Biomedical subjects

P Lapalus

Publications and source records attributed to P Lapalus.

At least 37 records · Page 2Linked to original sources

PubMed1992

Placebo effect in cardiovascular clinical pharmacology.

A placebo is a pharmacologically inactive substance that can have a therapeutic effect if administered to a patient who believes that he or she is receiving an effective treatment. It is generally admitted that the placebo effect decreases blood pressure in 20% to 30%, when evaluated by casual sphygmomanometer or ambulatory systems. In order to evaluate the occurrence of a placebo effect in cardiovascular pharmacology, we analysed two studies. One study included ten mild-to-moderate hypertensive patients, and consisted of two submaximal exercise tests separated by a single oral administration of the placebo. The other study included six healthy volunteers, receiving an oral placebo during ten days. The placebo was in both case presented as an effective antihypertensive agent. Any change on blood pressure and heart rate, both at rest and during exercise, was observed before and three hours after the placebo. After ten days of placebo administration, no statistically significant change in blood pressure or heart rate was obtained. Nor was any statistical difference observed in catecholamine plasma levels, either three hours or ten days after oral administration of the placebo. The second study did not show any evidence of changes in lymphocytic beta-adrenoceptor density after ten days of placebo. The results of these pilot studies suggest that the use of a placebo group in cardiovascular clinical pharmacology should be reconsidered. The real occurrence and characteristics of a placebo effect should be evaluated by a complementary study.

Blood Pressure↗

PubMed1992

Acute arsenic intoxication: forensic and toxicologic aspects (an observation).

The authors report on an acute suicidal arsenic intoxication (di-arsenic-trioxide). Death can occur one week after ingestion, despite intensive care. The forensic, anatomopathological and toxicologic aspects are reported. Forty titrations are realized at the level of the biologic fluid in viscera, by absorption spectrophotometry. These data are compared with those in standing literature, especially with the rates determined in normal subjects, following simple environmental impregnation.

Adult↗

PubMed1992

[Gingival hyperplasia secondary to the use of calcium antagonists: analysis].

Calcium antagonists are drugs restricting transmembrane calcium delivery. They possess a wide range of action against vasoconstriction and spastic reactions and were therefore initially recommended for the treatment of angina pectoris. With the increasing number and classes of calcium antagonists new therapeutic indications have emerged. Cases of gingival hyperplasia associated with their use are repeatedly reported, therefore the question deserves to be restated. The aim of the present study was to discuss the clinical, pathologic and pathogenetic features bases on an investigation carried out in a Department of Cardiology, on a case observation and on review of published cases in the international literature.

Adult↗

PubMed1991

[Changes in plasma histamine and catecholamines levels after injection of chymopapain in chemonucleolysis].

Because pruritus, erythema and tachycardia are observed in some patients during chemonucleolysis, a prospective study was designed to investigate the plasma levels of histamine and catecholamines occurring after an injection of chymopapain. Thirteen patients (11 men and 2 women), mean age 38 +/- 11 years, were studied. They all had negative prick skin tests, human basophil degranulation tests (HBDT) and radio-absorbent tests (RAST) to chymopapain. The patients were premedicated with 100 mg hydroxyzine and 3 g tranexamic acid. Sedation was carried out using 0.1 mg.kg-1 droperidol and 0.02 mg.kg-1 phenoperidine. The nucleosus pulposus was visualized with 3 ml of contrast medium (lopamiron 300); 2 ml of chymopapain were then injected. Blood samples were obtained at T1 (after the contrast medium, but before the chymopapain), and then 5, 10, 15, 20 and 30 minutes after the chymopapain. The usual haemodynamic parameters were recorded at the same times. Four patients had clinical signs (group I), whereas the other nine (group II) did not. There was an increase in histamine levels in three patients from group 1, as well as in two in group II (up to 33 nmol.l-1). However, mean histamine and catecholamines levels were comparable in both groups at all times, and between times, of sampling. There therefore was no relationship between clinical signs and the release of histamine or catecholamines. The premedication with an antihistamine may have protected the patients, but the signs reported by four patients may also be due to the chymopapain itself.

Adult↗

PubMed1991

Influence of beta-blockade on circulating plasma levels of 3-methoxy-4-hydroxy phenylethylene glycol (MHPG) during exercise in moderate hypertension.

