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Biomedical subjects

R Lefebvre

Publications and source records attributed to R Lefebvre.

At least 37 records · Page 2Linked to original sources

Influence of nebivolol on the cardiovascular hemodynamics during postural changes and isometric exercise.

Nebivolol (R67555), a drug with beta 1 receptor antagonizing properties, was administered once daily (5 mg) for 7 days in 10 healthy volunteers. The hemodynamic parameters were measured noninvasively during postural changes (supine, sitting, standing) and during isometric handgrip at 50% maximal voluntary contraction, before and 3, 8, and 23 hours after the first nebivolol intake of 5 mg; the same measurements were done 23 hours after the last intake. Nebivolol lowered arterial blood pressure acutely and chronically due to a decrease in heart rate and cardiac output. The stroke volume seemed to be preserved, while the total peripheral vascular resistance did not change. Nebivolol did not change the orthostatic responses, except that the absolute value was lowered. Nebivolol was unable to prevent the blood pressure increase during isometric handgrip. However, this blood pressure increase was obtained by an increase in the total peripheral vascular resistance and not by an increase in the cardiac output, as observed during control measurements before nebivolol intake.

Adrenergic beta-Antagonists↗

Human immunodeficiency virus-infected multinucleated histiocytes in oropharyngeal lymphoid tissues from two asymptomatic patients.

Human immunodeficiency virus (HIV)-infected multinucleated giant cells previously were detected only in the central nervous system of HIV-positive patients. Reported here are the first cases in which such infected cells were observed outside the central nervous system, in the oropharyngeal lymphoid tissues. Tonsils and adenoids were removed individually from two asymptomatic homosexual men. Follicular hyperplasia and many interfollicular multinucleated giant cells most often in contact with or in close proximity of the mucous membrane were seen. The latter were positive for lysozyme, alpha-1 anti-chymotrypsin, OKM1, and S-100 protein in accordance with a histiocytic origin. In situ hybridization with an HIV envelope-specific RNA probe demonstrated the presence of viral RNA in these multinucleated giant cells. These findings support the role of peripheral histiocytes as a primary virus reservoir early in the disease. They also underline the potential role of oropharyngeal tissue as a primary target in some cases.

Adult↗

Effects of diltiazem and atenolol on exercise performance in man.

The effects of diltiazem and atenolol on exercise performance were studied in 9 healthy and physically fit volunteers according to a double-blind cross-over design. All subjects performed, with an interval of 1 week, 3 exercise tests on a treadmill with stepwise increase of the workload until exhaustion. Two hours prior to each exercise test they received in a randomised order placebo, diltiazem 120 mg or atenolol 100 mg. Running time and VO2peak were not influenced by diltiazem, while running time was significantly reduced (-10%) after atenolol. The reduction of VO2peak (-9%) after atenolol did not reach statistical significance. Both diltiazem and atenolol significantly decreased heart rate at peak effort but the decrease was much more pronounced after atenolol (-52 b.min-1) than after diltiazem (-6 b.min-1). At submaximal level VO2 was not influenced by diltiazem, but significantly lowered (-6%) after atenolol. Submaximal heart rate was decreased and plasma lactate concentration was increased by both diltiazem and atenolol, but the effect of atenolol was more pronounced. The study shows that maximal work performance of young healthy subjects is not affected by diltiazem 120 mg, in contrast to atenolol 100 mg which decreases maximal work performance in the same subjects.

Adult↗

The dissolution rate and bioavailability of hydrochlorothiazide in pellet formulations.

The influence of non-active ingredients in the manufacture of pellets on in-vitro dissolution rate and on bioavailability of hydrochlorothiazide has been studied. Pellets were formulated using either microcrystalline cellulose or microcrystalline cellulose-carboxymethylcellulose sodium blends as matrix, and hydrochlorothiazide as the active ingredient. In-vitro drug release from the different pellet formulations was retarded in comparison to a conventional tablet formulation and was dependent on the nature of the non-active ingredient and, for the microcrystalline cellulose-carboxymethylcellulose sodium blend, of the dissolution medium. In-vivo bioavailability of both pellet formulations was low compared with that of the conventional tablet and the plasma concentration-time profiles did not suggest slow release.

Adult↗

[A theoretical model of the transition phase in human locomotion].

