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Biomedical subjects

G Leduc

Publications and source records attributed to G Leduc.

At least 19 recordsLinked to original sources

Gene order comparisons for phylogenetic inference: evolution of the mitochondrial genome.

Detailed knowledge of gene maps or even complete nucleotide sequences for small genomes leads to the feasibility of evolutionary inference based on the macrostructure of entire genomes, rather than on the traditional comparison of homologous versions of a single gene in different organisms. The mathematical modeling of evolution at the genomic level, however, and the associated inferential apparatus are qualitatively different from the usual sequence comparison theory developed to study evolution at the level of individual gene sequences. We describe the construction of a database of 16 mitochondrial gene orders from fungi and other eukaryotes by using complete or nearly complete genomic sequences; propose a measure of gene order rearrangement based on the minimal set of chromosomal inversions, transpositions, insertions, and deletions necessary to convert the order in one genome to that of the other; report on algorithm design and the development of the DERANGE software for the calculation of this measure; and present the results of analyzing the mitochondrial data with the aid of this tool.

Biological Evolution

Effects of chlorthalidone and metoprolol alone or in combination (logroton) on blood pressure, lipids, lipoproteins and circulating plasma ANF levels in essential hypertension.

The effects of chlorthalidone (mean dose 25 mg/day), metoprolol (mean dose 200 mg/day) or their combination (logroton) on blood pressure, lipids, lipoproteins and circulating atrial natriuretic factor (ANF) were evaluated in a controlled trial of 42-week duration in 33 hypertensive patients. There was a significant reduction in mean arterial pressure after chlorthalidone and metoprolol treatments. This effect was more pronounced with the chlorthalidone/metoprolol combination (logroton). There were no significant changes in mean ANF levels after any drug regimen, although a tendency to increase was observed after six weeks of treatment with metoprolol. Both chlorthalidone and metoprolol as monotherapy increased the total triglycerides. This effect was less pronounced with logroton. During metoprolol treatment, HDL cholesterol decreased significantly, whereas VLDL-C increased. When combined drug therapy was administered, the unfavorable effects on HDL-C were partially blunted and VLDL-C returned to baseline. LDL-cholesterol did not change significantly during any drug regimen nor did the ratio of LDL-C/HDL-C. Logroton significantly increased the VLDL apo B levels in patients who had received chlorthalidone as monotherapy but had no effect in patients already treated with metoprolol. Neither treatment had a significant influence on the ratio of LDL-C/B. There were no serious adverse events reported throughout the study. It is concluded that logroton may be an effective combination therapy that produces less adverse effects on lipid and lipoprotein metabolism than chlorthalidone or metoprolol monotherapies.

Atrial Natriuretic Factor

Effects of ketanserin on lipids, lipoproteins, and plasma atrial natriuretic factor in patients with essential hypertension.

The effects of ketanserin, 40 mg/day (KE40) and 80 mg/day (KE80) on mean arterial pressure, lipids, lipoproteins, and circulating atrial natriuretic factor (ANF) were investigated in a 24-week controlled study in 29 patients suffering from mild to moderate hypertension. A significant decrease in mean arterial pressure (MAP) was observed after 18 weeks of therapy, accompanied by a 64% (P less than .05) and 80% (P less than .02) increase in circulating ANF levels with KE40 and KE80, respectively. There were no significant changes in mean total cholesterol, triglycerides, or cholesterol of the high density lipoproteins (HDL), low density lipoproteins (LDL), and very low density lipoproteins (VLDL) fractions. There was a significant increase in the mean apo B levels and consequently a slight but statistically significant decrease in the ratio of LDL C/B. It is concluded that both doses of KE are effective for monotherapy of mild to moderate essential hypertension. The drug sharply increases circulating ANF levels without significantly altering the plasma lipids. In contrast, by increasing the apolipoprotein B content of the LDL fraction, the beneficial cardiovascular effect of a lowered blood pressure may be partly blunted.

