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Biomedical subjects

M Lessard

Publications and source records attributed to M Lessard.

At least 55 records · Page 3Linked to original sources
PubMed1995

Simultaneous determination of diltiazem and quinidine in human plasma by liquid chromatography.

A novel method for simultaneous determination of diltiazem and quinidine in human plasma is described. Plasma is alkalinized and extracted with methyl tert.-butyl ether. The ether phase is separated and evaporated. The residue is reconstituted in 0.2 ml of mobile phase containing 56 mM octanesulfonic acid then washed twice with n-hexane. Aliquots are chromatographed on a silanol-deactivated reversed-phase column using a mobile phase containing aqueous H2SO4 (0.01 M, pH 2)-methanol-acetonitrile (45:45:10) and 10 mM octanesulfonic acid. Peaks are monitored with a UV detector set at 237 nm and a fluorescence detector using an excitation set at 247 nm and a 270 nm UV cut-off filter at the emission. Calibration and standard curves were linear from 1 to 130 ng on-column for diltiazem and from 2 to 600 ng on-column for quinidine. Limits of quantitation were 2 and 4 ng/ml for diltiazem and quinidine, respectively. Recoveries from spiked plasma were 94.0 to 102.5% (R.S.D. 6.0-11.4%) for diltiazem and 98.5% to 104.1 (R.S.D. 7.7-8.7%) for quinidine over the ranges studied. In vitro stability was studied in spiked plasma samples stored at -80 degrees C for sixteen months. Both diltiazem and quinidine remained within 10% from nominal values. For ex vivo stability at -80 degrees C, a plasma sample obtained from a volunteer 2 h after oral administration of diltiazem (60 mg) was analysed for two days after sampling and eighteen months later. The mean deviation from initial measured was 4.7%.

Chromatography, High Pressure Liquid↗
PubMed1995

Inorganic cation dependence of putrescine and spermidine transport in human breast cancer cells.

The mechanism of polyamine uptake in mammalian cells is still poorly understood. The role of inorganic cations in polyamine transport was investigated in ZR-75-1 human breast cancer cells. Although strongly temperature dependent, neither putrescine nor spermidine uptake was mediated by a Na+ cotransport mechanism. In fact, Na+ and cholinium competitively inhibited putrescine uptake relative to that measured in a sucrose-based medium. On the other hand, ouabain, H+, Na+, and Ca2+ ionophores, as well as dissipation of the K+ diffusion potential, strongly inhibited polyamine uptake in keeping with a major role of membrane potential in that process. Polyamine transport was inversely dependent on ambient osmolality at near physiological values. Putrescine transport was inhibited by 70% by decreasing extracellular pH from 7.2 to 6.2, whereas spermidine uptake had a more acidic optimum. Deletion of extracellular Ca2+ inhibited putrescine uptake more strongly than chelation of intracellular Ca2+. In fact, bound divalent cations were absolutely required for polyamine transport, as shown after brief chelation of the cell monolayers with EDTA. Either Mn2+, Ca2+, or Mg2+ sustained putrescine uptake activity with high potency (Km = 50-300 microM). Mn2+ was a much stronger activator of spermidine than putrescine uptake, suggesting a specific role for this metal in polyamine transport. Other transition metals (Co2+, Ni2+, Cu2+, and Zn2+) were mixed activators/antagonists of carrier activity, while Sr2+ and Ba2+ were very weak agonists, while not interfering with Ca2+/Mg(2+)-dependent transport. Thus, polyamine uptake in human breast tumor cells is negatively affected by ionic strength and osmolality, and is driven, at least in part, by the membrane potential, but not by the Na+ electrochemical gradient. Moreover, the polyamine carrier, or a tightly coupled accessory component, appears to have a high-affinity binding site for divalent cations, which is essential for the uptake mechanism.

Biological Transport↗
PubMed1995

Hormonal and feedback regulation of putrescine and spermidine transport in human breast cancer cells.