In this study we examine the bifurcation of the transition between walking and running. Beuter and Lalonde (1986) have conjectured that the pertinent parameters separating walking and running can be described by a cusp singularity (Thom, 1972). In this model, the unidimensional state space is characterized by support duration and the bidimensional parameter space is characterized by the subject's weight and speed. To test this model eight males walked and ran on a motor driven treadmill at an increasing or decreasing speed with or without additional loads corresponding to 0%, 7% and 14% of their body weight. Velocities corresponding to transitions between the two modes of locomotion indicate that on the average the walk-run transition occurs at higher speed than the run-walk transition illustrating an hysteresis effect. In addition, the average difference between the transitions decreases as the load increases [mean 0 = 0.235 m/s, +/- 0.09 m/s, mean 7 = 0.104 m/s, +/- 0.07 m/s and mean 14 = 0.041 m/s, +/- 0.06 m/s] corresponding to an F ratio of F = 2.72, 0.05 less than p less than 0.1. A comparison of the differences in transition velocity at 0% and 14% is statistically different (t = 2.8, p less than 0.025). These results tend to support the existence of an elementary cusp singularity separating the two locomotion modes and suggest that the mechanisms controlling these transitions can be described by a hysterisis cycle and a small number of parameters.

Adipose Tissue↗

[Spontaneous development of paralysis induced by equipotent doses of vecuronium, atracurium, fazadinium, pancuronium, gallamine and d-tubocurarine].

Thirty-six patients undergoing elective surgery were studied after obtaining their informed consent. They were randomly assigned to six series of six patients each. One hour before anaesthesia, all patients received 0.2 mg.kg-1 diazepam orally. After induction of anaesthesia with 1-1.5 mg.kg-1 methohexitone and 5 micrograms.kg-1 fentanyl, the patients were paralysed and ventilation was controlled manually (semi-open circuit; 50% N2O/50% O2). Each patient received a single dose of either 70 micrograms.kg-1 fazadinium, 70 micrograms.kg-1 pancuronium, 2,500 micrograms.kg-1 gallamine or 450 micrograms.kg-1 d-tubocurarine. Neuromuscular function was monitored by measuring the isometric contraction of the adductor pollicis muscle in response to supramaximal stimulations of the ulnar nerve at the wrist (square wave pulse of 0.2 ms duration at supramaximal intensity delivery at 0.1 Hz). Three parameters were measured: the time between the injection of the relaxant drug and recovery of the twitch height at 50% of its baseline (RT0-50); the time between the injection of the relaxant drug and recovery of the twitch height at 90% of its baseline (RT0-90); the time between the injection of the relaxant drug and recovery of the twitch height from 25 to 75% of its baseline (RT25-75). The values of the observed parameters were expressed in minutes (means +/- SEM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Unilateral nodular diabetic glomerulosclerosis: recurrence of an experiment of nature.

The case of a 60-year-old diabetic patient with a fully developed diabetic glomerulosclerosis in one kidney, but only ischemic lesions in the contralateral one, which was 'protected' by a renal artery stenosis, is presented. The only other report of such a peculiar observation was made by Berkman and Rifkin on a patient who died in 1940. Because of the rather high incidence of diabetes and of renal artery stenosis, the scarcity of this 'experiment of nature' is astonishing and can be barely explained by a precise timing of the two pathological conditions. Despite rather detailed information on the clinical and paraclinical evolution of the present patient, the exact sequence of events could not be determined with certitude. Both cases bring a strong support for the role of glomerular hyperperfusion-hypertension in the pathogenesis and evolution of diabetic nephropathy and provide a theoretical basis for the importance of keeping the arterial pressure low in diabetics.

Diabetes Mellitus, Type 2↗

Flow cytometry sorting of unlabelled epidermal Langerhans cells using forward and orthogonal light scatter properties.

A variety of techniques based on the presence of specific markers has been proposed to enrich Langerhans cells from epidermal cell suspensions. Computer analysis of multiparameter flow cytometry records involving forward angle and orthogonal scattered light and immunofluorescence of epidermal cells allowed us to determine the scattering properties of Langerhans cells. Unlabelled cells sorted according to these properties were shown to be Langerhans cells by electron microscopy and/or subsequent labelling by anti-HLA-DR monoclonal antibody. The relevance of this method is discussed to sorting viable Langerhans cells which may be used in functional studies and for establishing long-term culture.

Female↗

Pulmonary sarcoidosis: flow cytometry measurement of lung T cell activation.

