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Biomedical subjects

J De Cree

Publications and source records attributed to J De Cree.

At least 19 recordsLinked to original sources
PubMed1993

The effect of a combined administration of ridogrel and ketanserin in patients with intermittent claudication.

After a 1-month placebo run-in phase, 27 patients with proven peripheral arterial obstructive disease participated in a double blind placebo controlled study and were divided in 3 groups, receiving either placebo, ridogrel 300 mg b.i.d. (a combined thromboxane synthase and receptor blocking agent) or a combination of ridogrel 300 mg b.i.d. and ketanserin 20 mg t.i.d. (a 5-HT2 serotonergic receptor antagonist) for a period of 1 month. In both active treatment groups, serum levels of thromboxane B2 decreased significantly to 3% of baseline. The levels of 6-keto-prostaglandin F1 alpha and prostaglandin F2 alpha increased two- to three-fold and levels of prostaglandin E2 6 times. Platelet aggregation induced by collagen and by U 46619, a thromboxane A2 mimetic, were significantly inhibited by both treatment regimen. Template bleeding times were significantly prolonged but plasma fibrinogen levels and the activated partial thromboplastin time were not affected with the active treatments. No such changes were seen with placebo. An inhibition of the serotonin-induced platelet aggregation was only seen in the ketanserin-treated group. In a 3-month open follow-up period during combined treatment with ridogrel and ketanserin in 22 patients, the effects on platelet function and prostanoids were maintained. The total duration of the walking distance on a treadmill improved significantly from 323 +/- 53 seconds to 399 +/- 48 seconds and the onset of claudication pain improved significantly from 121 +/- 29 seconds to 212 +/- 44 seconds, whereas the maximal drop of the post-exercise ankle/arm pressure gradient markedly and significantly improved from a control value of 0.38 +/- 0.05 to 0.51 +/- 0.05. These findings suggest that a combination of ridogrel and ketanserin may be of therapeutic value in the treatment of intermittent claudication.

Aged↗
PubMed1992

Comparative cardiac haemodynamics of bisoprolol, celiprolol, carvedilol and nebivolol in normal volunteers.

Nebivolol is a novel selective beta 1-adrenergic antagonist with an unusual haemodynamic profile. It improves left ventricular function in normals and in patients with a damaged left ventricle. We compared the cardiac effects of a 14-day treatment period with 10 mg o.d. of bisoprolol, 400 mg o.d. of celiprolol, 25 mg o.d. of carvedilol and 5 mg o.d. of nebivolol in a placebo-controlled crossover study in 7 volunteers with a mean age of 39 (range 30-53) years. Cardiac haemodynamics were assessed serially by means of systolic time intervals. The ratio of the preejection period to the left ventricular ejection time (PEP/LVET) was used as a indirect measure of left ventricular performance. The results show that the PEP/LVET is a very sensitive and reproducible index of left ventricular function. During treatment with placebo and bisoprolol no changes occurred; during treatment with celiprolol and carvedilol a significant but transient decrease of PEP/LVET occurred, and only during treatment with nebivolol a long-lasting and significant decrease of PEP/LVET occurred. With bisoprolol an increase of PEP and QS2c (total electromechanical systole) was observed, indicative of a negative inotropic effect. In conclusion, nebivolol, in contrast with both classical and vasodilating beta-blocking agents, substantially improves left ventricular function, possibly due to an improvement of diastolic function and left ventricular compliance, which may be of therapeutical value in the treatment of congestive heart failure.

Adrenergic beta-Antagonists↗
PubMed1988

Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist.

