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Biomedical subjects

L Dubé

Publications and source records attributed to L Dubé.

30 records · Page 2Linked to original sources

Comparison of two administration techniques of inhaled nitric oxide on nitrogen dioxide production.

The purpose of this study was to verify whether, compared with the introduction of the NO-N2 mixture at the air inlet of the ventilator (classical method), a direct injection of NO-N2 into the inspiratory line of the ventilator circuit with a new injection device (new method), would reduce NO2 formation by reducing contact time between O2 and NO. The effect of two FIO2(0.21 and 0.90) and NO concentrations on NO2 production was determined. In the classical method, NO and O2 were mixed with an air/oxygen blender before the gas mixture entered the ventilator. In the new method, NO was injected directly into the respiratory line with the injection system. Nitric oxide and nitrogen dioxide gases were measured using a chemiluminescence analyzer. For a FI02 of 0.90 and 90 ppm of NO2, the amount of NO2 produced was decreased from 8.9 +/- 0.8 ppm (mean +/- SD) with the classical injection system to 4.4 +/- 0.2 ppm with the new injection system (P = 0.0039, Mann-Whitney test), and NO2 production was decreased from 4.5 +/-0.2 ppm to 2.1 +/- 0.4 ppm (P = 0.02) at 60 ppm of NO. However, at a FIO2, no difference was found in the amount of NO2 produced. We conclude that, compared with the classical method of NO administration, the new NO injection system reduces considerably the concentration of inhaled NO2 when a high FIO2 and a high concentration of NO are used.

Administration, Inhalation↗

Moderators and determinants of satisfaction with diet counseling for patients consuming a therapeutic diet.

OBJECTIVE: To identify moderators and key determinants of patient satisfaction with diet counseling. DESIGN: Survey questionnaire. SETTING: A French-Canadian acute-care urban hospital. SUBJECTS: Population of eligible patients hospitalized for a minimum stay of 5 days. Patients excluded from the study were those with notable physical, cognitive, or emotional limitations; those receiving enteral and parenteral nutrition; and those from long-term-care units. Analyses were performed on 49 patients who consumed a therapeutic diet and who received diet counseling during their current hospital stay. MAIN OUTCOME MEASURES: Overall satisfaction with diet counseling, compliance intentions, and satisfaction with four components of diet counseling. Measures were taken on seven-point graphic scales and five-point semantic scales. STATISTICAL ANALYSIS: Reliability estimates with Cronbach's alpha correlation coefficient, stepwise multiple regression analyses, t tests, and one-way analyses of variance. RESULTS: Facilitation skills and knowledge components of diet counseling were the key determinants of patient satisfaction. Among the moderators of patient satisfaction with diet counseling, women and patients with a good appetite were more satisfied with the knowledge components and had stronger compliance intentions. Patients who spent more than 50% of the time at rest were less satisfied than more active patients. APPLICATIONS: Enhancing patient satisfaction implies having a good understanding of a patient's social and cultural context, developing problem-solving skills, and demonstrating greater flexibility and creativity about the means of providing diet counseling.

Adolescent↗

Stereoselective metabolism of the 5-lipoxygenase inhibitor A-78773.

Based on the knowledge that glucuronidation was a major route of metabolism of the N-hydroxyurea class of 5-lipoxygenase inhibitors, a simple in vitro glucuronidation assay was established using liver microsomes from various species, including man. Compounds that were potent inhibitors of 5-LO and showed a reduced metabolic liability in vitro were then characterized more extensively in experimental animals. This prudent usage of in vitro glucuronidation proved to be highly efficient and was indispensable in the identification of A-78773, a potent new long-acting 5-LO inhibitor. Further studies with liver microsomes revealed that glucuronidation of A-78773 was stereoselective and that the R(+) enantiomer was considerably more resistant to conjugation than the S(-) stereoisomer. Pharmacokinetic studies in experimental animals and humans confirmed the greater metabolic stability of the R(+) enantiomer. A single 400-mg oral dose of A-78773 inhibited ex vivo leukotriene biosynthesis for more than 24 hours. Since 78% of the drug plasma AUC following A-78773 administration was accounted for by the R(+) enantiomer, it is reasonable to assume that the majority of the leukotriene inhibition caused by the racemate is attributable to the R(+) enantiomer, A-79175, particularly at the later times. The equivalent 5-lipoxygenase inhibitory potency coupled with the superior pharmacokinetic profile of the R(+) enantiomer, A79175, compared to the S(-) enantiomer, A-79176, indicate that the development of this compound may be preferable to the racemate A-78773.

