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S Lepage

Publications and source records attributed to S Lepage.

36 records · Page 2Linked to original sources
PubMed1995

Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.

OBJECTIVES: This study compared the effects of amlodipine, atenolol and their combination on ischemia during treadmill testing and 48-h ambulatory monitoring. BACKGROUND: It is not known whether anti-ischemic drugs exert similar effects on ischemia during ambulatory monitoring and exercise treadmill testing. METHODS: Patients with stable coronary artery disease and ischemia during treadmill testing and ambulatory monitoring were randomized to receive amlodipine (n = 51) or atenolol (n = 49). Each group underwent a counterbalanced, crossover evaluation of single drug and placebo, followed by evaluation of the combination. RESULTS: Amlodipine and the combination prolonged exercise time to 0.1-mV ST segment depression by 29% and 34%, respectively (p < 0.001) versus 3% for atenolol (p = NS). During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p = 0.083 [NS]), by 57% with atenolol (p < 0.001) and by 72% with the combination (p < 0.05 vs. both single drugs; p < 0.001 vs. placebo). Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina. Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.005 vs. placebo, atenolol and amlodipine). In patients with angina, total exercise time improved by 16% with amlodipine (p < 0.001), by 4% with atenolol (p = NS) and by 19% with the combination (p < 0.05 vs. placebo and either single drug). In those patients without angina, no therapy significantly improved total exercise time. CONCLUSIONS: Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination was more effective than either single drug in both settings.

Amlodipine↗
PubMed1995

Saturation of penicillin-binding protein 1 by beta-lactam antibiotics in growing cells of Bacillus licheniformis.

With the help of a new highly sensitive method allowing the quantification of free penicillin-binding proteins (PBPs) and of an integrated mathematical model, the progressive saturation of PBP1 by various beta-lactam antibiotics in growing cells of Bacillus licheniformis was studied. Although the results confirmed PBP1 as a major lethal target for these compounds, they also underlined several weaknesses in our present understanding of this phenomenon. In growing cells, but not in resting cells, the penicillin target(s) appeared to be somewhat protected from the action of the inactivators. In vitro experiments indicated that amino acids, peptides and depsipeptides mimicking the peptide moiety of the nascent peptidoglycan significantly interfered with the acylation of PBP1 by the antibiotics. In addition, the level of PBP1 saturation at antibiotic concentrations corresponding to the minimum inhibitory concentrations was not constant, suggesting that additional, presently undiscovered, factors might be necessary to account for the experimental observations.

Acylation↗
PubMed1994

Synthesis, purification and kinetic properties of fluorescein-labelled penicillins.

The synthesis and properties of six fluorescein-labelled penicillins are reported. The two isomers of fluoresceyl-glycyl-6-amino-penicillanic acid are probably the best compounds to use for detection of all the penicillin-binding proteins (PBPs) present in a bacterial membrane preparation. However, the derivatives of ampicillin were much more efficient against Enterobacter aerogenes PBP3. The two isomers obtained when a commercial mixture of the two isomers of carboxyfluorescein was used most often exhibited similar properties, but the Streptomyces R61 extracellular DD-peptidase was only efficiently acylated by the 5'-carboxyfluorescein derivative of glycyl-6-aminopenicillanic acid.

Bacterial Proteins↗
PubMed1994

[Stability of alpha-tocopherol: pre-analytical conditions in its determination in blood samples].

Incomplete and controversial data exist concerning vitamin E or alpha-tocopherol stability in biological samples. Recent clinical interest in the protective function of alpha-tocopherol provided another reason for the setting-up of a multicenter study by the Sociéte Française de Biologie Clinique. Our purpose was to examine the effects on alpha-tocopherol stability, firstly, of collection and transportation of blood samples, and, secondly, of the temperature (-20 degrees C and -80 degrees C) and period of storage of serum or plasma. alpha-tocopherol was determined in serum or plasma by isocratic liquid chromatography with UV detection at 292 nm. Our results established that alpha-tocopherol was extremely stable in blood, serum or plasma over 8 hours without special handling conditions (light, temperature). Pools of serum or plasma were stable for at least 3 months at -20 degrees C and -80 degrees C. They are suitable for use in the quality control of alpha-tocopherol. On the other hand, in some samples, we observed great variability in the rate of alpha-tocopherol degradation. However, there was lesser degradation when these plasma samples were stored at -80 degrees C instead of -20 degrees C. We therefore do not advise storing serum or plasma for more than 1 month at -20 degrees C for more than 3 months at -80 degrees C. This latter temperature is recommended in epidemiological studies.