Lung T cell activation is considered a major factor in the pathogenesis of pulmonary sarcoidosis. Our study was designed to investigate several parameters of T cell activation among blood and alveolar cell populations, including expression of HLA-DR or MLR antigens, increased cell size, and presence of dividing cells. Blood sampling and bronchoalveolar lavages were performed in 20 patients with pulmonary sarcoidosis. Cell populations were analyzed by flow cytometry using immunofluorescence labeling with monoclonal antibodies to lymphocyte differentiation or activation antigens. Cell types were identified by their light-scattering properties. Cell cycle analysis was done after staining with acridine orange. Bronchoalveolar lavage contained a higher proportion of small T4-positive lymphocytes, and large cells of the same phenotype were detected in three patients. T cells bearing HLA-DR antigens were detected in six of 14 bronchoalveolar lavage samples. A marked increased of MLR-positive cells was found in the peripheral blood of eight of eight patients and in the bronchoalveolar lavage of five of seven patients. Increased percentages of cells in the S + G2 + M phases were found in blood lymphocytes from three patients and in half the bronchoalveolar lavage samples. Therefore, a variety of activation markers may be expressed by alveolar T cells. Their qualitative and quantitative assessment may provide additional criteria for staging the intensity of the alveolitis, and the possible relationship between these markers and disease progression or activity deserves long-term clinical investigation.

Adult↗

Activated lung lymphocytes in hypersensitivity pneumonitis.

T-lymphocyte activation was investigated in peripheral blood and bronchoalveolar lavage (BAL) of four patients with hypersensitivity pneumonitis. The study was performed by flow cytometry with the use of immunofluorescence labeling with monoclonal antibodies to lymphocyte differentiation or activation antigens. Simultaneous measurement of DNA and RNA content by acridine orange staining was used for cell-cycle analysis. The various cell types were identified by their light-scattering properties. T cell activation was demonstrated in the BAL of all patients by the presence of T cells (OKT3 positive) bearing class II histocompatibility antigen (HLA-DR) and activated T cell markers (MLR 1-3). Lymphocyte proliferation was evidenced in BAL but not in blood of patients by an increased percentage of cells in S + (G2 + M) phases. In addition, T-lymphocyte subsets analysis revealed no abnormalities in the blood and no major imbalance in the BAL despite a slightly increased OKT4/OKT8 ratio. The finding of T cell activation and lymphocyte proliferation in hypersensitivity pneumonitis alveolitis is consistent with the contribution of a local type IV immune reaction to the pathogenesis of this disease.

Alveolar Process↗

Pulmonary hyalinizing granuloma: a cause of pulmonary nodules.

The radiological and histological appearance of pulmonary hyalinizing granuloma (PHG) and its pathogenesis are described. The histological features bear a striking resemblance to fibrosing mediastinitis. Patients present clinically with nonspecific respiratory or general symptoms. Slowly growing solitary or, more often, multiple nodules are found on radiographs of the chest, suggesting neoplastic disease. Four patients with PHG are described. Four patients with PHG are described. One had lesions in the kidneys that were pathologically identical to those of PHG. There is no clear etiology for this disease, but from the cases reported here and those reported previously it is postulated that diverse etiologic factors might lead to a common immunological response. Inflammatory agents such as tubercle bacilli or fungal organisms (e.g., Histoplasma), or a collagen or autoimmune disease may act as trigger mechanisms for the induction of PHG.

Adult↗

In vitro study of the influence of dopamine on rat and dog gastric fundus.

The effect of dopamine was studied in rat longitudinal fundus strips and in dog circular and longitudinal fundus strips. Contractions of similar amplitude were induced by transmural stimulation and by methacholine. In the rat, dopamine inhibits the electrically induced contractions partially by a post-junctional influence on the smooth muscle cells and partially by inhibiting the release of acetylcholine from the intramural cholinergic neurons. The latter effect is antagonized by phentolamine, while the former is antagonized by propranolol. Dopamine antagonists change the inhibitory effect of dopamine to a small degree but have a similar influence on the inhibitory effect of noradrenaline. The inhibitory effect of dopamine is largely indirect through the liberation of noradrenaline, since in the presence of cocaine or after reserpine-pretreatment the inhibition by dopamine is markedly reduced. In the presence of propranolol, cocaine and hydrocortisone, the inhibitory effect of dopamine is equally antagonized by the alpha 1-antagonist prazosin and the alpha 2-antagonist rauwolscine. In the dog, the inhibition of the electrically induced contractions by dopamine is mainly due to inhibition of the release of acetylcholine from the intramural cholinergic neurons. This effect is not influenced by the presence of cocaine and is completely antagonized by phentolamine and rauwolscine, while prazosin has no effect. From the dopamine antagonists tested, only metoclopramide had some antagonistic effect against dopamine but it antagonized to the same degree the inhibition by noradrenaline.

Animals↗