Animals↗

Determining the complexity of patient satisfaction with foodservices.

OBJECTIVES: (a) To identify the psychological dimensions representing how patients perceive the quality of foodservice; (b) to identify which dimensions best explain variation in the satisfaction ratings of patients; and (c) to identify subgroups based on individual characteristics of patients and contextual factors. DESIGN: Survey questionnaire. SETTING: Patients of a specialized acute-care urban hospital in Canada. SUBJECTS: One hundred thirty-two hospitalized patients (minimum stay of 5 days) who had not received nutrition counseling. Subjects excluded from the study were patients with notable physical, cognitive, or emotional limitations; patients receiving enteral or parenteral nutrition; and patients from long-term-care units. MAIN OUTCOME MEASURE: Overall satisfaction with meals and with foodservices, and satisfaction with 26 specific foodservice attributes. STATISTICAL ANALYSIS: Factor analysis followed by orthogonal rotation (varimax), stepwise multiple regression analysis, and one-way analysis of variance. RESULTS: Seven dimensions represented patients' perceptions of foodservice: food quality, service timeliness, service reliability, food temperature, attitude of the staff who deliver menus, attitude of the staff who serve meals, and customization. Food quality was the best predictor of patient satisfaction with meals and foodservice, followed by customization and attitude of the staff who deliver menus. Individual characteristics (gender, age, education, perception of degree of control over health, and belief that food influences one's health status) and contextual factors (normal or therapeutic diet, time spent at rest, and appetite) influenced patient satisfaction. IMPLICATIONS: The results emphasize the need for a comprehensive and differentiated approach in measuring and monitoring patient satisfaction with foodservices.

Adolescent↗

Intravenous nifedipine to treat hypertension after coronary artery revascularization surgery. A comparison with sodium nitroprusside.

We administered sodium nitroprusside (SNP) or nifedipine intravenously to patients who became hypertensive after elective coronary revascularization and compared their effects on hemodynamics and the electrocardiogram in a parallel, randomized, open-label study. Four of 21 patients treated with nifedipine required the addition of SNP to maintain mean arterial pressure less than 90 mm Hg, compared with 4 of 28 patients in the SNP group who required the addition of nifedipine. The success rates of nifedipine (81%) and SNP (86%) were not significantly different. There was no difference in the incidence of adverse ST-segment changes during drug infusion (4% versus 5%) or perioperative myocardial infarction (9.5% versus 10.7%) in the nifedipine versus SNP groups, respectively. The plasma nifedipine concentration (mean value +/- SD) at steady state for 21 patients receiving nifedipine was 119 +/- 42.5 ng/mL. The pharmacokinetic variables for nifedipine were as follows (mean values +/- SD): systemic clearance, 0.525 +/- 0.228 L.h-1.kg-1; apparent volume of distribution, 0.738 +/- 0.446 L/kg; and elimination half-life, 1.02 +/- 0.51 h. These values are similar to those reported previously in healthy volunteers. We conclude that intravenous nifedipine can be used safely to control hypertension after coronary revascularization but were unable to demonstrate an advantage of nifedipine compared with SNP in preventing postoperative ischemia or infarction in this group of patients who had good left ventricular function.

Blood Pressure↗

Effect of Zileuton (A-64077) on the 5-lipoxygenase activity of human whole blood ex vivo.

The potency and reversibility of a new orally active 5-lipoxygenase (5-LO) inhibitor were evaluated in human volunteers. Zileuton (A-64077) 600 mg q.i.d. was administered to volunteers for 14 days in a phase I study, and blood samples were withdrawn, stimulated with ionophore A23187 and LTB4 levels were determined using both reverse phase high performance liquid chromatography (RP-HPLC) and radioimmunoassay (RIA). The drug significantly inhibited (above 70%) LTB4 biosynthesis in whole blood stimulated with A-23187 throughout the 14 days. The activity of 5-LO was also measured one week after stopping the medication and was returned to control levels. Measurement of LTB4 levels using either RP-HPLC or RIA gave similar percentage of inhibition although RIA appeared to underestimate by half the absolute amounts of LTB4 in the blood samples. These results show that Zileuton is a highly active and reversible 5-LO inhibitor in human.

