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Biomedical subjects

O Piot

Publications and source records attributed to O Piot.

At least 37 records · Page 2Linked to original sources
PubMed1998

[A randomized double-blind trial comparing cibenzoline and disopyramide in the prevention of recurrences of atrial tachyarrhythmia].

The aim of this multicenter, randomised, double-blind trial was to compare the efficacy and tolerance of oral disopyramide (D: 250 mg slow release twice daily) compared with cibenzoline (C: 130 mg twice daily) in the prevention of recurrences of atrial arrhythmias over a 6 month period. Sixty patients (mean age: 62 +/- 14 years; 37 men, 23 women; cardiac disease in 60% of cases) were randomised to two groups: C (N = 31) and D (N = 29). The commonest arrhythmia was atrial fibrillation (83%). The arrhythmia was recent (< 3 months) in 41% of patients and present for more than one year in 38% of patients. Sixteen patients of Group C (52%) and 11 of Group D (38%) had recurrences after an average of 79 +/- 58 days for Group C and 58 +/- 40 days for Group D (p = NS). The probability of absence of recurrence at 6 months was 36 +/- 11% in Group C and 55 +/- 10% in Group D (p = NS). Four patients in Group C (13%) and 13 patients in Group D (45%) had at least one unwanted side-effect (p = 0.009). Treatment was stopped because of side-effects in 2 patients in group C (6%) and 6 patients in Group D (21%). These results show that cibenzoline has a comparable efficacy for the prevention of recurrence of atrial tachyarrhythmia and is significantly better tolerated than disopyramide. This differences is mainly related to the marked anticholinergic effects of disopyramide.

Aged↗
PubMed1997

Electrophysiological effects of vasoactive intestinal peptide in rabbit atrium: a modulation of acetylcholine activity.

Vasoactive Intestinal Peptide (VIP) is a 28-amino acid peptide partially co-secreted with acetylcholine (Ach) in the atrial tissue. We studied the electrophysiological effects of VIP and Ach in rabbit isolated right atrium by the microelectrode technique. After a 10-min superfusion with VIP, action potential duration at 90% of repolarization (APD90) was lengthened by 23% (P = 0.01) at the concentration of 10(-8) M (n = 10), by 22% (P = 0.004) at 10(-7) M (n = 10) and by 33% (P = 0.03) at 2 x 10(-7) M (n = 5). To explain this APD90 lengthening, we performed 10 other experiments with VIP 10(-7) M, including five preparations pretreated with verapamil (10(-6) M) for 20 min. In the five preparations not pretreated, APD90 was increased by 27% (P = 0.04) after 10 min but remained unchanged in those previously exposed to verapamil, suggesting that VIP is a calcium current activator. Ach (1.4 x 10(-5) M) was superfused in five other experiments and we observed a 31% decrease in APD90 (P= 0.04) at 10 min. After washout, we simultaneously perfused, on the same preparations, Ach (same concentration) and VIP (10(-7) M) for 10 min. The decrease in APD90 (19%) was no longer significant. VIP (2 x 10(-7) M) lengthened cellular effective refractory periods (ERP) by 26% (P = 0.04) after 10 min (n = 5), whereas Ach (1.4 x 10(-5) M) decreased ERP by 33% (P = 0.04) at 10 min (n = 5). In conclusion, VIP lengthens atrial APD90, which may be the result of calcium current activation. In addition, VIP could modulate Ach activity in limiting APD90 shortening in the presence of Ach and because of its opposite effect on atrial ERP. Therefore, VIP could be involved in the control of vagal atrial arrhythmias.

Acetylcholine↗
PubMed1997

[Auricular vulnerability: what information can be obtained from the study of auricular vulnerability? How to perform this study?].

The factors involved in atrial vulnerability are the presence of intra-atrial conduction disorders and abnormalities of refractory periods which are short, dispersed and poorly adapted to heart rate. All these factors are arrthythmogenic. The main value of the study of atrial vulnerability consists of investigation of unexplained ischaemic cerebrovascular accidents in young subjects. In practice, atrial vulnerability can be measured in the context of a classical endocavitary electrophysiological investigation. The stimulation and recording parameters must be standardized. Latent atrial vulnerability can be considered to be present when at least one of the following elements are found: significant inducibility, very short and poorly adapted effective refractory periods, decreased latent atrial vulnerability index.