1. The effect of exercise testing and beta-blockade on plasma norepinephrine (PNE), and secretion of its metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), was assessed in 28 mild-to-moderate hypertensives before and after the administration of dilevalol, a new beta-blocker with beta 2-agonism. 2. This double blind, placebo-controlled study consisted of two successive submaximal exercise tests before and after the administration of a single oral dose of dilevalol (200 mg, 400 mg or 600 mg). Plasma norepinephrine levels were determined at rest, at 100 watts step of exercise and at maximal effort (Emax). 3. During the control test, mean PNE levels increased from 1.73 +/- 0.52 nmol/L (resting value) to 8.01 +/- 4.01 nmol/L at Emax (P less than 0.01) as MHPG levels increased from 11.18 +/- 1.33 nmol/L (rest) to 17.50 +/- 1.15 nmol/L (Emax, P less than 0.01). After dilevalol, PNE increased significantly as compared to controls (P less than 0.05), from 2.32 +/- 0.99 to 12.42 +/- 5.97 nmol/L (P less than 0.01). PNE and MHPG levels were correlated, both at rest and during exercise. PNE levels after beta-blockade were linearly related to the dose of beta-blocker administered. MHPG levels were unaltered by the administration of dilevalol, both before and after exercise. 4. The increase in MHPG that occurs during bicycle exercise is largely generated from an increase in central nervous system noradrenergic activity. While dilevalol increases the peripheral sympathetic nervous system, both at rest and during exercise (which is reflected by increases in PNE levels) the drug does not alter resting central nervous system noradrenergic activity nor amplify the increase in central noradrenergic activity that occurs during exercise.

Adrenergic beta-Antagonists↗

PubMed1991

In vitro and in vivo ciprofloxacin pharmacokinetics in human neutrophils.

Early in vitro investigations have shown that ciprofloxacin is concentrated within human neutrophils (polymorphonuclear leukocytes [PMNs]) at between 3 and 11 times the extracellular concentration. The elution of ciprofloxacin from cells is relatively rapid when the extracellular concentration is reduced. In order to estimate the in vivo intracellular penetration of ciprofloxacin and to determine its intracellular pharmacokinetics, PMNs were recovered from blood samples drawn from healthy volunteers at different times during a 24-h period after they were given a 750-mg oral dose. High-performance liquid chromatographic determination of ciprofloxacin in serum and cells showed that the intracellular/serum ratio was 3.7 at 1.5 h (maximum concentration of drug in serum), 5.7 at 12 h, and 20 at 24 h. The area under the curve ratio was 3.73. The mean elimination half-lives of ciprofloxacin were 3.7 and 6.2 h in serum and PMNs, respectively. These data show that in vivo findings are in agreement with in vitro findings. The large uptake of ciprofloxacin by PMNs combined with a prolonged intracellular half-life described under the conditions of human therapy should provide the basis for the use of ciprofloxacin in infections caused by susceptible intracellular bacteria.

Adult↗

PubMed1991

Acidic FGF and other growth factors in preretinal membranes from patients with diabetic retinopathy and proliferative vitreoretinopathy.

The development and extension of fibrovascular or fibroglial membranes onto the retinal surface are a major cause of visual loss in diabetic patients with proliferative retinopathy and in patients suffering from retinal detachment with proliferative vitreoretinopathy. The pathogenesis of these proliferative diseases, however, remain poorly understood and the nature of growth-promoting mediators implicated in these phenomena has not been determined yet. Using indirect immunofluorescence procedures, three different growth factors known to be mitogenic for various cell components of preretinal membranes, acidic fibroblast growth factor, epidermal growth factor and insulin-like growth factor type I, were sought in 14 specimens of preretinal proliferative tissues. Similar results were obtained in diabetic preretinal membranes and tissues from patients with proliferative vitreoretinopathy. The three different growth factors were found diffusely in the connective stroma and around new blood vessels within the vascular walls. Some fibroblast-like and pigment epithelial-derived cells more markedly reacted with anti-growth factor antibodies. These results provide indications on the eventual involvement of three potent growth factors in intraocular proliferative diseases, but whether or not these mediators play an active role in the development of preretinal membranes remains to be determined.

Adult↗

PubMed1991

[Comparative efficacy of sustained release verapamil and captopril in mild to moderate arterial hypertension by ambulatory measurement and occasional measurement].