Adolescent↗

Pharmacokinetics, safety, and ability to diminish leukotriene synthesis by zileuton, an inhibitor of 5-lipoxygenase.

Zileuton is a potent and specific inhibitor of 5-lipoxygenase, the first dedicated enzyme in the metabolism of arachidonic acid to the leukotrienes. The leukotrienes have been implicated in numerous pathological conditions. Zileuton was given to normal human volunteers in single doses of 200 mg to 800 mg. Results of these studies indicated that zileuton was well absorbed orally with an elimination half-life of approximately 2.5 hours. Leukotriene B4 production by ex vivo calcium ionophone stimulated whole blood was inhibited by up to 80% of baseline and correlated with plasma concentrations. Zileuton did not significantly inhibit cyclooxygenase as demonstrated by thromboxane B2 levels. There were no safety concerns that would preclude development.

Adolescent↗

Hypotonic shock activates a maxi K+ channel in primary cultured proximal tubule cells.

The nature and function of the ionic channels at the apical membrane of primary cultured proximal tubule cells (PT) was investigated by use of the extracellular patch-clamp method. Several types of ionic channels were observed, including a calcium-dependent K+ channel of 206 pS in symmetrical 162 mM KCl activated at depolarizing potentials [maxi K+(Ca2+)]. Whole cell experiments were also carried out that clearly indicated that the PT cells respond to a hypotonic shock by activating electroconductive pathways. This response consisted of an initial hyperpolarization (from -47 to -58 mV, SD = 3, n = 4), followed by a strong depolarization (to -23 mV, SD = 4, n = 4). Furthermore, it was found in cell-attached experiments that the maxi K+(Ca2+) channel becomes activated during the hypotonic challenge. The activation process required external Ca2+, although some residual single-channel activity was measured in the absence of extracellular calcium (n = 3). On the basis of these results, it is concluded that the volume regulation process in PT cells in response to a hypotonic shock involves an influx of calcium from the external medium, which in turn triggers the opening of apical maxi K+(Ca2+) channels.

Animals↗

Striatal afferents in the newt Triturus cristatus.

In order to investigate the neuronal populations projecting to the corpus striatum in the brain of a urodele, Triturus cristatus, horseradish peroxidase (HRP) retrograde labeling was used in parallel with anterograde degeneration, glyoxylic acid histofluorescence and behavioral testing. Striatal injections of HRP revealed that the main striatal afferent systems originate within the diencephalon, specifically in the dorsal thalamus and paraventricular organ of the hypothalamus. Several small groups of neurons in other diencephalic areas also participate in striatal innervation: proeminentia ventralis, amygdala, contralateral corpus striatum, preoptic area, posterior tuberal nucleus, locus coeruleus and raphe nuclei. Degeneration experiments after mechanical lesion of the paraventricular organ established the existence of a hypothalamostriatal projection. Degenerating axonal profiles were also found in many of the structures already identified as projecting to the striatum, suggesting that the paraventricular organ might influence the striatum not only directly but also indirectly through these other afferent systems. In the paraventricular organ, glyoxylic acid fluorescence histochemistry showed numerous monoamine neurons that corresponded in distribution and morphology to the retrogradely HRP-labeled neurons. Paraventricular-organ-lesioned males displayed a severe impairment of courtship behavior in the form of decreased tail beating and head stepping by the females. This suggests that the regulation of stereotyped hypermotricity might involve the monoamine component of the hypothalamo-striatal projection.

Afferent Pathways↗

Identification of synaptic terminals of thalamic or cortical origin in contact with distinct medium-size spiny neurons in the rat neostriatum.

