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Biomedical subjects

P Dupont

Publications and source records attributed to P Dupont.

At least 109 records · Page 6Linked to original sources

Metabolism of arachidonic acid through the 5-lipoxygenase pathway in normal human peritoneal macrophages.

Peritoneal macrophages (PM), obtained from 39 healthy women with normal laparoscopy findings, were stimulated with the ionophore A23187 or/and arachidonic acid (AA) both in adherence and in suspension. AA lipoxygenase metabolites were determined by reversed-phase HPLC. The major metabolites identified were 5-hydroxyeicosatetraenoic acid (5-HETE), leukotriene (LT)B4 and LTC4. The 20-hydroxy-LTB4, 20-carboxy-LTB4, and 15-HETE were not detected. Incubations of adherent PM with 2 microM A23187 induced the formation of LTB4, 110 +/- 19 pmol/10(6) cells, 5-HETE, 264 +/- 53 pmol/10(6) cells and LTC4, 192 +/- 37 pmol/10(6) cells. When incubated with 30 microM exogenous AA, adherent PM released similar amounts of 5-HETE (217 +/- 67 pmol/10(6) cells), but sevenfold less LTC4 (27 +/- 12 pmol/10(6) cells) (p less than 0.01). In these conditions LTB4 was not detectable. These results indicate that efficient LT synthesis in PM requires activation of the 5-lipoxygenase/LTA4 synthase, as demonstrated previously for blood phagocytes. When stimulated with ionophore, suspensions of Ficoll-Paque-purified PM produced the same lipoxygenase metabolites. The kinetics of accumulation of the 5-lipoxygenase/LTA4 synthase products in A23187-stimulated adherent cells varied for the various metabolites. LTB4 reached a plateau by 5 min, whereas LTC4 levels increased up to 60 min, the longest incubation time studied. Levels of 5-HETE were maximal at 5 min, and then slowly decreased with time. Thus, normal PM, in suspension or adherence, have the capacity to produce significant amounts of 5-HETE, LTB4, and LTC4. The profile of lipoxygenase products formed by the PM and the reactivity of this cell to AA and ionophore A23187 are similar to those of the human blood monocyte, but different from those of the human alveolar macrophage.

Adult↗

Comparison of the central and peripheral effects of cetirizine and terfenadine.

The peripheral and central effects of 10 mg cetirizine 2 HCl and 60 mg terfenadine have been compared with placebo in 9 healthy male volunteers. The peripheral effect, in terms of cutaneous reactivity to 1 microgram histamine i.d., was measured by planimetry of the wheal and erythemas. Central effects were assessed with a self-evaluation visual scale and from the results of electroencephalographic spectrum analysis. Peripheral inhibition of histamine reactivity was more intense and quicker for cetirizine than for terfenadine. On the self-evaluation scale, no significant difference between terfenadine, cetirizine and placebo was noted. The quantified EEG did not show any variation in spectral parameters at any time after cetirizine. By contrast, at 6 h terfenadine had increased slow waves and had inhibited the alpha band. Thus, 10 mg cetirizine 2 HCl had less effect on the central nervous system than terfenadine 60 mg, whilst its peripheral action appeared more quickly and was more intense.

Adult↗

Lack of potentiation by cetirizine of alcohol-induced psychomotor disturbances.

The possible interaction between cetirizine 2 HCl and alcohol was studied in a double-blind, cross-over trial in 36 healthy volunteers. The performance of each volunteer was tested with a battery of five objective psychometric tests, and their subjective feelings were evaluated by visual analogue scales, and by extensive questionnaire. The psychomotor performance and subjective inventory of health was significantly impaired by alcohol intake. Cetirizine 2 HCl was not different from placebo. There was no adverse interaction between cetirizine 2 HCl and alcohol. Cetirizine and alcohol did not modify each others blood levels.

Adult↗

Ketanserin combined with a beta-blocker or diuretic in essential hypertension. A multicentre study.

The antihypertensive effect of ketanserin 40 mg b.d. in combination with a beta-adrenergic blocking agent or a diuretic was assessed in an open study in 35 patients with essential hypertension, who had not responded to treatment with beta-blockers, diuretics or their combination. The ketanserin/beta-blocker combination decreased mean sitting systolic/diastolic blood pressure (SBP/DBP) from 169/107 mmHg to 156/91 mmHg at the end of the 12-week active treatment period. The decrease in systolic blood pressure was significant only at Week 8, while the decrease in diastolic blood pressure was highly significant at all times. A significant reduction in heart rate by 10 beats.min-1 was observed with the ketanserin + beta-blocker combination. The ketanserin/diuretic combination led to a significant reduction in mean SBP/DBP from 164/106 mmHg to 146/92 mmHg after 12 weeks, with no significant change in heart rate. Body weight slightly increased in both groups. There were significantly fewer adverse reactions with the ketanserin/diuretic combination than with the ketanserin/beta-blocker combination. The results indicate a potentially useful therapeutic role for ketanserin in combination with beta-blockers or diuretics.

Adrenergic beta-Antagonists↗

Comparative study of the peripheral and central effects of terfenadine and cetirizine 2 HCl.