The properties and regulation of the mammalian polyamine transport system are still poorly understood. In estrogen-responsive ZR-75-1 human breast cancer cells, which display low polyamine biosynthetic activity, putrescine and spermidine were internalized with high affinity (Km = 3.7 and 0.5 microM, respectively) via a single class of saturable transporter shared by both substrate types, or via distinct but closely similar carriers. The Vmax, but not the Km of polyamine transport was rapidly and synergistically up-regulated by estrogens and insulin. The steady decay in transport activity observed in hormone-deprived cells was accelerated by retinoic acid. The enhancement of uptake activity resulting from polyamine depletion was amplified 3-fold by estrogens and insulin despite profound growth inhibition, indicating that the cooperative hormonal induction of polyamine transport is dissociated from cell growth status. Polyamine uptake was under feedback inhibition by at least three distinct mechanisms in these cells, namely (i) the induction of a short-lived protein not actively synthesized without ongoing uptake or upon polyamine deletion; (ii) a more latent, protein synthesis-independent "trans-inhibition" mechanism; and (iii) a post-carrier, cycloheximide-sensitive mechanism limiting substrate accumulation. The complexity of these multiple levels of feedback transport inhibition is in keeping with the cytotoxicity of excessive polyamine content.

Biological Transport↗
PubMed1994

Flow velocity profile of the fetal aortic isthmus through normal gestation.

Experimental and clinical evidence have demonstrated that an increase in resistance to placental blood flow causes changes in aortic isthmic diastolic flow profile before any significant modification is observed in umbilical artery Doppler waveforms. To identify these abnormal flow profiles, the objective of this study was to document the normal flow profile in the aortic isthmus throughout pregnancy. The study included 81 normal fetuses from 17 to 39 weeks of gestation. On the isthmic flow profile, an index, named the balance index, was calculated: (peak systolic--end-diastolic velocities/forward--reverse flow velocity integrals). Before 20 weeks of gestation, a forward flow was recorded throughout the cardiac cycle and the diastolic deceleration phase was gradual and smooth. After 20 weeks, an incisura appeared at end-systole that progressively increased, and by 30 weeks of gestation a brief reverse diastolic flow was constantly recorded. The balance index increased slightly throughout gestation. Color flow mapping demonstrated that the reverse flow observed late in gestation in the isthmus was coming from the ductus arteriosus. In conclusion, the morphology of the Doppler flow velocity waveform of the fetal aortic isthmus changes with gestation. The proposed balance index may be useful in identifying fetuses with disturbed peripheral hemodynamics.

Analysis of Variance↗
PubMed1994

Influence of low-level exposure to Fusarium mycotoxins on selected immunological and hematological parameters in young swine.

The effects of low dietary concentrations of Fusarium mycotoxins (deoxynivalenol (DON), 15-acetyl-DON, and zearalenone) on growth, immunological, and hematological parameters were determined in young pigs during a 28-day feeding experiment. Clean and naturally contaminated corn were incorporated into basal diets formulated to contain 0.00, 0.75, 1.50, and 3.00 mg DON/kg diet. A pair-fed control animal was used for comparison with each animal receiving the highest level of contamination (diet 4). Skin temperature, measured during the first week of the experiment, decreased linearly as the dietary mycotoxin concentration increased. Several other linear effects were observed: depressed feed intake throughout the experiment, reduction in thyroid size (absolute/relative), and changes in the appearance of the esophageal region of the stomach (thicker and higher degree of folding with increasing toxin concentration). Serum T4 (thyroxine) levels increased quadratically after 7 and 28 days of exposure compared to control animals. This change coincided with an increase in albumin levels, a decrease in alpha-globulin levels, and an overall increase in albumin/globulin ratio as the level of contamination increased. After immunization with sheep red blood cells (SRBC), animals fed contaminated diets showed a delayed response in peak titers. At the end of the experiment an increase in the segmented neutrophil count was observed. The following observations were made for animals consuming diet 4 as compared to the pair-fed controls: lower skin temperature, better feed efficiency, more corrugated stomachs, reduced alpha-globulin levels, and lower antibody titers to SRBC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1994

Trisomy 8q due to i(8q) or der(8) t(8;8) is a frequent lesion in T-prolymphocytic leukaemia: four new cases and a review of the literature.

