerides, 0.61; apolipoprotein A1, 0.60; apolipoprotein B, 0.66. When age groups were analysed separately, children who were 14 years old at the beginning of the study showed higher correlation coefficients, particularly for total cholesterol and LDL cholesterol (> 0.7 in both cases). More than 70%, of children who were in the top quintile of total, LDL or HDL cholesterol as well as apolipoprotein A1 or B in 1989 remained in the top quintile 5 years later.     

The effects of long-term anticonvulsive treatment on serum lipid profile

Serum lipids were determined in 10 untreated patients with recently diagnosed epilepsy, 21 patients treated with carbamazepine (CBZ), 10 patients treated with valproate (VPA) and in 15 healthy children. In relation to the controls, patients receiving CBZ showed increased serum high-density lipoprotein cholesterol (HDLc), apolipoprotein A (Apo-A) and apolipoprotein B (Apo-B). Patients receiving VPA showed increased Apo-B levels. There were no significant differences in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDLc) or very low-density lipoprotein cholesterol (VLDLc) between all groups. The changes in lipid metabolism may be associated with the induction of liver enzymes during anti-epileptic drug metabolism. The CBZ-induced change in serum lipid levels was considered to be a possible factor against atherosclerosis and coronary heart disease in epileptic patients.     

Association of low-density lipoprotein particle size distribution and cardiovascular risk factors in children

AIM: The objective of this study was to investigate whether the presence of small, dense lipoproteins, which are thought to be related to the metabolic syndrome caused by insulin resistance, can be predicted by routine serum lipid profiling. METHODS: The relationship between low-density lipoprotein (LDL) particle size and serum lipid levels was analysed in 284 school children (148 boys and 136 girls), aged 7 to 13 y old. LDL particle size was determined by gradient gel electrophoresis. RESULTS: The LDL particle diameter was significantly correlated with the serum levels of high-density lipoprotein cholesterol (HDL-C) (r = - 0.437, p < 0.001) and triglycerides (TG) (r = -0.432, p < 0.001), and with the atherogenic index (AI) [total cholesterol/ HDL-C] (r = -0.450, p < 0.001), while only weak correlations were observed with the serum levels of total cholesterol, apolipoprotein Al and apolipoprotein B. No significant relationship was observed between LDL particle diameter and the serum LDL-C level. CONCLUSION: The presence of small, dense LDL as a metabolic marker of lifestyle-related diseases in children seems to be reflected by a serum lipid profile characterized by an elevation in TG, a reduction in HDL-C, and a raised AI.     

Levels of lipoprotein(a) and plasma lipids in Spanish children aged from 4 to 18 years

Increased plasma lipoprotein(a)-Lp(a)-levels are linked to a high risk of cardiovascular disease unrelated to other lipoproteins. It seems that Lp(a) values in childhood remain unaltered up to adulthood. In a randomly chosen population of 1970 children, aged from 4 to 18 years and living in a Spanish community, the following serum parameters were studied: total cholesterol, total triglycerides, Lp(a), high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. Mean Lp(a) serum values were 15.0 ± 14.7mg dl^-1. No differences were seen between either sex in the first years of childhood. Of the studied children, 15.1% presented Lp(a) concentrations above 30 mg dl^-1. A correlation between Lp(a) and total cholesterol concentrations, which disappeared when low-density lipoprotein cholesterol concentrations were corrected according to cholesterol present in Lp(a), was observed.     

Serum lipid alterations in acute lymphoblastic leukemia of childhood

Epidemiologic studies have indicated a relationship between serum lipids and cancer, and it is possible that lipid abnormalities are involved in the mechanism of oncogenesis. This study was performed to investigate serum lipid alterations in patients with acute lymphoblastic leukemia (ALL) at diagnosis and during remission of the disease. Plasma lipids and lipoproteins were measured at diagnosis, prior to the administration of induction treatment, and every 2 months for the first 12 months of the maintenance phase of chemotherapy in 64 patients with ALL. Nearly all patients demonstrated a predictable pattern of serum lipid alterations that consisted of extremely low levels of high-density lipoprotein cholesterol, elevated triglycerides, and elevated low-density lipoprotein cholesterol. Patients studied again during remission demonstrated a return to normal values, and the difference was statistically significant. The results suggest that at diagnosis of ALL an abnormality in lipid metabolism is present, which is reversed during remission.     