Atrial Natriuretic Factor

Chronic cyanide poisoning of rainbow trout and its effects on growth, respiration, and liver histopathology.

Cyanide markedly affected growth and resting metabolic rate while causing degenerative hepatic necrosis in juvenile rainbow trout (Salmo gairdneri, Richardson). This was revealed during two experiments performed in continuously renewed water at 12.5 degree C with fish fed a restricted artificial diet and exposed to assayed cyanide concentrations of 0.00, 0.01, 0.02, or 0.03 mg/L hydrogen cyanide (HCN) for 18 days. At 0.02 and 0.03 mg/L, HCN growth was reduced by 40 to 95% after 18 days. At all concentrations, cyanide caused a severe initial repression of specific growth rate, followed by a highly significant increase which was insufficient to compensate for the original repression. Previous exposure to cyanide promoted a higher resting metabolic rate during the six days following exposure, the effect increasing with cyanide concentration. At all concentrations tested, widespread cyanide-induced degenerative necrosis of hepatocytes was observed; it was more intense at higher cyanide concentrations and well established even at 0.01 mg/L HCN.

Animals

Effects of metoprolol and propranolol on lipid metabolism.

Treatment of five hypertriglyceridemic and one normolipemic patients with propranolol, a non-selective beta-blocking agent, and metoprolol, which is generally considered to be a cardioselective beta-adrenoceptor antagonist, was observed to produce a further elevation in their triglyceride levels. The subjects were followed for 20 weeks, during which they received propranolol for eight weeks, a placebo for four weeks and metoprolol for eight weeks in a crossover design. The analysis suggested that the increase in triglyceride levels was less pronounced with the more cardioselective agent. Moreover, alpha-cholesterol decreased significantly after propranolol but remained constant while on metoprolol. Both drugs decreased beta-cholesterol whereas chylo- and pre- beta-cholesterol increased, particularly with propranolol. Considering the contradictory evidence regarding the clinical importance of chronic elevation of plasma triglyceride and decreased alpha- und beta-cholesterol concentrations, it is suggested that a cardioselective drug would be presently preferable in hyperlipidemic subjects.

Cholesterol

[Study of interventricular septal defects with equal aortic and pulmonary artery pressures. Classification by clinical and computer methods of 70 cases].

Application of various methods of classification to a group of 70 cases of ventricular septal defect with high pulmonary artery hypertension allowed a comparative study between the various methods aiming at distinguishing the forms with low from high pulmonary artery resistance. The reference clinical classification provides supplementary informations derived from the natural or post-operative course and eventually from the microscopic examination. The first automatic classification relies on the study of a single criterion: the pulmonary arteriolar resistance and the systemic resistance ratio. A second classification is based on the attribution of points to some clinical or haemodynamic signs resulting in a score orienting the classification of every individual. Multifactorial analysis methods deal with all the available informations for the overall group, and suppose the use of a computer. The informatic methods make it possible to study the classifying value of every sign. Correlations were established between these various techniques and the medical classification.

Adolescent

Screening programs for hypertension.

MAJOR SCREENING PROGRAMS FOR HYPERTENSION ARE NECESSARY FOR THE FOLLOWING REASONS: (a) the 12 to 15% prevalence of hypertension in the North American population; (b) the high proportion of hypertensive patients who are inadequately treated or whose disease is not even recognized; (c) the fact that in too many medical centres hypertension is poorly investigated or considered an insignificant finding; (d) the demonstration by many groups, especially the Framingham study, of hypertension as the major factor in the occurrence of severe cardiovascular disease; and (e) the achievement of a marked decrease in severe cardiovascular complications following adequate treatment. But such screening programs are of little value if unaccompanied by a major educational effort directed not only to the public but also to the medical profession, and a parallel increase in the funding of biomedical research into the basic physiopathological mechanisms of hypertension.

Adolescent