Cytogenetic abnormalities found in four cases of T-cell prolymphocytic leukaemia (T-PLL) are described. An isochromosome 8q was found in three patients and a t(8;8) in one. In the four cases, karyotypes were complex and showed a high degree of instability. In addition, we reviewed 27 published cases of cytogenetically studied T-PLL. On the whole, the most frequently recurring anomalies in T-PLL are 14q lesions with nonrandom breakpoints, inversion (14)(q11q32) or tandem translocations (14;14) (not seen in any of our cases) and trisomy for 8q. mainly due to i(8q), found in more than 40% of patients each. Similar structural anomalies were found almost as frequently among the 23 cytogenetically studied cases of so-called T-chronic lymphocytic leukaemia (T-CLL) reported prior to 1989. It is now accepted that the T-cell counterpart of B-CLL either does not exist or is exceedingly rare and thus previously reported cases of T-CLL sharing the chromosomal characteristics of T-PLL may well have been misdiagnosed examples of T-PLL. Isochromosomes 8q are exceptionally found in other types of haematological malignancies. However, i(8q) could not be shown to be the primary lesion in any case in T-PLL and the role of trisomy for 8q, as well of the associated monosomy 8p, is entirely unknown.

Adult↗
PubMed1993

Reference values for Doppler velocimetric indices from the fetal and placental ends of the umbilical artery during normal pregnancy.

A range-gated Doppler ultrasound system combined with a real-time imaging system was used to determine arterial blood velocity values from the fetal and placental ends of the umbilical cord in 269 normal pregnancies between 17 and 40 weeks, menstrual age. The systolic-diastolic ratio (S/D), pulsatility index (PI), and resistance index (RI) were higher at the fetal end compared to the placental end of the cord. The individual differences in these Doppler indices, obtained between the fetal and placental recording sites, were inversely related to menstrual age: S/D: r = -0.38, p < 0.001; PI: r = -0.25, p < 0.001; and RI: r = -0.15, p < 0.01. After normalization for the angle of insonation, the peak systolic velocity was higher and the end-diastolic velocity was lower at the fetal than at the placental end of the cord. It is concluded that routine recordings for Doppler velocimetric indices should take into account the recording site on the umbilical cord in order to reduce methodological sources of variance, especially during midgestation. Furthermore, the data presented here in the form of the median and percentile values are proposed as normal reference values to facilitate this procedure.

Blood Flow Velocity↗
PubMed1993

Fetal central blood flow alterations in human fetuses with umbilical artery reverse diastolic flow.

Blood flow velocimetry studies in animal fetuses with reverse diastolic flow in the umbilical artery have shown marked changes in the fetal central circulation characterized by a retrograde diastolic flow in the descending aorta, and as far as the aortic arch, along with a significant forward diastolic flow in the arteries going to the brain. Documentation and the implications of this phenomenon in human fetuses, to date, have not been reported. Doppler echographic evaluations of the diastolic patterns in the umbilical artery, descending aorta, the aortic arch, and the common carotid artery were performed on 5 fetuses in whom reverse diastolic flow was observed in the umbilical artery. In all five cases reverse diastolic flow was observed not only in the umbilical artery but also in the aortic arch. In the carotid artery, however, a forward diastolic flow was always recorded. It can be concluded, by inference, that in these fetuses, the area of lowest resistance was no longer the placenta, as seen in normal conditions, but the cerebral circulation. Furthermore, in four fetuses the retrograde component of the flow profiles was more prominent in the aortic arch compared with the descending aorta, suggesting that, in diastole, blood was coming from the pulmonary artery through the ductus arteriosus.

Adult↗
PubMed1993

Translocation t(1;19) in acute lymphoblastic leukemia patients with cytological presentation simulating L3-ALL (Burkitt-like).

The t(1;19) in B-lineage ALL is classically associated with a FAB L1/L2 phenotype and the expression of cIg. Recent reports have demonstrated immuno-phenotypic and molecular heterogeneity among cases demonstrating apparently identical karyotypic abnormalities. We report 5 cases of t(1;19) with cytological features resembling an L3 (Burkitt-like) phenotype, suggesting that accurate assessment of these cases requires detailed correlation of cytological, immunological and molecular characteristics.