Adult↗
PubMed1993

Relative importance of psychologic traits and severity of ischemia in causing angina during treadmill exercise. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.

OBJECTIVES: This study was conducted to compare the influence of psychologic traits versus ischemia severity on the occurrence of angina during treadmill exercise. BACKGROUND: Some studies suggest that angina is associated with certain psychologic traits, whereas others show an association with more severe ischemia. The relative influence of these two factors and the extent to which they interact are not known. METHODS: Off-drug treadmill exercise testing and a battery of psychologic tests were performed on 122 patients with known coronary artery disease. Psychologic tests measured sensitivity to physical symptoms, denial and deception, type A behavior, anger, hostility, depression, marital adjustment and amount of external stress. Stepwise logistic regression was used to determine the independent association of psychologic traits, ischemic threshold and exercise tolerance with the occurrence of angina. RESULTS: Angina during treadmill exercise was reported by 66 of 122 patients. On univariate testing, angina was positively associated with sensitivity to physical symptoms (p < 0.001), type A behavior (p = 0.021) and depression (p = 0.032) and was negatively associated with exercise tolerance (p < 0.001) and work load threshold for ischemia (p < 0.01). Multivariate analysis revealed independent and additive associations of angina with sensitivity to physical symptoms (p = 0.003), exercise capacity (p = 0.003) and work load threshold for ischemia (p = 0.018). Once these were included in a logistic model, depression and type A behavior were no longer significant. Other psychologic traits showed no association with angina. CONCLUSIONS: Sensitivity to physical symptoms, ischemic threshold and exercise tolerance are independently associated with angina, with sensitivity to physical symptoms having the stronger influence. The physiologic and psychologic mechanisms underlying symptom perception have an influence on angina that is independent of and additive to the severity of underlying ischemia.

Amlodipine↗
PubMed1993

Massive hydrothorax complicating peritoneal dialysis. Isotopic investigation (peritoneopleural scintigraphy).

Massive hydrothorax occurring during continuous ambulatory peritoneal dialysis is a rare complication that may appear at any time during the course of the treatment. Most of the time, it is right-sided and is more frequent in female patients. A case is presented that was investigated by peritoneopleural scintigraphy. A rapid accumulation of the radiopharmaceutical over the right hemithorax was observed. To explain that finding, a macroscopic diaphragmatic defect was suspected. Different therapeutic approaches are presented.

Female↗
PubMed1993

Cardiovascular changes during an isometric contraction combined to a cold pressor test.

Fifteen normotensive male subjects (age, 27.9 +/- 1.3 years) performed isometric contractions (handgrip) at 15, 30 and 50% maximal voluntary contraction respectively for 7, 3 and 1 min. The contractions were sustained with or without a cold pressor test of the same duration (immersion of one foot in water of 5.2 +/- 0.1 degrees C). At rest, under the influence of a cold pressor test for 3 min, the heart rate increased from 74.3 +/- 2.2 to 83.3 +/- 2.1 beats min-1 (P < 0.001) in less than 10 s, and returned to the control value in 3 min; on the contrary, at the end of 3 min of cold pressor test, the systolic blood pressure was still above the control value (135.5 +/- 4.2 and 121.0 +/- 3.2 mmHg, P < 0.001). During the contractions, there was no significant difference between heart rate and systolic blood pressure values obtained with or without cold pressor test. Similarly, there was no significant change in the concentrations of plasma catecholamines. This absence of cardiovascular effect of cold pressor test associated with isometric contraction (for three relative force levels) is probably due to the increasing importance of sympathetic cardiac activation produced by the contraction with respect to that produced by the cold pressor test, the absence of supplementary changes in total peripheral resistance and a partial reciprocal inhibition of pain produced by the simultaneous performance of these two tests.

Adult↗
PubMed1993

[Peroxidation of human high density lipoproteins by oxygen-derived free radicals].