The pharmacological profile of nebivolol (N), a chemically novel beta-adrenergic antagonist, was assessed in investigations on isolated tissues, awake spontaneously hypertensive rats (SHR), closed-chest anesthetized dogs, and humans. In vitro, N was found to be a potent antagonist of beta 1-adrenergic receptors (A2 value, 5.8 X 10(-9) M) and only a weak beta 2-adrenergic antagonist (A2 value, 1.7 X 10(-6) M). The selectivity for the beta 1-adrenergic receptor was higher for N than for any of the reference compounds. In dogs--similarly with atenolol--N was more potent in blocking the isoprenaline (I)-induced increases in left ventricular performance than the I-induced decrease in arterial pressure. In dogs, as compared with propranolol, N (0.025 and 0.01 mg.kg-1 i.v.) increased cardiac output and stroke volume, lowered systemic vascular resistance, and had no significant effect on the variables related to left ventricular contraction. In contrast to other beta-adrenergic antagonists, N acutely lowered arterial blood pressure in SHR (1.25 mg.kg-1 i.p.) and in hypertensive patients (1 oral dose of 5 mg) for several hours. In healthy volunteers N (5 mg) lowered systemic vascular resistance during daily oral treatment and did not negatively affect left ventricular function. In conclusion, N is a potent and selective beta 1-adrenergic blocking agent with an interesting hemodynamic profile. In hypertensive subjects and SHR, a single dose lowers arterial blood pressure for substantial periods of time.

Adrenergic alpha-Antagonists↗
PubMed1988

Absorption, metabolism and excretion of ketanserin in man after oral administration.

The absorption, metabolism and excretion of ketanserin [+)-3-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2,4(1H,3H)- quinazolinedione, R 41 468), a novel serotonin S2-receptor antagonist used in hypertension, was studied after a single oral dose of 14C-ketanserin tartrate in three healthy subjects. Absorption from the gastrointestinal tract was rapid and almost complete. The excretion of radioactivity amounted to about 90% after 4 days and was more abundant in urine (68%) than in faeces (24%). Ketone reduction and oxidative N-dealkylation at the piperidine nitrogen were by far the two main metabolic pathways. The former pathway resulted in ketanserin-ol, the main metabolite in plasma as well as in urine (24% of dose) and faeces (5%), the latter pathway in the urinary metabolite 1,4-dihydro-2,4-dioxo-3(2H)quinazolineacetic acid (20%). Other pathways were aromatic hydroxylation at the quinazolinedione moiety and the formation of ether glucuronides. None of the metabolites substantially contributes to the overall pharmacological activity of ketanserin. The metabolic pathways of ketanserin in man were identical to those revealed previously in rats and dogs, but the mass balance of the major metabolites resembled more that in dogs than that in rats.

Administration, Oral↗
PubMed1987

ECG studies with astemizole.

1 Six healthy volunteers took part in a 2-week haemodynamic safety study of astemizole. 2 They were given 30 mg daily (3 X 10 mg tablets) for the first 3 days and 10 mg daily for the next 12 consecutive days. 3 Heart rate, blood pressure, ECG and systolic time intervals at rest were measured before the start and five times during the day. 4 No changes were observed in any of the parameters measured. The configuration of the ECG was not influenced. 5 Serum concentrations of astemizole plus hydroxylated metabolites measured at the end of the study were 16 times lower than those detected in a patient overdosing on 200 mg astemizole.

Adult↗
PubMed1985

The effect of ketanserin, a 5-HT2-receptor antagonist, on 5-hydroxytryptamine-induced irreversible platelet aggregation in patients with cardiovascular diseases.

Platelet aggregation in response to 5-hydroxytryptamine was investigated in 40 normal subjects, in 45 patients with acute myocardial infarction, and in 65 patients with peripheral arterial obstructive disease. It was found that of the 110 patients with cardiovascular disease, 40% had a biphasic irreversible platelet aggregation, whereas this phenomenon occurred in only 7.5% of the normal population. A double-blind placebo-controlled study further showed that a subacute treatment with ketanserin, a selective 5-HT2-receptor antagonist both on platelets and on vascular tissue, efficiently abolished the irreversible platelet aggregation in patients hyperreactive to 5-hydroxytryptamine. In an additional open study, including 10 patients with peripheral arterial obstructive disease, a chronic treatment with ketanserin 40 mg t.i.d. for a period of 3 months significantly suppressed the primary platelet aggregation to 5-HT at 2 X 10(-5) M and at 2 X 10(-6) M and significantly lowered the plasma beta thromboglobulin levels. Since 5-HT is a potent mediator of vasospasm, treatment with ketanserin might be of therapeutic value in atherosclerotic diseases, where platelet activation is thought to be involved.

