Biomedical subjects

M Lelièvre

Publications and source records attributed to M Lelièvre.

9 recordsLinked to original sources

PubMed1998

Association of specific LDL receptor gene mutations with differential plasma lipoprotein response to simvastatin in young French Canadians with heterozygous familial hypercholesterolemia.

In familial hypercholesterolemia (FH), the efficacy of the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase shows considerable interindividual variation, and several genetic and environmental factors can contribute to explaining this variability. A randomized, double-blind, placebo-controlled clinical trial with simvastatin, an HMG-CoA reductase inhibitor, was conducted in 63 children and adolescents with heterozygous FH. The patients were grouped according to known LDL receptor genotype. After 6 weeks of treatment with 20 mg/d simvastatin, the mean reduction in plasma LDL cholesterol in patients with the W66G mutation (n=14) was 31%, whereas in the deletion>15 kb (n=23) and the C646Y mutation groups (n=10), it was 38% and 42%, respectively (P<0.05). After treatment with simvastatin, HDL cholesterol levels were increased in all groups, and triglyceride concentrations were significantly reduced. Multiple regression analyses suggested that 42% of the variation of the LDL cholesterol response to simvastatin can be attributed to variation in the mutant LDL receptor locus, apolipoprotein E genotype, and body mass index, while 35% of the variation in HDL cholesterol response was explained by sex and baseline HDL cholesterol. These results show that simvastatin was an effective and well-tolerated therapy for FH in the pediatric population for all LDL receptor gene mutations. Moreover, the nature of LDL receptor gene mutations and other genetic and constitutional factors play a significant role in predicting the efficacy of simvastatin in the treatment of FH in children and adolescents.

Adolescent↗

PubMed1993

Hypothalamic dysfunction in a child: a distinct syndrome? Report of a case and review of the literature.

We report the case of a 9-year-old girl with multiple problems due to hypothalamic dysfunction of obscure origin: apnoeic spells, behavioural problems, developmental delay, hypodipsia with bouts of hypernatraemia, episodes of spontaneous hypothermia, obesity, petit-mal seizures, non-progressive precocious puberty, absence of respiratory response to CO2 and probably insensitivity of hyposensitivity to pain. She also had hyperprolactinaemia and decreased human growth hormone secretion. Hypothyroidism of central origin and hyposecretion of cortisol were also present. Multiple brain CT-scans failed to reveal any tumour or other anatomical abnormality. Her clinical course was improved initially by treatment with clomipramine, but she died suddenly, and the autopsy failed to disclose any anatomical lesion. We compare this case with three similar previously reported cases.

Child↗

PubMed1981

Ammonia metabolism in a family affected by hyperargininemia.

A French-Canadian family, with a 14-year old mentally retarded girl, was investigated for hyperargininemia. The girl showed a fasting plasma ammonia N concentration of 100 micrograms/dl (normal : 50.5 +/- 13 micrograms/dl), and a two-hour post protein load level of 183 micrograms/dl (normal : 51.6 +/- 17.6 micrograms/dl). Plasma urea N was lower than normal in the post-load sample. Arginine concentrations were 11 times normal in the plasma, 47 times normal in the urine and 4 times normal in erythrocytes. Measurement of erythrocyte arginase showed only 1% activity in the propositus, and 52-54% in the parents and a sibling as compared to controls. In heterozygous members of the family, the Km (arginine) was similar to controls. Column chromatography of serum amino acids in the propositus showed arginine to be 17.6 S.D. higher than the normal mean. A characteristic cystine-lysinuria pattern of urinary amino acids was also seen. Measurement of other urinary nitrogenous metabolites showed low urinary urea and excessive orotic aciduria. On "normal" food intake, the patient excreted 122 mg of orotic acid/24 h, as against 3.7 mg by the sibling and 3.9 mg by the mother. It is postulated that the level of ornithine in hepatocyte mitochondria is critical to the disposal of carbamyl phosphate. The lack of normal regeneration of ornithine by liver arginase, and an excessive urinary excretion may be responsible for its low mitochondrial concentration. This would cause diversion of unmetabolised carbamyl phosphate towards orotic acid synthesis or ammonia production.

Adolescent↗

PubMed1977

Plasma lipids and lipoprotein patterns in angiographically graded atherosclerosis of the legs and in coronary heart disease.

The prevalence and type of plasma lipoprotein abnormalities were determined in 114 French-Canadian patients with angiographically proven peripheral vascular disease (PVD). The severity of atherosclerosis was positively correlated with plasma triglyceride concentration, especially in the younger patients (r = 0.29, P less than 0.05), and (not significantly) with plasma cholesterol concentration. Of the risk factors believed to predispose individuals to atherosclerosis, cigarette smoking was the most frequently found in the PVD patients (72.8%), especially among the men. Combination of two or more risk factors was the rule. Findings were compared with those in 114 patients who had undergone coronary angiography for suspected coronary heart disease (CHD). The CHD patients were, on average, younger by 10 years. Hyperlipidemia was present in 58.8% of CHD patients, compared with 43.9% of PVD patients. A far higher proportion of CHD patients showed the type II plasma lipoprotein pattern (24.6% v. 7.9%), although the type IV pattern was more common in both groups (31.6% and 28.9%, respectively). A high proportion of all patients (56.1% with PVD and 41.2% with CHD) showed a normal lipoprotein pattern on paper electrophoresis.

Adult↗

PubMed1975