Adult↗
PubMed1993

Suppressive effect of serum from pigs and dogs fed a diet deficient in vitamin E and selenium on lymphocyte proliferation.

The effect of sera collected from either pigs or dogs previously fed a vitamin E (vit E)- and selenium (Se)-deficient diet on in vitro lymphocyte blastogenesis response to mitogens was studied. Porcine sera were obtained from pigs used in 2 different trials. In I trial, 4-wk-old pigs received either a basal diet deficient in vit E and Se or the basal diet supplemented with Vit E, Se or Vit E and Se. Pigs were maintained on their respective diet for 25 d. Canine sera were collected from pups maintained on a deficient diet for 8 wk. Four dogs and 4 pigs maintained on a commercial diet were used as donors of peripheral blood lymphocytes (PBL). The addition of sera from pigs or dogs maintained on a vit E- and Se-deficient diet markedly suppressed both porcine and canine PBL response to mitogens. Porcine PBL blastogenesis was also suppressed when porcine or canine sera were added 8, 24 or 48 h after the beginning of the incubation period to culture containing 1% of fetal bovine serum (FBS). However, the suppressive effect caused by porcine sera was less severe than the one due to canine sera. Addition of 1% FBS in the cultures was sufficient to eliminate the suppression caused by the presence of sera from pigs fed a vit E- and Se-deficient diet. Other attempts to restore the lymphocyte response to mitogens by the addition of indomethacin, diethylcarbamazine or eicosatetraynoic acid, inhibitors of prostaglandin and/or leukotriene synthesis, were not successful. Because of the severe suppression caused by sera from animals maintained on a vit E- and Se-deficient diet on the in vitro response of lymphocytes to mitogenic stimulations, it is very important to take precautions to avoid such deficiency. In vivo suppression of immunocompetent cells to antigenic stimulations may impair the capacity of the host to control infections.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1993

Improvement of cytogenetic results in B-cell chronic lymphocytic leukemia using immuno-purified leukemic cells.

Cytogenetics of purified B lymphocytes and whole blood cultures were studied in 14 patients with B-CLL and fluorescence in situ hybridization (FISH) was performed on interphase cells in 12 of these cases in order to detect trisomy 12. Only one minor abnormal clone was found on whole blood cell cultures, clonal anomalies were found in a large proportion of mitoses of 6/14 cultures of purified B cells. FISH detected a trisomy 12 in a case, not found in whole blood cultures but found in 78% metaphases of cultures of purified B lymphocyte. This method may be as sensitive as FISH for the detection of trisomy 12 and improves the detection of clonal abnormalities in CLL.

Adult↗
PubMed1992

Intrauterine diagnosis and evolution of a cardiomyopathy in a fetus with Noonan's syndrome.

We report on a newborn infant with a typical form of Noonan's syndrome. Because of the presence of a fetal cystic hygroma and normal karyotype the diagnosis was suspected before birth. A progressive hypertrophic cardiomyopathy was also found following fetal echocardiographic scanning. We conclude that in addition to cystic hygroma with normal karyotype, the presence of functional or morphological evidence of myocardial abnormality should be included also as prenatal features of Noonan's syndrome.

Cardiomyopathy, Hypertrophic↗
PubMed1992

Cardiac two-dimensional imaging and reference values for blood flow velocities in the ovine fetus.

Since the ovine model is the most commonly used for foetal haemodynamic investigation it was felt important 1) to investigate the technical difficulties involved with ultrasound fetal cardiac imaging in this species and 2) to establish normal reference values for ovine cardiac and umbilical blood flow velocity measurements. Both two-dimensional and pulsed Doppler techniques were used for this assessment in 25 unsedated ewes. All morphological features described in human features to identify the ventricular cavities could be found in the ovine fetus with the two-dimensional echocardiogram. Specific differences included a flatten thorax as visualized from the lateral position, the mesocardial position of the heart, and a large left azygos vein behind the left atrium draining blood into a dilated coronary sinus. The mean peak velocities (cm/sec) of the early diastolic wave (E) and the atrial wave (A), along with their calculated ratio, were not statistically different between the two atrio-ventricular valves (E: 30.6 +/- 6.6, 31.2 +/- 6.1; A: 43.0 +/- 8.3, 41.6 +/- 8.0; E/A: .72, .76 for mitral and tricuspid valves respectively). A significant difference was observed between the acceleration times of the blood ejected into the aorta and the pulmonary artery, with the time interval being shorter in the pulmonary artery (Aorta: 0.052 +/- 0.011; Pulmonary artery: 0.037 +/- 0.009 s). A mean pulsatility index of the umbilical artery of 0.89 was recorded. The data recorded in this study should serve as a reference base for further non-invasive studies of the ovine foetal circulatory system using the ultrasound technique.