Aged↗
PubMed1985

Effect of ketanserin on the hyperreactivity of platelets to 5-hydroxytryptamine in patients with cardiovascular diseases.

Platelet aggregation in response to 5-hydroxytryptamine (5-HT) was investigated in 110 patients with cardiovascular diseases and in 40 age-matched control subjects. It was found that 40% of those patients had a biphasic irreversible platelet aggregation in response to 5-HT, whereas 92.5% of the control subjects responded with a weak reversible aggregation. A double-blind, placebo-controlled study, including 41 patients, showed that a subacute treatment with ketanserin significantly abolished platelet aggregation in patients hyperreactive to 5-HT. In an additional open study, including 10 patients with peripheral arterial obstructive disease, chronic treatment with ketanserin for a period of 3 months significantly suppressed the primary platelet aggregation to 5-HT at 2 X 10(-5) M and at 2 X 10(-6) M and significantly lowered the plasma beta-thromboglobulin levels.

Adult↗
PubMed1985

Ketanserin and red blood cell sodium content in hypertension.

The sodium content of erythrocytes from patients with essential hypertension is increased. In a double-blind, placebo-controlled study, a 5-day treatment with ketanserin, a serotonergic antagonist lowered significantly the sodium content of the red blood cells (RBC). Ouabain induces an increase of sodium content of the RBC, which is paralleled by a decrease in RBC deformability. The ouabain-dependent fraction of RBC deformability is significantly reduced after a single oral dose of ketanserin. In vitro, serotonin (5-HT) decreases RBC deformability; this effect could be antagonized by ketanserin. These data might suggest a regulating role of 5-HT in transmembrane ion fluxes.

Adult↗
PubMed1985

Comparison of blood pressure ratio by Doppler velocimetry and by plethysmography during treatment with ketanserin, a 5-HT2 receptor antagonist: a measure of improved collateral and microcirculatory flow.

We could demonstrate a progressive and significant increase in blood pressure ratio (thigh/arm) in 42 patients with intermittent claudication, treated with ketanserin for 9 months, which confirms our earlier double-blind placebo-controlled findings. In an additional experiment comparing blood pressure ratio with Doppler velocimetry and with plethysmography, an upwards shift was observed for the plethysmographic values as compared with the Doppler values during ketanserin therapy, and only at the level of the thigh, which suggests an improvement of the collateral and microcirculatory flow.

Aged↗
PubMed1984

Placebo-controlled double-blind trial of ketanserin in treatment of intermittent claudication.

Ketanserin, a selective serotonin (5-HT) antagonist at 5-HT2 receptors, was investigated in a 3-month, double-blind, placebo-controlled study in twenty patients with intermittent claudication. Blood-pressure ratio (thigh/arm), reactive hyperaemia measured with an ECG-triggered venous occlusion plethysmograph, blood filterability, and claudication distance on a treadmill progressively and significantly improved during ketanserin therapy, whereas no such changes occurred in the placebo group. Mean claudication distance improved by 140%; four of the eleven patients on ketanserin were able to keep walking beyond the time limit of the exercise test. The beneficial effect of ketanserin suggests that 5-HT may be involved in the pathogenesis of peripheral arterial obstructive diseases. In an experiment comparing blood-pressure ratio measured by doppler velocimetry and by plethysmography, the plethysmographic values rose during ketanserin therapy only at thigh level, which suggests an improvement in the collateral circulation.

Aged↗
PubMed1982

Enumeration of T-lymphocytes and T-lymphocyte subsets in rheumatoid arthritis using monoclonal antibodies.

