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P Nony

Publications and source records attributed to P Nony.

At least 37 records · Page 2Linked to original sources
PubMed1996

Platelet-aggregation inhibition and hemodynamic effects of beraprost sodium, a new oral prostacyclin derivative: a study in healthy male subjects.

The antiaggregation and hemodynamic effects of the new prostacyclin analogue beraprost sodium were investigated in a randomized, placebo-controlled, double-blind clinical trial of Latin-square design. Twelve healthy Caucasian males randomly received 8-day oral treatments of 20, 40, and 60 micrograms of beraprost sodium and a placebo. One-week washout periods followed each treatment. Pharmacokinetic and pharmacodynamic measurements were performed on days 1 and 8 for each period of treatment. All three doses of beraprost sodium significantly inhibited platelet aggregation on day 8 (compared with placebo) during the 1st h after drug intake. Incubation of the 60-micrograms beraprost sodium samples with ADP (2, 5, and 10 microM) and collagen (1.25 micrograms/mL) decreased platelet aggregation by 10, 19, 16, and 6 +/- 4% (mean +/- SE), respectively, compared with placebo. No significant hemodynamic effects on blood pressure, heart rate, and digital pulse were observed. The 60-micrograms dose of beraprost sodium did significantly decrease the IRZ index (which may reflect the left ventricular pre-ejection period) on days 1 and 8. Some subjects experienced headache and facial flushing, effects that were dose dependent and reversible. Beraprost sodium at 20- to 60-micrograms doses exerts platelet antiaggregation (day 8 of therapy) and slight hemodynamic (days 1 and 8 of treatment) effects in Caucasian males. Beraprost sodium hemodynamic effects and potential benefits in patients with cardiovascular disease should be explored further.

Administration, Oral↗
PubMed1996

Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis.

Osteoporosis is the main cause of spine and hip fractures. Morbidity, mortality, and costs arising from hip fractures have been well documented. Thyroid hormones (TH) are widely prescribed, mainly in the elderly. Some studies (but not all) found a deleterious effect of suppressive TH therapy on bone mass. These conflicting data raised a controversy as to the safety of current prescribing and follow-up habits, which, in turn, raised major health-care issues. To look for a detrimental effect on bone of TH therapy, we performed a meta-analysis (by pooling standardized differences, using a fixed effect model) of all published controlled cross-sectional studies (41, including about 1250 patients) concerning the impact of TH therapy on bone mineral density (BMD). Studies with women receiving estrogen therapy were excluded a priori, as were studies with a high percentage of patients with postoperative hypoparathyroidism, when no separate data were available. We decided to stratify the data according to anatomical site, menopausal status, and suppressive or replacement TH therapy, resulting in 25 meta-analysis on 138 homogeneous subsets of data. The main sources of heterogensity between studies that we could identify were replacement or suppressive TH therapy, menopausal status, site (lumbar spine, femoral neck, Ward's triangle, greater trochanter, midshaft and distal radius, with various percentages of cortical bone), and history of hyperthyroidism, which has recently been found to impair bone mass in a large epidemiological survey. To improve homogeneity, we excluded a posteriori 102 patients from 3 studies, who had a past history of hyperthyroidism and separate BMD data, thus allowing assessment of the TH effect in almost all 25 subset meta-analyses. However, controls were usually not matched with cases for many factors influencing bone mass, such as body weight, age at menarche and at menopause, calcium dietary intake, smoking habits, alcohol intake, exercise, etc. For lumbar spine and hip (as for all other sites), suppressive TH therapy was associated with significant bone loss in postmenopausal women (but not in premenopausal women), whereas, conversely, replacement therapy was associated with bone loss in premenopausal women (spine and hip), but not in postmenopausal women. The detrimental effect of TH appeared more marked on cortical bone than on trabecular bone. Only a large long term prospective placebo-controlled trial of TH therapy (e.g. in benign nodules) evaluating BMD (and ideally fracture rate) would provide further insight into these issues.

Adult↗
PubMed1996

[Diagnostic value of echocardiography under dobutamine in everyday practice].