The evaluation of mild to moderate hypertension must be carried out under the conditions in which treatments are usually prescribed, i.e., in general practice. After specific training of the physicians in the methods used, we evaluated the efficacy and safety of a new formulation of verapamil by comparing it with a reference drug: captopril. The main assessment criterion was the restoration of normal blood pressure in mildly to moderately hypertensive patients (blood pressure in excess of 160/95 mmHg). Blood pressure was evaluated by two methods: a mercury column sphygmomanometer, after the patient had rested in a half-sitting position for 10 minutes, and the ambulatory measurement of blood pressure (AMBP) using the SpaceLabs system. The results of this study involving 40 patients followed up for 3 months by 8 GPs in collaboration with our blood pressure unit were as follows: on verapamil, 47% of patients recovered normal values after 30 days of treatment and 71% after 60 days (with no change in dosage). On captopril, the normalization rates were 22 and 27% respectively. The highly significant reduction of blood pressure found by the "occasional" measurement for both treatments (p less than 0.001) was only faintly reflected by AMBP. Verapamil induced a reduction of nighttime blood pressure with no significant impact on heart rate. The clinical, paraclinical and electrocardiographic safety of both treatments was good.

Adult↗

PubMed1991

[Immunomorphological study of the vitreous body and subretinal fluid in vitreoretinal proliferation].

Proliferative vitreoretinopathy (PVR) is a major complication of rhegmatogenous retinal detachment. Its pathogenesis remains poorly understood and the accurate nature of the growing cells on both surfaces of the detached retina has not been yet determined. We undertook an immunocytological study on 28 specimens of vitreous or subretinal fluid removed from patients with PVR. Five main types of cells could be identified: heavily pigmented cells, poorly pigmented ones, large totally unpigmented macrophage-like ones, smaller unpigmented cells and lymphocytes. Analysis of intravitreal pigment granules showed two different types of pigmented cells, those with lipofuscin and melanin and those with melanin without any granules of lipofuscin, which could originate from ciliary or iris pigment epithelia. Immunostaining procedures confirmed the epithelial non macrophagic lineage of the intravitreal and subretinal cells. Lymphocytes were only B cells. These results confirm the importance of proliferative process during the course of PVR and shows the involvement of other ocular structures other than the retinal pigment epithelium.

Aqueous Humor↗

PubMed1991

Clinical and biological evaluation of dilevalol vasodilating properties in mild to moderate hypertension.

Dilevalol is a vasodilating beta-blocker with proven antihypertensive activity. In this study, 28 patients with mild-to-moderate uncomplicated hypertension underwent 2 submaximal exercise tests, each consisting of progressive steps of 20 watts for 2 minutes or up to 85% theoretical maximum heart rate. Five minutes after the first test, patients received either placebo or dilevalol 200 mg, 400 mg or 600 mg. The second exercise test was performed 3 hours later. Diastolic blood pressure, systolic blood pressure, heart rate and norepinephrine plasma levels were assessed before and after exercise. Dilevalol at all doses caused a significant decrease in heart rate and blood pressure both at rest and during exercise, compared to placebo. Dilevalol 600 mg had a greater effect on diastolic blood pressure than dilevalol 200 mg and 400 mg. Administration of dilevalol 200 mg and 400 mg enabled 42% of patients to increase their maximal exercise level by 20 to 60 watts. Dilevalol increased plasma norepinephrine levels at the 100 watts exercise levels from 5.1 +/- 4.0 nmol/l to 7.6 +/- 4.3 nmol/l (p less than 0.05). No adverse effects were observed during dilevalol treatment. This study shows that dilevalol is an effective antihypertensive agent that blunts heart rate and blood pressure risings during exercise.

Administration, Oral↗

PubMed1991

Lack of placebo effect in exercise response of hypertensive patients.