The involvement of low density lipoprotein (LDL) peroxidation in atherogenesis is now admitted. The oxidation of high density lipoproteins (HDL) could contribute to the atherogenic process, by limiting their capacity to accept cholesterol from cell membranes. In this work, we studied the human HDL peroxidation initiated by OH. or OH./O2.- free radicals generated by gamma radiolysis. This method allows a quantitative and selective production of free radicals, and the resulting oxidation is less drastic than the chemical one. HDL oxidation was followed, as a function of the radiation dose, by the disappearance of endogenous vitamin E, the formation of thiobarbituric acid-reactive substances (TBARS) and the fluorescence at 440 nm. Human HDL turned out to be oxidizable by hydroxyl free radicals and oxygen potentiated this effect. The oxidative modification of HDL, leading to a rigidification of the HDL envelop, could contribute to reduce the ability of HDL to stimulate efflux of cholesterol from tissues.

Free Radicals↗
PubMed1992

Primary and predicted secondary structures of the Actinomadura R39 extracellular DD-peptidase, a penicillin-binding protein (PBP) related to the Escherichia coli PBP4.

As derived from gene cloning and sequencing, the 489-amino-acid DD-peptidase/penicillin-binding protein (PBP) produced by Actinomadura R39 has a primary structure very similar to that of the Escherichia coli PBP4 [Mottl, Terpstra & Keck (1991) FEMS Microbiol. Lett. 78, 213-220]. Hydrophobic-cluster analysis of the two proteins shows that, providing that a large 174-amino-acid stretch is excluded from the analysis, the bulk of the two polypeptide chains possesses homologues of the active-site motifs and secondary structures found in the class A beta-lactamase of Streptomyces albus G of known three-dimensional structure. The 174-amino-acid insert occurs at equivalent places in the two PBPs, between helices alpha 2 and alpha 3, away from the active site. Such an insert is unique among the penicilloyl serine transferases. It is proposed that the Actinomadura R39 PBP and E. coli PBP4 form a special class, class C, of low-Mr PBPs/DD-peptidases. A vector has been constructed and introduced by electrotransformation in the original Actinomadura R39 strain, allowing high-level expression and secretion of the DD-peptidase/PBP (250 mg.l-1). The gene encoding the desired protein is processed differently in Actinomadura R39 and Streptomyces lividans. Incorrect processing in Streptomyces lividans leads to a secreted protein which is inert in terms of DD-peptidase activity and penicillin-binding capacity.

Actinomycetales↗
PubMed1992

Effect of pH on low-density lipoprotein oxidation by O2-./HO2. free radicals produced by gamma radiolysis.

This study aimed to analyze quantitatively the initiation and the consequences of low-density lipoprotein (LDL) peroxidation by O2-./HO2. free radicals produced by gamma radiolysis. The action of increasing radiation doses on aqueous LDL solutions has been monitored simultaneously by several parameters: a decrease in endogenous vitamin E, the formation of thiobarbituric acid-reactive substances (TBARS) and conjugated dienes, the appearance of a differential fluorescence (excitation wavelength = 360 nm), and an increase of the relative electrophoretic mobility. Initial radiation yields (decrease in vitamin E, formation of TBARS) have been determined at pH 7 and pH 5.7 as a function of LDL concentration (from 0.75 to 9 g liter-1). From the comparison of these yields with those of O2-. radicals produced by water radiolysis, we have deduced reaction mechanisms for LDL peroxidation initiated by O2-./HO2. free radicals.

Dose-Response Relationship, Drug↗
PubMed1992

Simple method for quantifying alpha-tocopherol in low-density+very-low-density lipoproteins and in high-density lipoproteins.