In order to evaluate the place of dobutamine echocardiography in everyday practice, this test and a stress ECG were performed in 34 patients referred for diagnostic or assessment coronary angiography. Dobutamine, administered in 3-minute stages from 5 to 30 micrograms/kg/min, was well tolerated. The anti-ischaemic treatment was continued in 26 patients before dobutamine echocardiography and in 15 patients before the stress ECG. The electrocardiographic, echocardiographic and angiographic documents were each analysed by 2 independent observers. Dobutamine echocardiography was considered to be positive in the presence of the development of a new abnormality of segmental kinetics or when abnormality of segmental kinetics was identified outside of the territory of infarction. With reference to coronary angiography, the sensitivity of stress ECG and dobutamine echocardiography was 46% and 42%, respectively, and the specificity was 75% and 88%, respectively; the sensitivity of each test was low, probably because of fake tests. The combination of the two tests improved the sensitivity (69%) without altering the specificity (75%). Dobutamine echocardiography could usefully complete a negative stress ICG whenever a false-negative result is suspected to avoir wrongly reassuring some patients and to allow appropriate management.

Adult↗
PubMed1995

Dose-ranging trials: guidelines for data collection and standardized descriptions.

Protocols for dose ranging trials in healthy volunteers or patients can be described by the combination of an experimental design and one or more decision rules. Generally, the doses are chosen on the basis of an up-and-down method, until the maximum tolerated (affecting one or more physiological parameters) and the minimum effective doses are found. Despite the large number of possible protocols there is no standard for the description of the experimental design or the decision rule(s). We propose a series of variables that can be used to facilitate data collection and that can adequately and uniquely characterize most dose ranging protocols.

Clinical Protocols↗
PubMed1995

Regulation of the P25 gene transcription in the silk gland of Bombyx.

The gene encoding the silk protein P25 is specifically transcribed in the posterior silkgland of Bombyx during larval intermoults and is repressed during moults. By performing in vitro DNA-protein interactions, at least five putative regulatory elements were localized in the 5' flanking region of the gene. The most proximal element, close to the TATA box, interacts with SGFB, a silkgland-specific factor which could be involved in the tissue-specific expression of the gene. A more upstream sequence is recognized by an ubiquitous factor, BMFA, which exhibits cyclical modifications in relation to the moulting cycle and could thus be involved in the temporal control of the gene during the development. A construct containing a reporter gene fused to 1450 bp of P25 5' flanking sequences was integrated into the Drosophila genome and shown to be specifically expressed in the larval salivary gland, the organ homologous to the silkgland. Recurrent deletions of this construct showed that the proximal 254 bp contain all the sequences required for this specific expression. Similar foreign constructs introduced in the silkgland in vivo by a particle delivery system were specifically transcribed in the posterior silkgland but remained silent in the middle silkgland as the endogenous genes. This methodology will be used to assay the function of the defined cis-acting elements in the spatial regulation of expression of P25.

Animals↗
PubMed1995

[Introduction to meta-analytic methodology].

General considerations about meta-analysis and the different steps of this technique are successively discussed: definition of the main objective, identification of the outcome, description of the retrieval and selection of trials, description of the statistical analysis and interpretation of the results. Advantages and drawbacks of the meta-analytical technique are then described: 1) scientific approach, possible quantification of the therapeutic effect, increase of the power of a future clinical trial, synthesis of contradicting results, assessment of the homogeneity, subgroup analysis, analysis of sensibility, scientific collaboration, help for therapeutic information. 2) retrospective approach, inconsistency among trials, potential biases, persistence of some unsolved methodological problems, difficulties for a critical reading and for the interpretation of conclusions. In addition, some examples of published meta-analyses are given to illustrate the advantages and limits mentioned above.

Humans↗
PubMed1994

Evaluation of the effect of phosphodiesterase inhibitors on mortality in chronic heart failure patients. A meta-analysis.

We examined the influence of phosphodiesterase inhibitors (PDIs) on mortality in patients with overt chronic heart failure. A total of 13 randomised, placebo-controlled trials of PDIs involving 2808 patients were selected. Meta-analysis, using data for all patients, showed that there was a non-significant (P = 0.16) increase of about 17% in the mortality rate of patients receiving a PDI [odds ratio (OR) 1.17, 95% confidence interval (CI) 0.94-1.46]. However, the observed treatment effects were found to be heterogeneous due to the results from the trials on vesnarinone. The heterogeneity became non-significant (P = 0.77) when these trials were removed, and a significant increase in the mortality rate was observed under treatment with the other PDIs (OR 1.41, 95% CI 1.11-1.79). In the subgroups of patients with or without additional vasodilator (VD) treatment, similar results were observed (PDI with VD: OR 1.3, 95% CI 1.03-1.7; PDI without VD: OR 2.04, 95% CI 1.1-3.8). These results indicate that PDIs (with the exception of vesnarinone) should not be prescribed for long-term use in patients with overt chronic heart failure. Additional vasodilator treatment in patients receiving PDIs for chronic heart failure does not explain the increased mortality seen with PDIs. This toxicity must, therefore, arise by other mechanisms. Further experimental and clinical evaluation is needed to confirm the beneficial influence of vesnarinone on survival in chronic heart failure patients and to identify the mechanism(s) differentiating this agent's therapeutic effect from that of other PDIs.