The number of T-lymphocytes and T-lymphocyte subsets was measured in peripheral blood of 51 patients with rheumatoid arthritis. T-lymphocytes were counted by E-rosette tests and by the immunogold staining method with OKT3.PAN monoclonal antibody. Helper and suppressor T-lymphocytes were determined by the immunogold staining method with OKT4.IND and OKT8.SUP monoclonal antibody. The relative and absolute numbers of T-lymphocytes and helper T-lymphocytes in peripheral blood of patients with RA did not differ significantly from those in the blood of healthy subjects. However, the relative and absolute numbers of suppressor T-cells were significantly lower in patients with RA than in healthy subjects. The decrease of suppressor T-cells in the blood of patients with RA dit not correlate with the activity of the disease nor the presence of the rheumatoid factor.

Adult↗
PubMed1981

The antihypertensive effects of a pure and selective serotonin-receptor blocking agent (R 41 468) in elderly patients.

In a first experiment, an acute intravenous administration of 10 mg R 41 468, a pure serotonin-receptor blocking agent with high selectivity for blood vessels and thrombocytes and devoid of central effects, dramatically reduced systolic and diastolic blood pressure in 23 elderly hypertensive patients. Heart rate and cardiac output remained virtually unchanged. In a second double-blind placebo-controlled cross-over study a highly significant decrease of systolic and diastolic blood pressure was obtained in 14 elderly hypertensive patients during an 8-day oral treatment with 40 mg t.i.d. of R 41 468. No serious side-effects were observed. An oral maintenance therapy with R 41 468 for 3 weeks showed a further reduction of blood pressure, resulting in a normalization of blood pressure, taking into account the advanced age of the patients. R 41 468 most probably acts by decreasing the venous capacitance bed constriction. Essential hypertension might be causally related to an impairment of venous function, in which serotonin might be an important pressor factor.

Age Factors↗
PubMed1981

Enumeration of T lymphocytes subsets in autoimmune disease using monoclonal antibodies.

The numbers of T lymphocytes, B lymphocytes, helper and suppressor T lymphocytes were measured in peripheral blood of patients with autoimmune disease (rheumatoid arthritis, erythema nodosum, Sjögren's disease, Wegener's disease, idiopathic thrombocytopenia, pernicious anaemia and Hashimoto's disease). B lymphocytes were enumerated by direct immunofluorescence and T lymphocytes by E rosette tests and by indirect immunofluorescence with OKT3.PAN Helper and suppressor T lymphocytes were determined by indirect immunofluorescence with OKT4.IND and OKT8.SUP respectively. The numbers of T lymphocytes, B lymphocytes and helper T lymphocytes in patients with autoimmune disease were normal, but the numbers of suppressor T lymphocytes were significantly lower.

Adolescent↗
PubMed1980

Measurement of mitogen stimulation of lymphocytes with a glucose consumption test.

The increase of glycolysis in mitogen-stimulated lymphocytes was used to quantify lymphoblast transformation. Results correlated well with those by common methods, i.e. morphological evaluation and [3H]thymidine incorporation. The advantage of the glucose consumption test is that it registers the entire event of lymphocyte proliferation whereas other methods evaluate only viable transformed cells at the end of culture.

Concanavalin A↗
PubMed1980

Oxatomide in the treatment of various allergic diseases.

The use of oral oxatomide (30 to 360 mg per day) for the treatment of allergic conditions of the bronchi, skin and gastro-intestinal tract was investigated in a total of 70 subjects. Therapeutic results were evaluated at intervals ranging between 1 and 16 months. Symptomatic improvements were scored globally, forced expiratory volume in 1 second was measured in asthmatic patients, and the lesions of atopic dermatitis were rated according to a modified Clendening scale. The results suggest that oxatomide was particularly effective in the treatment of allergic rhinitis and skin allergies. Allergic asthma responded fairly well in patients with a short history of disease and gastro-intestinal conditions reacted moderately, with haemorrhagic rectitis responding better than gastritis. These findings warrant further controlled trials of oxatomide in such conditions.

Adolescent↗