We assessed the distribution of alpha-tocopherol in serum lipoprotein samples after separating the lipoprotein fractions by either sequential ultracentrifugation or selective precipitation with sodium phosphotungstate-magnesium chloride reagent. alpha-Tocopherol concentrations were determined by reversed-phase high-performance liquid chromatography. After ultracentrifugation, we found that in men, low- and very-low-density serum lipoproteins (LDL-VLDL) contained 53.6% of alpha-tocopherol vs 46.4% in high-density lipoproteins (HDL). In women, serum LDL-VLDL contained 45.6% alpha-tocopherol after ultracentrifugation vs 54.4% in HDL. After selective precipitation, the proportions of alpha-tocopherol in men were 56.1% in LDL-VLDL vs 43.9% in HDL, and in women, 45.4% in LDL-VLDL vs 54.6% in HDL. After selective precipitation, alpha-tocopherol recovery from whole lipoprotein fractions was 97% to 100% vs 80% after ultracentrifugation, thus allowing more accurate alpha-tocopherol quantification than after separation by ultracentrifugation.

Adult↗
PubMed1990

Role of the conserved amino acids of the 'SDN' loop (Ser130, Asp131 and Asn132) in a class A beta-lactamase studied by site-directed mutagenesis.

Ser130, Asp131 and Asn132 ('SDN') are highly conserved residues in class A beta-lactamases forming one wall of the active-site cavity. All three residues of the SDN loop in Streptomyces albus G beta-lactamase were modified by site-directed mutagenesis. The mutant proteins were expressed in Streptomyces lividans, purified from culture supernatants and their kinetic parameters were determined for several substrates. Ser130 was substituted by Asn, Ala and Gly. The first modification yielded an almost totally inactive protein, whereas the smaller-side-chain mutants (A and G) retained some activity, but were less stable than the wild-type enzyme. Ser130 might thus be involved in maintaining the structure of the active-site cavity. Mutations of Asp131 into Glu and Gly proved to be highly detrimental to enzyme stability, reflecting significant structural perturbations. Mutation of Asn132 into Ala resulted in a dramatically decreased enzymic activity (more than 100-fold) especially toward cephalosporin substrates, kcat. being the most affected parameter, which would indicate a role of Asn132 in transition-state stabilization rather than in ground-state binding. Comparison of the N132A and the previously described N132S mutant enzymes underline the importance of an H-bond-forming residue at position 132 for the catalytic process.

Amino Acid Sequence↗
PubMed1986

Ascites and right pleural effusion: demonstration of a peritoneo-pleural communication.

A 54-yr-old female with known liver cirrhosis presented with a right transudative pleural effusion and ascites. To find the source of pleural fluid, [99mTc]sulfur colloid was injected intraperitoneally and a serial imaging study revealed its passage to the right pleural space on 2-hr and 24-hr images. Mechanisms proposed in the formation of pleural effusion in liver cirrhosis are (a) lymphatic drainage and (b) diaphragmatic defect. Radioisotope migration speed may be a clue for differentiating these two mechanisms, being more rapid in the presence of a diaphragmatic defect.

Ascites↗
PubMedDate not supplied

Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography: from the Investigators of Consensus on Diastolic Dysfunction by Echocardiography.

Abnormalities of diastolic filling are increasingly recognized as a cause of symptoms and predictors of outcome in patients with most forms of heart disease. Noninvasive assessment of diastolic filling is possible in almost all patients, but accurate evaluation must relate echocardiographic Doppler measurements to the complex physiologic and hemodynamic factors responsible for normal and abnormal filling. This evaluation has been facilitated by recent correlation of Doppler measurement of mitral and pulmonary venous inflow with hemodynamic studies. These studies have confirmed that when a careful, integrated approach is taken, Doppler flow patterns can document a progressive pattern of abnormality in many conditions. Impaired left ventricular (LV) relaxation is seen early and is recognized by a decrease in early transmitral LV filling and an increased proportion of filling during atrial contraction. As abnormalities progress, increasing LV chamber stiffness and elevated left atrial pressure lead to a "pseudonormal" filling pattern that previously has caused considerable confusion. This can be unmasked by careful evaluation of pulmonary venous inflow and the use of the Valsalva maneuver. When marked diastolic abnormalities are present, LV filling has restrictive features characterized by rapid early filling, a very stiff left ventricle with high filling pressures, and a poor prognosis. Routine measurement of indexes of diastolic filling have been hampered by uncertainty as to what should be measured, what techniques should be used, definition of normal values, and a clear method of reporting findings. This report represents the efforts of a Canadian consensus group to define a national standard for the performance and reporting of echocardiographic Doppler studies of diastolic filling.

Aged↗