Atrial Fibrillation↗
PubMed1996

[Mechanisms of atrial fibrillation. Recent progress and therapeutic implications].

Atrial fibrillation is usually due to multiple microreentry circuits. However, in some cases, the initial arrhythmia inducing the atrial fibrillation may be an abnormal automatism, or a macroreentry. The initial abnormalities may induce a desynchronization due to multiple macroreentry circuits. The main factors of atrial vulnerability are intraatrial conduction disturbances and changes in refractory periods. Critical mass and effects of autonomic nervous system may also play a role. Shortened refractory periods and decreased conduction velocity imply a short wavelength and an important arrhythmogenic risk. On the other hand, the longer the duration of atrial fibrillation, the more refractory periods will shorten and the more atrium will become vulnerable: atrial fibrillation tends to beget atrial fibrillation because of an electrophysiologic remodelage. In some cases atrial fibrillation, if its duration is long and if its rate is high, may be responsible for the development of a tachycardiomyopathy. The knowledge of atrial fibrillation mechanism may have interesting therapeutic implications such as resynchronization of the atria by stimulation or ablation, for example in the approaches comparable to the maze operation.

Arrhythmias, Cardiac↗
PubMed1996

Initial and long-term evaluation of escape rhythm after radiofrequency ablation of the AV junction in 50 patients.

Between 1986 and 1994, 50 patients (mean age 63 +/- 13 years), 25 of whom had organic heart disease and presenting with atrial arrhythmias refractory to 5.6 +/- 1.6 antiarrhythmic drugs, underwent radiofrequency ablation (5 +/- 3 pulses by procedure; duration of pulses 50.5 +/- 32 s) of the proximal AV junction to create complete and permanent AV block. The escape rhythm was studied immediately after the procedure and during long-term follow-up. Immediately after the procedure, an escape rhythm was observed in 80% of the patients (junctional in 92%). Over a mean follow-up of 36 +/- 16 months in 47 patients (2 patients died before assessment of escape rhythm and 1 was lost to follow-up), an escape rhythm was present in 39 patients (83%) and absent in the remaining 8 (17%). The only significant difference between the two groups was the initial presence of an escape rhythm (P = 0.008). However, three patients with an initial escape rhythm had none during long-term follow-up. The initial presence of an escape rhythm as a predictive factor of its presence during follow-up had a sensitivity of 87%, specificity of 63%, positive predictive value of 92%, and negative predictive value of 50%. Thus, the absence of an escape rhythm during long-term follow-up causing pacemaker dependency was noted in 1 of 6 patients. This represents a limitation to this palliative treatment, which should be reserved for patients suffering from supraventricular tachycardias refractory to other treatments.

Adult↗
PubMed1996

In vivo assessment of neurotransmitter system in cardiovascular diseases. Clinical issues.

Cardiac neurotransmitter systems, especially the adrenergic receptor pathway, are impaired in heart diseases. In patients with heart failure, these abnormalities contribute to arrhythmogenesis and to progression of cardiac dysfunction. The use of MIBG with single photon imaging has provided useful information on the mechanisms of ventricular arrhythmias, and on the causes of death in patients with heart failure or hypertrophic cardiomyopathy. It has been suggested as a prognostic indicator in patients with heart failure. Positron Emission Tomography (PET) now allows us to obtain noninvasively the quantitative determination of regional receptor density and affinity in humans as well as innervation integrity and functioning. These measurements are based upon the synthesis of a radioligand, usually either a selective receptor antagonist or a false neurotransmitter labeled with a positron-emitting radioisotope. Mathematical compartmental models are fitted to activity-versus-time curves obtained during saturation or displacement experiments in order to calculate the rate constants and the receptor density in the myocardium. PET has only recently begun to be applied to the study of cardiac physiology and disease. PET and SPECT cardiac neuroimaging techniques are able to demonstrate the physiological regulation of receptors, and to provide the possibility of studying regional abnormalities of cardiac neurotransmission, especially in arrhythmogenic cardiomyopathy. Furthermore these non invasive techniques could be useful in exploring the alteration of neurotransmission in the early stage of heart disease and could allow repeated scintigraphic examinations in order to evaluate the effects of cardiac medications.