UNLABELLED: The administration of placebo (a pharmacologically inactive substance) is justified in clinical trials of antihypertensive drugs in order to exclude the placebo effect. The evaluation of antihypertensive treatments during exercise is an interesting end point, since aerobic exercise is part of antihypertensive treatment. The aim of this study is to determine the placebo effect on blood pressure, heart rate and catecholamine secretion profiles during exercise testing. METHOD: 10 patients with untreated mild to moderate essential hypertension participated in a single blind study consisting of two successive submaximal exercise tests (85% of maximal predicted heart rate), separated by a single oral administration of placebo. Blood pressure and heart rate were measured after 10 minutes of rest and at the end of each effort step (2 min, 20 Watts), both before and after placebo. Blood samples (5 ml) were collected at rest and during maximal exercise before and after placebo, in order to determine the effect of placebo on circulating catecholamines. RESULTS: There were no significant difference between the "control" and after placebo exercise tests, neither in blood pressure or heart rate profiles, nor in values of circulating catecholamines (noradrenaline at rest: 1.88 +/- 0.96, effort: 6.43 +/- 1.93 nm/l before placebo, 1.65 +/- 0.83 nm/l and 5.71 +/- 2.12 nm/l after placebo respectively [NS]). CONCLUSION: The placebo effect, which is generally determined from blood pressure at rest by sphygmomanometry, seems devoid of any influence on blood pressure, heart rate or catecholamine profiles during exercise in patients with mild to moderate essential hypertension. Thus, antihypertensive treatments can be evaluated during exercise by comparison to baseline cardiovascular parameters without need of a placebo group.

Adult↗

PubMed1991

Class II histocompatibility antigen expression by cellular components of vitreous and subretinal fluid in proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is the major cause of failure in retinal detachment surgery. It is characterized by the formation of membranes extending along both surfaces of the detached retina and within the vitreous, but the nature of the growing cells has not yet been determined. Using cytologic and immunocytologic procedures with 13 different monoclonal antibodies directed against Class II histocompatibility antigens and various markers of epithelial and immunocompetent cells, 30 specimens were studied of vitreous or subretinal fluid removed from patients with PVR. Five main types of cells could be identified: heavily pigmented cells, poorly pigmented ones, large totally unpigmented macrophage-resembling ones, smaller unpigmented cells, and lymphocytes. Analysis of intravitreal pigment granules, using autofluorescence by epiillumination and cytologic procedures, showed two different populations of pigmented cells: one with autofluorescent lipofuscin granules and the other with exclusively melanin pigment. Immunostaining procedures confirmed the epithelial nonmacrophage lineage of the intravitreal and subretinal cells because most of these cells were positive for cytokeratin but negative for macrophage markers. In addition, 40-100% of these epithelial-derived cells strongly expressed Class II histocompatibility antigens HLA-DR and -DQ. Lymphocytes were found in 13 specimens; B-cells were seen, but no T-lymphocytes could be identified. These results confirm the involvement of retinal pigment epithelial cells and the strong morphologic changes they undergo during the course of PVR. Moreover, the expression of Class II histocompatibility antigens by the growing cells may be related to inflammatory phenomena, but their eventual role in the development and the extension of periretinal proliferation has not been determined.

Adolescent↗

PubMed1990

Immunohistologic study of epiretinal membranes in proliferative vitreoretinopathy.

We performed an immunohistologic study on 11 specimens of epiretinal membranes surgically obtained from patients who had rhegmatogenous retinal detachment with proliferative vitreoretinopathy. Immunostaining procedures were used to identify immunoglobulin and complement deposits, to visualize class II antigen expression by proliferating cells, and to determine eventual infiltration by cells of the immune system. Diffuse deposits of IgG, IgA, IgE, C1q, C3c, and C3d were found in epiretinal membranes, whereas numerous cells, including glial or pigmented epithelial cells, expressed HLA-DR and HLA-DQ antigens. Some macrophages and B or T8 lymphocytes were identified. These results suggest activation of the immune system during the course of proliferative vitreoretinopathy. Class II antigen expression could be dependent upon growth-promoting factors and interferon gamma and could play a crucial role in this immune reaction, which resulted in immunoglobulin deposition and activation of complement. However, the eventual role of immune phenomena in the extension of proliferative processes remains to be determined.

Adult↗

PubMed1990

Autoradiographic localization of D1 and D2 dopamine binding sites in the human retina.

The localization of dopamine binding sites was studied by in vitro autoradiography in the normal human retina using [125I]SCH 23982 for D1 receptor labelling and [125I]iodosulpride for D2 receptors. Results demonstrated that both types of binding sites were present in human retina. Binding of [125I]SCH 23982 to D1 dopamine receptor was blocked by 1 microM SKF 38393, SCH 23390 (D1 specific compounds) whereas bromocriptine and domperidone (D2 specific compounds) were inactive at the same concentration. On the contrary, binding of [125I]iodosulpride to D2 dopamine receptor was inhibited only by D2 drugs. Precise cellular distribution was given by microautoradiographic techniques and showed that binding sites were exclusively localized to the plexiform layers.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1990

Effects of short-term administration of dobutamine on left ventricular performance, exercise capacity, norepinephrine levels, and lymphocyte adrenergic receptor density in congestive heart failure.