Adult↗
PubMed1994

Structural features of mag, a gypsy-like retrotransposon of Bombyx mori, with unusual short terminal repeats.

Mag is a retrotransposon found as an insert in the Sericin 2 gene. It is present in a few copies--4 to 15--dispersed in the genome of different strains of Bombyx mori as well as in Bombyx mandarina. Flanked by a 5 bp target sequence with no sequence specificity, it is bordered by direct repeats of 77 nucleotides. Despite their unusual short size, these terminal repeats and their immediately adjacent sequences present all the signals necessary for transcription into genomic RNA and for reverse transcription. Mag contains two overlapping open reading frames which are organized as the gag and pol genes of retroviruses and encode putative nucleic acid binding peptide, protease, reverse transcriptase, RNase H and endonuclease in this order. Sequence comparison of these proteins places mag within the gypsy group of LTR retrotransposons next to the echinoderm element SURL.

Amino Acid Sequence↗
PubMed1994

The role of an initial single-blind placebo period in phase I clinical trials.

The effect of an initial single-blind placebo period in a phase I clinical trial was assessed in 12 volunteers who underwent five weekly treatment periods, consisting of treatment on the first day and a six-day wash-out period. An initial single-blind placebo period was followed by three different single doses of a platelet-aggregation factor inhibitor and another placebo period, under a double-blind Latin square design. Reports of abnormal symptoms were collected using a questionnaire designed by our group. A total of 13 abnormal symptoms were reported during the first period and only nine for the following four periods, indicating a clear placebo period effect. These preliminary results suggest that an initial single-blind period may be usefully included in phase I clinical trials.

Clinical Trials, Phase I as Topic↗
PubMed1993

Electrophysiologic effects of a potassium channel activator (pinacidil) on repolarization parameters in healthy volunteers: a surface ECG study.

About a quarter to a third of patients receiving pinacidil, a new cyanoguanidine vasodilator, show ECG changes, in particular T-wave modifications that sometimes mimic myocardial ischemia. To investigate these changes, we performed a randomized placebo-controlled trial in 10 carefully selected, healthy subjects who received single oral doses of either pinacidil (25 mg), quinidine (330 mg), and placebo. Quinidine, which induces specific modifications to the surface ECG signal, was used as an internal control. The complete experimental design involved five consecutive administrations of the drugs in random order: pinacidil (twice), quinidine (twice), and placebo (once), separated by a week-long washout period. Electrophysiologic data acquisition and signal analysis were performed with the Lyon vectocardiographic processing system. Pinacidil decreased T-wave amplitude (-0.26 +/- 0.1 mV) significantly as compared with placebo (-0.14 +/- 0.06 mV), but did not change the duration of the T-wave. Although the cardiac rate increased with pinacidil, the QTc interval remained constant. Conversely, quinidine did not modify the RR interval but significantly increased duration of the T-wave (+67 +/- 20 ms) and QTc interval (+53 +/- 13 ms) as compared with placebo (+17 +/- 13 and +18 +/- 11 ms). In addition, no specific ischemic changes to the T-loop were observed with pinacidil. The modifications to the surface ECG signal caused by pinacidil appear to be drug-specific and related to its electrophysiologic properties rather than involving any ischemic mechanism. Such an approach may be useful for describing morphologic ECG changes caused by new drugs and identifying possible underlying electrophysiologic mechanism(s), which should then be confirmed in further studies.

Administration, Oral↗
PubMed1992

Anomalous origin of left coronary artery from the pulmonary artery: evolution of left ventricular function and perfusion after surgery in a 44-year-old man.

Anomalous origin of left coronary vessel from the pulmonary artery is an almost universally fatal form of congenital heart disease unless appropriate corrective surgery is performed at an early age. A case was diagnosed in a symptomatic 44-year-old man who presented an impairment of systolic left ventricular function. The abnormality was successfully treated with ligation of the left coronary artery combined with left internal mammary artery anastomosis. Left ventricular function improved dramatically six months after surgery, both at rest and during exercise. Such an evolution suggests that surgery may be indicated not only in infants but also in adults with this congenital heart abnormality.

Adult↗
PubMed1992

Relative efficacy of angiotensin converting enzyme inhibitors on mortality of patients with congestive heart failure: implications of randomized trials and role of the aetiology (ischaemic or non-ischaemic) of heart failure.