Animals↗
PubMed1996

[Right precordial leads and sudden death. Relation with arrhythmogenic right ventricular dysplasia].

Non-coronary ST-segment elevation during right sided chest pain has been described in subjects with episodes of ventricular fibrillation at rest. This syndrome has been attributed to functional phenomena or to structural myocardial changes. A personal case has features belonging to two categories: ST-segment elevation observed before, during and after episodes of arrhythmia was compared to 11 previously recorded ECG recordings. Right ventricular dysplasia was shown by electrocardiography, electrophysiology and echocardiography. In addition, ST-segment elevation is classified in 3 categories: triangular and dome-shaped are the most commonly observed forms during the arrhythmias: the third form with "saddle"-shaped appearances has not been previously described and would seem to be a minor equivalent observed during intercritical periods. This form is found in 30% of clinically documented cases of arrhythmogenic right ventricular dysplasia.

Arrhythmias, Cardiac↗
PubMed1995

Comparative behavioural profile of centrally administered tachykinin NK1, NK2 and NK3 receptor agonists in the guinea-pig.

1. The NK1 tachykinin receptor agonists, septide, [Sar9,Met(O2)11]SP and [Pro9]SP produced locomotor hyperactivity (10-20 min) when injected intracerebroventricularly (i.c.v.) in the guinea-pig. The most potent in eliciting this hyperactivity was septide (from 0.63 to 5 micrograms), compared to [Sar9,Met(O2)11]SP, which was active at 2.5 and 5 micrograms and [Pro9]SP which induced a non-significant increase even at 10 micrograms. 2. Wet-dog shakes were elicited by septide, [Sar9,Met(O2)11]SP and [Pro9]SP injected by the i.c.v. route in the guinea-pig. [Sar9,Met(O2)11]SP, active from 0.16 to 2.5 micrograms was more potent than septide (active at 1.25 micrograms) and [Pro9]SP (active at 0.63 micrograms) in eliciting such behaviour. To a lesser extent, grooming was also observed after injection of these agonists. 3. The NK2 tachykinin receptor agonist, [Lys5,MeLeu9,Nle10]NKA(4-10), up to the dose of 10 micrograms i.c.v. had no effect in the guinea-pig. It neither modified locomotor activity nor induced a characteristic behavioural response. At higher doses (20 micrograms), some toxic effects were noted. 4. The NK3 tachykinin receptor agonist, senktide, contrasts with the NK1 receptor agonists in that it elicited only wet-dog shakes, at doses ranging from 0.32 to 1.25 micrograms. It neither modified locomotor activity (1 microgram) nor induced grooming (up to 5 micrograms) in the guinea-pig. 5. To our knowledge, these results are the first demonstration that the guinea-pig could be useful to differentiate tachykinin agonists on the basis of their behavioural profile, distinct from those obtained in mice and rats.

Animals↗
PubMed1995

[Cerebral abscess disclosing tetralogy of Fallot with situs inversus in adulthood].

The authors report the case of tetralogy of Fallot (TOF) associated with situs inversus, the first description of this rare association in a previously asymptomatic adult. A 32 years old chauffeur was admitted to hospital with pyrexia and convulsions due to a left temporo-parietal cerebral abscess which had a favourable outcome. The chest X-ray and Doppler echocardiographic study showed a TOF with a high infundibular stenosis and dextrocardia. Abdominal ultrasonography confirmed a complete situs inversus. The good tolerance was attributed to the equilibrated character of the TOF. The orientation of the heart and the cono-truncal septation occur at different times during embryogenesis. However, there are genetic arguments in favour of the non-fortuitous nature of this association.

Adult↗
PubMed1995

Clinical use of metaiodobenzylguanidine imaging in cardiology.

