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  • 1
    ISSN: 1432-1912
    Keywords: Calcium antagonists ; Diltiazem ; Myocardial ischaemia ; Ventricular fibrillation ; Fibrillation threshold
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Calcium antagonists have been reported to decrease the incidence of sudden death in postinfarction management and vulnerability to fibrillation secondary to experimental coronary occlusion. In order to confirm such beneficial results regarding ischaemic ventricular fibrillation, the threshold intensity for fibrillation electrically induced with impulses of 100 ms and 180 beats · min−1 was measured during the course of ischaemias obtained by total occlusion of the left anterior descending coronary artery near its origin in open-chest pigs. The variations of electrical fibrillation threshold with ischaemia duration (30, 60, 120, 180, 240, 360 s) were compared under control conditions and after i.v. diltiazem (0.50 mg · kg−1 plus 0.02 mg · kg−1 · min−1 over 25 min). Electrical fibrillation threshold was not influenced by diltiazem before, but raised during ischaemia, particularly from the 60th s (1.7 to 4.0 mA), with delay in the triggering of fibrillation which occurs when the fibrillation threshold falls down to the pacing threshold (0.2 to 0.3 mA). In 6 pigs out of 8, fibrillation was even avoided in the longest of the ischaemic periods considered (360 s), for fibrillation threshold ceased falling before reaching the critical level. These experimental results obtained with diltiazem are consistent with the clinical effectiveness of calcium antagonists recently observed in the prevention of postinfarction sudden death, provided that myocardial contractility is not too much adversely affected. But, left ventricular dP/dtmax was not reduced by more than 6.8% in the present experiments.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-2665
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Whether the 677C-T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene acts as a risk factor for homocysteine-related vascular disease remains a matter of debate. Testing for the 677C-T nucleotide substitution and assay of plasma homocysteine were carried out simultaneously in 69 controls and 113 vascular disease patients from the Paris area. The variant gene frequency as well as the variant homozygous genotype frequency were very similar in controls and patients. Conversely, plasma homocysteine levels were substantially higher in patients than in controls. A slight interaction between the 677C-T MTHFR polymorphism and homocysteinaemia was observed in the patient group only, while a negative correlation between fasting homocysteine and plasma folate levels was found in all individuals homozygous for the 677C-T MTHFR genotype, irrespective of vascular disease. These data suggest that the 677C-T MTHFR polymorphism is not a major determinant of the vascular disease but contributes to increased plasma homocysteine concentration in conjunction with low plasma folate levels.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of inherited metabolic disease 21 (1998), S. 823-828 
    ISSN: 1573-2665
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe four new mutations in the cystathionine β-synthase gene: three point mutations localized in exons 3, 9 and 10 and one mutation in exon 12 which results in stop codon. Homocystinuria due to cystathionine β-synthase (CBS, EC.4.2.1.22) deficiency (McKusick 236200), is the most common autosomal recessive inborn error of the transsulphuration pathway. Homocystinuric patients exhibit mental retardation, psychotic behaviour, dislocated lenses, vascular disease, osteoporosis and skeletal abnormalities. About 50% of affected subjects show biochemical improvements when treated with pyridoxine, the precursor of the CBS cofactor pyridoxal 5′-phosphate. The severity of the disease varies among the patients: pyridoxine-responsive patients usually have a milder clinical phenotype than pyridoxine-nonresponsive patients. Human CBS cDNA has been cloned and its complete sequence, with minor differences in the coding region, has been published by three teams (Chassé et al 1995; Kraus et al 1993; Kruger and Cox 1994). The screening for mutations in homocystinuric patients has led to the identification of more than 50 mutations (Aral et al 1997; Dawson et al 1996; De Franchis et al 1994; Gallagher et al 1995; Hu et al 1993; Kluijtmans et al 1995; Kozich et al 1993; Kozich and Kraus 1992; Kraus 1994; Marble et al 1994; Shih et al 1995; Sebastio et al 1995; Sperandeo et al 1995). Two mutations are found to be most prevalent: (a) I278T only in pyridoxine-responsive patients; (b) G307S mutation, the leading cause of homocystinuria in Ireland and in patients of ‘Celtic origin’ (Gallagher et al 1995). We describe here four novel mutations at the CBS locus.
    Type of Medium: Electronic Resource
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