Lipoprotein changes in small-for-gestational-age infants fed nucleotide-supplemented milk formula

Morillas J, Moltó L, Robles R, Gil A, Sánchez-Pozo A. Lipoprotein changes in small-for-gestational-age infants fed nucleotide-supplemented milk formula. Acta Prediatr 1994;83:481–5. Stockholm. ISSN 0803–5253
We determined the effect of supplementing milk formula with nucleotides on plasma lipoproteins in small-for-gestational-age infants: 21 infants were fed a nucleotide-supplemented formula and 20 infants were fed the same nucleotide-free formula. On days 0, 3 and 7 after birth, major plasma lipoprotein fractions were analyzed for apolipoprotein and lipid composition. Compared with the control group, the group receiving nucleotides had increased total apoprotein concentrations in all lipoproteins as well as increased apo A-I in high-density lipoproteins and very low-density lipoproteins, and apo B-100 in very low-density lipoproteins and low-density lipoproteins. Very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol and very low-density lipoprotein triglycerides increased in parallel to the changes in apoproteins. The cholesterol ester to unesterified cholesterol ratio was increased in low-density lipoproteins and, particularly, in high-density lipoproteins. These data support the hypothesis that lipoprotein metabolism in small-for-gestational-age infants is affected by dietary nucleotide supplementation, enhancing lipoprotein synthesis or secretion. Cholesterol esterification capacity paralleled the apo A-I increase, in agreement with the co-factor role of apo A-I on lecithin: cholesterol acyltransferase.     

Impact of increasing adiposity in hyperlipidemic children

Despite lifestyle management, children with high-risk hyperlipidemias may become overweight, and this may further adversely impact their lipid profile. Regression analysis was used to determine changes over time in adiposity and their association with lipid profiles and other risk factors for hyperlipidemic children followed in a lipid disorder clinic. 184 patients were included. Median age at presentation was 7 years (2-17 years), and median duration of follow-up was 9 years (5-20 years). Mean initial total cholesterol was 6.9+/-1.6 mmol/L, low-density lipoproteins were 5.2+/-1.7 mmol/L, high-density lipoproteins were 1.2 +/- 0.4 mmol/L, triglycerides were 1.1+/-0.8 mmol/L, and body mass index z score was +0.4+/-1.0. A significant increase in body mass index z score (+0.032/year, P< .001) was observed. There was an associated significant increase in total cholesterol and triglyceride levels and decrease in high-density lipoprotein levels over time. Worsening adiposity is prevalent in hyperlipidemic children and adversely affects their lipid profiles and cardiovascular risk.     

Serum Fructosamine and Lipid Profile in Children with Malignant Diseases

Serum levels of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and fructosamine (FA) were determined in thirty–three children with malignant diseases and twenty healthy controls aged 1–14 years. Of them, FA was the parameter measured in children with malignancy for the first time. Mean serum TC, HDL-C, LDL-C and FA showed statistically significant decreases in malignancy compared to healthy children, whereas a statistically significant increase was observed for TG concentrations in serum. From these data, we conclude that significant relations between serum lipids and lipoproteins and the state of malignancy exist in the children studied, and it should be remembered that serum FA concentrations are affected by abnormal serum protein turnover when one deals with any type of neoplastic disease.     

Serum lipoprotein profile in children with celiac disease

Jejunal mucosa is responsible for the absorption of triglycerides and the production of lipoproteins [chylomicrons, very-low-density lipoprotein (VLDL), high-density lipoprotein (HDL)] and apolipoproteins (B-48, A-I, A-II, A-IV, C-II). Mucosal damage is known to cause fat malabsorption and probably also affects the serum lipid profile. To determine lipoprotein production in states of enterocyte dysfunction, we compared the serum lipid profiles in a group of 12 children with untreated celiac disease (flat jejunal mucosa) with the profiles in a control group of 10 children suffering from other intestinal diseases. Statistically significant differences were found in the following parameters (celiac versus control): plasma levels of triglycerides (70 versus 119 mg/dl), cholesterol content in LDL (107 versus 67.7 mg/dl), protein content in VLDL (6 versus 10 mg/dl), and level of apoprotein A-I (112 versus 140 mg/dl). No significant differences were found between the two groups in the serum levels of total cholesterol, the cholesterol content in VLDL and HDL, the protein content in LDL and HDL, and the level of apoprotein B. Following institution of a gluten-free diet, the lipoprotein profile reverted to normal. These data suggest that the changes in the serum lipoprotein profile in celiac disease are secondary to alterations in enterocyte function and not only a reflection of fat malabsorption.     