Cardiac function is predominantly regulated by autonomic innervation. Many heart diseases involve alterations of cardiac adrenergic neurotransmission. In patients with cardiomyopathies, numerous therapeutic agents act directly or indirectly on cardiac adrenergic disorders. Metaiodobenzylguanidine (MIBG) imaging can provide in vivo information on one of the main components of adrenergic nerve function, i.e. the norepinephrine reuptake and storage system. Diminished MIBG uptake has been reported in patients with congestive heart failure, indicating an impaired norepinephrine reuptake and storage system. In patients with dilated cardiomyopathy (either idiopathic or ischemic), this alteration has been linked to the severity of the disease, evaluated on the basis of clinical or hemodynamic parameters. Moreover, MIBG imaging has been reported in such patients to be a potent prognostic marker in comparison with other recognized indices. After myocardial infarction, the decrease in MIBG uptake was transient in some patients and was suggested to be a viability indicator. Diminished MIBG uptake in ischemic patients was linked to the occurrence of ventricular arrhythmias. In patients with primary hypertrophic cardiomyopathy, decreased cardiac MIBG uptake has also been related to the clinical indices of severity. In patients suffering from various arrhythmias such as idiopathic ventricular arrhythmias, arrhythmogenic right ventricular cardiomyopathy or a long-QT syndrome, MIBG imaging has evidenced regional abnormalities of adrenergic nerve function and has provided new insights into the pathophysiological mechanisms of such disorders. Finally, MIBG scintigraphy may permit the evaluation of anthracyclin cardiotoxicity. Thus, MIBG imaging appears to be a promising tool for the cardiologist.

3-Iodobenzylguanidine↗
PubMed1994

CCK-A and CCK-B selective receptor agonists and antagonists modulate olfactory recognition in male rats.

Modulation of learning and memory is one of the physiological roles that the neuropeptide cholecystokinin (CCK-8) may play. We have used a behavioural model of olfactory recognition among rats to test this hypothesis and to explore the relationship between CCK-A and CCK-B receptors and memory retention. Adult male rats form a transient memory of a juvenile congenere as indicated by a reduction in the duration of investigatory behaviour upon re-exposure 30 min after an initial exposure, but not when re-exposure is delayed until 120 min afterwards. In the present study, rats were treated after the first contact with various compounds; inhibition and facilitation of olfactory recognition were evaluated as the persistence in investigation 30 min and the decrease in investigation 120 min after pharmacological manipulations, respectively. Systemic injection of CCK-8, of a selective CCK-A agonist, or of non-peptide CCK-B antagonists (CI-988 and LY-262691) enhanced olfactory recognition. In contrast, the CCK-B selective agonist BC 264 and the tetrapeptide CCK-4 both disrupted it. Taken together with previous evidence of the detrimental effect of the nonpeptide. CCK-A antagonist devazepide on olfactory recognition, these results confirm and extend the hypothesis that there is a balance between CCK-A-mediated facilitative effects and CCK-B-mediated inhibitory effects on memory retention.

Amino Acid Sequence↗
PubMed1993

Altered synaptic plasticity and memory formation in nitric oxide synthase inhibitor-treated rats.

Nitric oxide (NO) is a messenger molecule that is produced in the brain from the metabolism of L-arginine to L-citrulline. Growing evidence suggests a physiological role for NO in long-term potentiation (LTP). Since LTP is a form of synaptic plasticity thought to be involved in learning and memory, we have tested whether inhibition of endogenous NO production affects memory capacities of rats. We found that the NO synthase [L-arginine, NADPH:oxygen oxidoreductase (nitric oxide-forming), EC 1.14.13.39] inhibitor N omega-nitro-L-arginine, at doses blocking LTP in hippocampal slices, impairs spatial learning in a radial arm maze and olfactory memory in a social recognition test. In contrast, N omega-nitro-L-arginine left shock-avoidance learning unaffected. These results indicate that NO is involved in some but not all forms of memory and further support the existence of a causal link between LTP and spatial learning.

Amino Acid Oxidoreductases↗
PubMed1993

New indole derivatives as potent and selective serotonin uptake inhibitors.