Animals↗
PubMed1991

Two cases of inherited triple deficiency in a large kindred with thrombotic diathesis and deficiencies of antithrombin III, heparin cofactor II, protein C and protein S.

Thirty-three subjects, belonging to a large family with functional antithrombin III (ATIII) deficiency (type IIa) and recurrent thromboembolism, were investigated for ATIII, heparin cofactor II (HCII), protein C (PC) and protein S (PS). We report the exceptional finding of two cases of triple deficiency: ATIII combined with HCII and PC in the first case aged 15 and ATIII combined with HCII and PS in the second case aged 27. Interestingly, both are asymptomatic thus far. Twenty-five other deficient members were found, among which seven are affected with a double deficiency. Totally, the results of our study show 38 deficiencies of four distinct antithrombotic protein: ATIII (n = 9), HCII (n = 9), PC (n = 7) or PS (n = 13). Two types of HCII deficiency were observed and type I PC deficiency was found. Functional PS deficiency was characterized by reduced levels of cofactor activity for activated PC. Our report demonstrates that combined deficiencies should be sought in a family already known to be deficient in one antithrombotic protein.

Adolescent↗
PubMed1991

In utero sonographic diagnosis of diaphragmatic hernia with hepatic protrusion into the pericardium mimicking an intrapericardial tumour.

A case of right-sided congenital diaphragmatic hernia was detected at 33 weeks of gestation. Fetal echocardiography revealed the presence of an intrapericardial mass (3.5 x 3 cm) localized at the right of the heart and surrounded by a massive pericardial effusion. This mass had the same echogenicity as the liver, with which it shared vascular channels. The diagnosis of right diaphragmatic hernia with protrusion of hepatic tissue into the pericardial sac and secondary pericardial effusion was made and confirmed after birth. In utero diagnosis of this anomaly enabled correct assessment of perinatal risk, and optimal fetal and infant management.

Adult↗
PubMed1991

Diastolic circulatory dynamics in the presence of elevated placental resistance and retrograde diastolic flow in the umbilical artery: a Doppler echographic study in lambs.

To evaluate the effects of elevated placental resistance on the diastolic blood flow in the main arteries of the fetus, placental resistance was mechanically increased in six exteriorized lambs. A string was inserted into the exposed section of the umbilical cord and placed around the veins isolating them from the arteries. Doppler flow velocities waveforms were measured by placing a lightweight acoustic bag on the umbilical cord. Placental resistance was increased by tightening the string until retrograde diastolic flow was observed in the umbilical artery. All measurements were obtained within 10 minutes. Heart rate, PO2, PCO2, and pH before umbilical vein compression were 177 +/- 24 beats/min, 16.4 +/- 1.8 mm Hg, 42.5 +/- 4 mm Hg, and 7.3 +/- 0.05, respectively, and 112 +/- 38 beats/min, 5.9 +/- 1.5 mm Hg, 56.6 +/- 7.0 mm Hg, and 7.2 +/- 0.05, respectively, after umbilical vein compression. The patterns of diastolic flow observed after compression were descending aorta, retrograde; aortic arch, retrograde; ascending aorta, bidirectional; cephalic aorta, forward, which were quite different from their respective baseline patterns. It is concluded that the appearance of reverse diastolic flow in the umbilical artery indicates that (1) the lowest vascular resistance in the fetal circulatory network is no longer at the placental but at the cerebral level, and (2) preplacental blood with low oxygen content from the descending aorta and pulmonary artery is being shifted toward the brain.

Animals↗