We examined the influence of angiotensin converting enzyme inhibitors (ACE inhibitors) on mortality in patients with heart failure of both ischaemic or non-ischaemic origin. Eleven, randomized, placebo-controlled trials of ACE inhibitors involving 1266 patients were selected. The follow-up period varied from 3 to 6 months. Four different ACE inhibitors were used in the 11 clinical trials. A total of 679 patients presented with an ischaemic heart failure and 587 with a non-ischaemic heart failure. Meta-analysis, performed for both subgroups, showed that mortality was significantly decreased in the ischaemic subgroup only (ischaemic group: odds ratio 0.45; 95% confidence interval 0.28 to 0.71; non-ischaemic subgroup: odds ratio 0.7; 95% confidence interval 0.4 to 1.5). Although the two odds ratio are not significantly different, further randomized, placebo-controlled trials with ACE inhibitors are required in order to determine more precisely the benefit/risk ratio in patients with non-ischaemic heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

[Abnormal origin of the left coronary artery in the adult. Scintigraphic and surgical correlations].

The authors report two cases of anomalous origin of the left coronary artery from the pulmonary artery in the adult. The two patients were pauci-symptomatic and were successfully operated, the one by reimplantation of the left coronary artery in the aorta and the other by an internal mammary artery left anterior descending artery bypass. Resting and stress myocardial scintigraphy and radionuclide ventriculography were performed before and after surgery in both cases. An analysis of segmental wall motion was possible in one patient. Before surgery, there was hypo-fixation of the tracer during the stress test and an alteration of left ventricular function. Postoperative isotopic investigations confirmed the efficacy of surgery the absence of regional ischemia and the normalisation of the ventricular contraction. These results argue in favour of a surgical reconstruction of a two coronary system, given the spontaneous risk of sudden death in this condition.

Adolescent↗
PubMed1990

The place of simultaneous pharmacokinetic pharmacodynamic modeling in new drug development: trends and perspectives.

The potential applications in drug development of pharmacokinetic-pharmacodynamic modeling are numerous: optimal medication regimen, design of galenic forms, identification of specific effects of metabolites and enantiomers. Nevertheless, this methodology is presently under-used, as appears from an analysis of the literature. We examine this point as well as progress in both non-invasive pharmacodynamic measurement and specific experimental design that could lead to a future extension of PK-PD in toxicology and phase I drug development.

Drug Evaluation↗
PubMed1990

Private hospital and phase I.

Since December 1988. French law has authorized phase I studies and the creation of phase I units within public or private hospitals. The scientific standards regarding private hospitals are not different from those in public hospitals. Practitioners who conduct clinical trials in private hospitals are well aware of good clinical practices and methodological constraints. Phase I units can be structured in private as well as within public hospitals. Finally, the question to be addressed is whether clinical pharmacology and scientific investigations in healthy volunteers should be integrated in the policy of private hospitals.

Drug Evaluation↗
PubMed1989

[Prognosis of chronic non-dystrophic and surgically treated aortic insufficiency].

Between January 1972 and March 1983, 123 patients with isolated non dystrophic aortic insufficiency underwent aortic valve replacement. During a mean follow-up period of 4.3 years per patient, 25.6 p. 100 of the patients died, including a 4.1 p. 100 hospital death rate. The actuarial survival rate was 74 p. 100 at 5 years and 62 p. 100 at 10 years. The main causes of mortality were heart failure, dysrhythmias and sudden death. A study of prognostic factors based on the preoperative data showed that clinical, radiological, electrocardiographic and haemodynamic signs were informative. In agreement with other authors, we found that preoperative cardiac dilatation and left ventricular dysfunction were predictive of a poor prognosis.

Adult↗
PubMed1988

Doxorubicin concentrations in plasma and myocardium and their respective roles in cardiotoxicity.

Three hours after the intravenous infusion of doxorubicin (3 mg/kg over 15 min) to anesthetized dogs, the drug concentration was found much higher in the myocardium than in the plasma (about 4,000 ng/g, i.e., 50 times higher). After the intravenous infusion of doxorubicin (1.5 mg/kg over 15 min) to conscious dogs, the drug concentration appeared to decline very slowly in the myocardium, since it was close to 200 ng/g at the 7th day, whereas the plasma concentration had fallen to zero, and the drug was still detected in the cardiac tissue 21 days after the administration. As myocardial concentrations of doxorubicin persist long after plasma clearance is complete, the hazards of repeated administration, based on plasma kinetic patterns, must be emphasized.

Animals↗