In order to determine what types of neurons in the striatum receive direct synaptic input from corticostriatal and thalamostriatal fibres and whether these afferents converge on individual striatal neurons, double anterograde labelling of axon terminals was combined with Golgi impregnation at both the light and electron microscopic levels. The area of the central neostriatum that receives input from both the parafascicular nucleus of the thalamus and the somatosensory cortex was identified by retrograde transport of a conjugate of horseradish peroxidase and wheat germ agglutinin (HRP-WGA). The same region of the neostriatum was studied in rats that had received multiple electrolytic lesions in the somatosensory cortex and also an injection of HRP-WGA in different parts of the parafascicular nucleus. Sections of this part of the neostriatum were impregnated by the single-section Golgi procedure after revealing anterogradely transported HRP-WGA. Twelve Golgi-impregnated spiny neurons were recovered and examined in the light and electron microscope after gold-toning. Ten of these neurons were typical very densely spiny medium-size neurons and they were all found to receive asymmetric synaptic input on dendritic spines from degenerating corticostriatal boutons. However, even though numerous boutons labelled anterogradely by HRP-WGA from the parafascicular nucleus were found within the dendritic fields of neurons that received cortical input, none of the terminals from the thalamus made synaptic contact with these neurons. Instead, all 96 thalamostriatal boutons studied were found in asymmetric synaptic contact with dendritic shafts of other neurons. Two such neurons that received input from the parafascicular nucleus were Golgi-impregnated and appeared to be medium-size spiny neurons, but they had a lower density of spines than the typical very densely spiny neurons. An independent confirmation that the targets of thalamostriatal neurons originating in the parafascicular nucleus are dendritic shafts was provided by studying the boutons labelled following electrolytic lesioning or injection of the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) into this nucleus: these boutons were also found to form asymmetric synaptic contacts with dendritic shafts within the neostriatum. It is concluded that although afferents from the somatosensory cortex and from the parafascicular nucleus converge upon the same part of the neostriatum, they probably do not converge upon the same spiny neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The monoamine-containing neurons in avian brain: I. A study of the brain stem of the chicken (Gallus domesticus) by means of fluorescence and acetylcholinesterase histochemistry.

The distribution of monoamine (MA)-containing nerve cell bodies in the brain stem of the chicken (Gallus domesticus) was studied by means of paraformaldehyde and glyoxylic acid fluorescent histochemical methods. The MA neurons were further characterized morphologically and histochemically in material prepared for the demonstration of acetylcholinesterase (AChE). In the rostral midbrain of the chicken, two large collections of catecholamine (CA)-containing cells are found: one located in the ventromedial and the other in the dorsolateral (pedunculopontine nucleus) portions of the tegmentum. On the basis of their topographic location, CA content, and fiber connections, these ventromedial and dorsolateral cell groups can be tentatively associated with the CA-containing neuronal populations of the mammalian ventral tegmental area and pars compacta of the substantia nigra, respectively. In the caudal midbrain of the chicken, numerous CA-containing cells are intermingled with serotonin (5HT)-containing perikarya beneath as well as within the decussation of the superior cerebellar peduncles. At isthmus levels, abundant, closely-packed CA-containing cells are encountered along the lateral border of the central gray. These neurons, which display a very high AChE activity, appear to be equivalent to those of the mammalian locus coeruleus. A multitude of medium-sized 5HT-containing neuronal somata occurs within the raphe region of the isthmus. Some of these somata closely surround the medial longitudinal fasciculus. This 5HT-containing cell group also massively invades the lateral tegmentum, where it becomes closely intermingled with the CA-containing neurons of the locus coeruleus and subcoeruleus. All of these 5 HT-containing neurons display a moderate to high AChE activity. In the medulla the number of MA-containing neurons is much smaller than in the upper brain stem. Nevertheless, 5HT-containing cells are present within the raphe region, particularly in the upper two-thirds of the medulla, and CA-containing perikarya can be found along the lateral border of the medulla and within the confines of the nucleus solitarius. The findings of the present study reveal that the MA-containing neuronal systems in the avian brain stem are organized according to a pattern that is much more complex than the one disclosed in reptiles or in other nonmammalian vertebrates. This complexity arises in large part from the fact that the 5HT-containing systems undergo a prominent lateralization in birds, which leads to a close intermingling of 5HT-containing and CA-containing neuronal elements at various levels of the neuraxis.

Acetylcholinesterase↗