A series of new indole derivatives (2-28) has been prepared in the search for novel 5-HT uptake inhibitors. These compounds were obtained by the condensation of N-(chloroalkyl) naphthalenesultam derivatives with the appropriate amine in presence of a base, at reflux of DMF or THF. The yields were moderate (12-56%), except for the piperazine derivative 20 (85%). The affinity of the compounds for uptake site and 5-HT2, alpha 1, and D2 receptors was measured. Some compounds were studied in vivo by their potentiating effect of 5-HTP-induced symptomatology. The most potent and selective (uptake, 5-HT2 versus alpha 1, D2 sites) compounds contain a 3-[(4-piperidinyl)methyl]indole moiety. 5-Fluoro-3-[(4-piperidinyl)methyl]indole itself (compound 1) displayed a high affinity for the uptake site but was devoided of in vivo activity. N-Methylation of this compound abolished the affinity. In contrast N-substitution by a two-carbon chain linked to a naphthalenesultam or related heterocycle led to compounds exhibiting high affinity for the uptake site. One of them, 1-[2-[4-((5-fluoro-1H-indol-3-yl)methyl-1- piperidinyl]ethyl]-5,6-dihydro-1H,4H-1,2,5-thiadiazolo[4,3,2- ij]quinoline 2,2-dioxide (compound 24), was found as active as fluoxetine in vivo.

Animals↗
PubMed1993

RP 59037 and RP 60503: anxiolytic cyclopyrrolone derivatives with low sedative potential. interaction with the gamma-aminobutyric acidA/benzodiazepine receptor complex and behavioral effects in the rodent.

This study describes the pharmacological properties of two novel cyclopyrrolone derivatives, RP 59037 [2-(7-chloro-2-naphthyridin-1,8-yl)-3-(5- methyl-2-oxohexyl)isoindolin-1-one] and RP 60503 [2-(7-chloro-2-naphthyridin-1,8-yl)isoindolin-1-yl-4- acetamidobutyrate], in the rodent. These compounds possess high affinity for the benzodiazepine binding site on the gamma-aminobutyric acidA receptor in rat cerebrocortical membranes with Ki values of 0.98 nM (RP 59037) and 1.16 nM (RP 60503). Neither compound discriminates between the putative benzodiazepine BZ1 and BZ2 binding site subtypes present in the rat cerebellum and hippocampus, respectively. Both compounds protect mice against pentylenetetrazole-induced seizures with ID50 values of 0.21 mg.kg-1 p.o. (RP 59037) and 5.96 mg.kg-1 p.o. (RP 60503). The two compounds displayed a restricted anticonvulsant profile compared to diazepam and, in this respect, resembled the pyrazoloquinoline partial agonist, CGS 9896. RP 59037 and RP 60503 were active in two rat models predictive of anxiolytic drug action, a modified Geller-Seifter conflict paradigm (minimal effective dose, 0.33 mg.kg-1 p.o. for RP 59037 and 5 mg.kg-1 p.o. for RP 60503) and the elevated plus maze (minimal effective dose, 0.33 mg.kg-1 p.o. for RP 59037 and 5 mg.kg-1 p.o. for RP 60503). Only very low activities were observed in tests of sedative or myorelaxant effects (ED50 > 50 mg.kg-1 p.o.). It is concluded that the two cyclopyrrolones possess a dissociated behavioral profile, displaying potent anxiolytic and anticonvulsant properties with little or no sedative or myorelaxant effects. Although both compounds appear to be partial agonists at their allosteric recognition site on the gamma-aminobutyric acidA receptor, RP 60503 seems to be more dissociated than RP 59037, which would be compatible with it having lower intrinsic activity. This difference is reflected in a higher receptor occupancy requirement for activity, and a smaller modulatory effect on the binding of t-[35S]butylbicyclophosphothionate.

Animals↗
PubMed1992

Meningoencephalitis due to penicillin-resistant Streptococcus pneumoniae.

The case of a 68-year-old man suffering from pneumococcal meningoencephalitis is reported. Antibacterial susceptibility tests revealed a multiply resistant pneumococcal strain. High doses of cefotaxime were necessary to sterilize the cerebrospinal fluid despite the achievement of a satisfactory level of antibiotic in the cerebrospinal fluid with moderate dosage. In France, as well as in many countries, high doses of third-generation cephalosporins such as cefotaxime or ceftriaxone should be administered for the initial therapy of suspected pneumococcal meningitis.

Aged↗