The histamine cutaneous reactivity of healthy volunteers was measured after a single oral intake of placebo, terfenadine 60 mg and 180 mg, and cetirizine 2 HCl 10 mg. Central side effects were evaluated by Visual Analog Scales for drowsiness and movement coordination. The anti-H1 cutaneous effect of cetirizine 2 HCl proved to be significantly more rapid, more pronounced, and longer lasting than that of terfenadine 60 mg. Cetirizine and terfenadine 180 mg were equipotent. The Visual Analog Scales for central nervous system effects did not show any difference between cetirizine, terfenadine, and placebo.

Adult↗

Long-term study of the safety of the Dalkon Shield and Gyne-T 200 intrauterine devices.

Between 1971 and 1973, 200 Dalkon Shield and 142 Gyne-T 200 intrauterine devices (IUDs) were inserted at the department of obstetrics and gynecology in a large urban hospital. In 1984 retrospective analysis of events associated with the use of these IUDs was done. Hospital and clinic charts were reviewed, and the women were contacted to obtain information on infertility and the outcome of pregnancy after discontinuation of IUD use. The rates of events leading to discontinuation of IUD use 2 years after insertion were similar in the two groups except for that of planned pregnancy, which was higher in the Dalkon Shield users (p less than 0.05). The rates of accidental pregnancy per 100 women were 3.8 for the Dalkon Shield users and 1 for the Gyne-T 200 users. The rates of pelvic inflammatory disease (PID) based on all cases of PID and follow-up information were similar in the two groups. There were no differences between the two groups in outcome of pregnancy with the IUD in situ or after expulsion or removal of the IUD because of planned pregnancy or other reasons. Infertility rates after discontinuation of IUD use were similar for the Dalkon Shield and Gyne-T 200 users. The results confirm the authors' opinion that the Dalkon Shield and Gyne-T 200 IUDs are safe and effective methods of intrauterine contraception.

Adult↗

Pregnancy after IUD use.

Much has been written about the risks of PID to IUD users, but very little about the subsequent fertility status of these patients. Is tubal infertility increased in an IUD user who has been asymptomatic? Does the addition of copper make the device harmless? Was the Dalkon Shield so harmful in the nulliparous woman? Our study (89 and 90% follow-up after 12-14 years) of 200 Dalkon Shield and 142 TCu-200 users allows us to answer 'No' to the three previous questions. We conclude that wearing an IUD per se does not cause infertility since all our patients who had IUDs removed for intended pregnancy did become pregnant; the addition of copper per se does not make an IUD safer although it does make it more efficient; the Dalkon Shield used in nulligravidas was not more dangerous than other types of IUD.

Female↗

Intermittent claudication: a double-blind crossover trial of pentoxifylline.

The influence of the xanthine derivative pentoxifylline ('Trental' or BL191; Hoechst-Roussel) on exercise tolerance was measured in 38 subjects with stable, severe to moderately severe, intermittent claudication who completed a randomised, double-blind, placebo controlled, cross-over clinical trial. Patients received placebo tablets or 400 mg slow-release pentoxifylline tablets ('Trental 400') twice a day for one week, followed by three times daily for seven weeks, and then crossed over to receive the alternate preparation for another eight weeks. Claudication distance and walking distance were measured on a treadmill before starting treatment and again at four-week intervals during the trial. At the same times, red blood cell filterability, plasma fibrinogen concentration and blood viscosity, resting and post-ischemic calf muscle blood flow, and the resting and post-exercise ankle/brachial systolic pressure ratio were also measured. In this study, the observed effects of pentoxifylline treatment were no greater than those of placebo, even though serum levels of pentoxifylline and its hydroxy-metabolite were within the anticipated range. This was shown by a 'therapeutic effect ratio' of 0.98 for treadmill claudication distance and 0.96 for treadmill walking distance after within-patient analysis at the end of the cross-over (where a ratio of 1.0 means the test drug and placebo effects are identical). These ratios have 95% confidence limits of 0.72-1.34 and 0.74-1.25, respectively.

Aged↗

Effect of cimetidine on serum carboxyl and aminoterminal fragments of parathyroid hormone in chronic uraemic patients.

The effect of cimetidine on abnormally elevated serum levels of parathyroid hormone was studied in 21 patients with secondary hyperparathyroidism due to chronic renal failure, receiving regular dialysis treatment. The concentrations of carboxyl (-COOH) and aminoterminal (-NH2) fragments of circulating immunoreactive parathyroid hormone (iPTH) were determined before and after 2 months af treatment with cimetidine 400 mg/day. All patients had, on admission, raised levels of either hormonal fragment. The mean pre-treatment value was 17.2 mU/ml for -COOH terminus (upper normal limit 6.5 mU/ml) and 5.7 mU/ml for -NH2 terminus (upper normal limit 1.9 mU/ml). At the end of cimetidine treatment the mean values were 19.9 and 5.7 mU/ml respectively for the two forms of circulating iPTH. No changes in total serum calcium, phosphate or alkaline phosphatase activity were recorded during the study. These results do not indicate any lowering effect of cimetidine on serum iPTH in chronic uraemic patients with secondary hyperparathyroidism.

Adult↗