A comparative study of colestipol and colestyramine in children and adolescents with familial hypercholesterolaemia (author's transl)

Plasma lipids and lipoproteins were studied in 20 children and adolescents with familial hypercholesterolemia during the administration of two anion exchange resins. All the patients' cholesterol levels had been stabilized by treatment with a cholesterol-lowering diet for at least 12 months. Colestyramin (0.6 g per kg body weight) or Colestipol (0.5 g per kg body weight) were given for eight weeks each in a cross-over design. In 6 children, the study had to be terminated due to gastrointestinal problems. Cholesterol, triglycerides and phospholipids were determined serially in whole serum and in isolated lipoprotein fractions. Apolipoprotein-B was determined by radial immunodiffusion in whole serum and in the LDL-fraction. Total plasma cholesterol and LDL cholesterol were lowered by about 25% from initial values of 290 mg/100 ml and 230 mg/100 ml, respectively and Apo-B was lowered by 20%. Low HDL-cholesterol levels in the patients remained decreased during therapy. Triglyceride and phospholipid levels were not affected by treatment. Efficacy, tolerance and side-effects were similar with both Colestyramin and Colestipol.     

Effect of long-term carbamazepine therapy on serum lipids,vitamin B12 and folic acid levels in children

Serum triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), vitamin B12 and folic acid levels were studied in 16 children with epilepsy who had been receiving carbamazepine (CBZ), and in 16 healthy children. Our purpose was to determine whether there was any effect of CBZ therapy on serum lipids, vitamin B12 and folic acid levels. Age ranged from 5 to 19 years (12.25 +/- 3.79 years) and 5.5 to 18 years (12.16 +/- 3.53 years) in the study and control groups, respectively. The duration of CBZ therapy in the patients was between 1 and 4.5 years (3.01 +/- 1.04 years). Serum CBZ level varied between 4 and 12 microg/ml (6.26 +/- 2.07 microg/ml). There was no statistically significant difference in serum triglycerides, TC, HDL-C, LDL-C, VLDL-C or vitamin B12. However, mean folic acid level was found to be lower in the study group than that of the control group (p < 0.05). Nonetheless, serum folic acid levels were within the normal range in all patients. Our study demonstrated that CBZ therapy does not affect serum lipids, vitamin B12 and folic acid levels, and may safely be used with regard to these parameters in children.     

Evaluation of Serum Lipid Levels in Children

This study aimed to establish reference values for serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in children. The study included samples from 4,102 healthy children (2,003 boys and 2,099 girls) ages 1–18 years. The serum levels of total cholesterol, triglycerides, and HDL-C were determined using the Advia 2400 autoanalyzer. The LDL-C levels were calculated using the Friedewald equation. The mean, standard deviation, and 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentile values of the biochemical parameters for boys and girls were detected. The total cholesterol and HDL-C levels were higher among the girls than among the boys in 15- to 18-year-old group. No significant difference was found for the other serum lipid levels among any of the age groups. This study provided pediatric reference intervals for the lipid parameters for children.     

Serum lipid profile in children receiving anti-epileptic drug monotherapy: is it atherogenic?

The effect of anti-epileptic drugs (AEDs) on serum lipid profile is controversial in children as well as in adults. We longitudinally studied serum lipid profile in 34 newly diagnosed epileptic children receiving AED monotherapy with valproic acid (VPA), carbamazepine (CBZ) or phenobarbital (PB). Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), apolipoprotein Al (Apo A1) and apolipoprotein B (Apo B) were measured at baseline and after 2 years of AED monotherapy. Atherosclerotic indices of TC/ HDL-C and Apo A1/Apo B ratios were calculated. Although there were some alterations in serum lipid profile with AED without statistical significance, the atherosclerotic indices of TC/HDL-C and Apo A1/Apo B ratios did not change significantly after 2 years of monotherapy. Only serum TGs levels significantly decreased with VPA monotherapy. These data suggest that 2 years AED monotherapy with VPA, CBZ or PB did not cause a significant level of concern for an atherogenic effect in children with epilepsy.     

Serum homocysteine and lipoprotein (a) concentrations in hypercholesterolemic and normocholesterolemic children

The relationship between lipids, lipoproteins, total homocysteine, and lipoprotein (a) was studied in hypercholesterolemic and normocholesterolemic children. In hypercholesterolemic children, concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein B, and triglycerides were significantly higher compared to levels in controls, whereas concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I were lower compared to those in the control group. Total serum homocysteine concentrations in children with a positive family history for cardiovascular disease CHD(+) (7.28 micromol/L) were significantly higher than those in the control group (5.45 micromol/L), and in the group of CHD(-) children (5.25 micromol/L). The median value of lipoprotein (a) in patients was 31.5 mg/dL (range, 11-209 mg/dL) and in the control group, 19 mg/dL (range, 11-95 mg/dL). Concentrations of Lp (a), exceeding 30 mg/dL, were present in 45% of CHD(+) children, in 29% of CHD(-) children, and in only 11% of the control group.