This study was designed to determine the feasibility of identifying those patients with chronic heart failure who will be improved by dobutamine infusion. Twenty-two patients with stable heart failure were treated by infusion of an average dobutamine dose of 12.5 ng/kg/min for 36 hours, then again during a 4-hour session once a week for 1 month. Patients were evaluated by clinical, ergometric, and biochemical parameters (plasma norepinephrine and lymphocyte beta-receptor density) before and after every infusion. Hemodynamics were assessed before and during the first dobutamine infusion. A test with isoproterenol was performed prior to the start of dobutamine therapy. All patients exhibited hemodynamic improvement, which peaked at the 12th hour (55% increase in the cardiac index [p less than 0.01]; 35% reduction in the filling pressure and systemic arterial resistance). Five patients stopped the study prematurely. Nine patients (group 1) were clinically improved according to their NYHA classification. Eight patients (group 2) remained stable or had progressive disease. The lymphocyte beta-receptor density before dobutamine infusion was significantly higher in group 1 than in group 2 (66 +/- 12 vs. 46.7 +/- 18 fM/mg; p less than 0.01). Finally, a good correlation (p less than 0.05) was observed between the beta-receptor level and the isoproterenol dose required to obtain a heart rate of 130 beats/min.

Dobutamine↗

PubMed1990

HLA DR and DQ expression on human retinal pigment epithelial cells in vitro.

In a previous immunohistopathological study, we demonstrated a deviant expression of class II antigens on the uveal pigment epithelial cells of patients with proliferative diabetic retinopathy. The mechanisms triggering this abnormal expression by epithelial cells are not well known, and we tried to induce this phenomenon on primary cultures of human retinal pigment epithelial (RPE) cells. Confluent RPE-cell monolayers were supplemented with several biological or chemical reagents [recombinant interferon gamma, phytohemagglutinin A-P (PHA-P), phorbol-myristate acetate (PMA), recombinant interleukin-2, fibroblast growth factor (FGF), Insulin], to investigate their ability to induce HLA DR and DQ expression. On days 1, 3 and 5 after stimulation, the cells were incubated with monoclonal antibodies directed against human class II antigens: all reagents used failed to induce class II antigen: all reagents used failed to induce class II antigen expression. However, on day 7, we demonstrated the presence of numerous positive HLA DR and HLA DQ cells stimulated by gamma interferon, the percentages being closely related to the dose of this lymphokine. These findings, together with those of other investigators and our previous work on uveal pigmented epithelial cells in diabetic patients, may shed light on the exact implication of RPE in many poorly documented ocular diseases.

Aged↗

PubMed1990

Post mortem kinetics of secobarbital.

Post-mortem changes in barbiturate concentrations were evidenced using a rat-secobarbital model. The method used for the extraction and HPLC assay of barbiturates is suitable for all biologic fluids and post-mortem tissues. Kinetic data obtained is of excellent quality. Various modelization constants were defined. This experimental work emphasizes the difficulty of post-mortem toxicology, as concentrations found at the time of autopsy may be different from concentrations at the time of death, in blood as well as in tissues.

Animals↗

PubMed1990

Beta adrenergic binding sites in the human eye: an autoradiographic study.

Beta adrenergic binding sites were localized and characterized in the human eye by means of "in vitro" autoradiography, using [125I] (-) iodocyanopindolol (125ICYP) as radioligand. Binding sites were visualized by apposition of isotope sensitive film to slide mounted eye sections. Receptor sites were present in the extraocular muscles, in the conjunctiva, in the epithelium and endothelium of the cornea, in the trabeculum and in the ciliary muscle. They were also present in the lens epithelium and in the retina. The pigmented ocular structures were heavily labelled but the binding was nonspecific. Characterization of these binding sites was achieved by testing the ability of selective adrenergic compounds to displace 125ICYP binding. These studies suggested that the majority of adrenergic binding sites in nonpigmented structures of human eye were of a beta2 type.

Aged↗