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Biomedical subjects

P Petit

Publications and source records attributed to P Petit.

At least 73 records · Page 4Linked to original sources
PubMed1999

2-thioether 5'-O-(1-thiotriphosphate)adenosine derivatives as new insulin secretagogues acting through P2Y-Receptors.

P2-Receptors (P2-Rs) represent significant targets for novel drug development. P2-Rs were identified also on pancreatic B cells and are involved in insulin secretion. Therefore, novel P2Y-R ligands, 2-thioether 5'-O-phosphorothioate adenosine derivatives (2-RS-ATP-alpha-S), were synthesized as potential insulin secretagogues. An efficient synthesis of these nucleotides and a facile method for separation of the chiral products are described. The enzymatic stability of the compounds toward pig pancreas type I ATPDase was evaluated. The rate of hydrolysis of 2-hexylthio-5'-O-(1-thiotriphosphate)adenosine (2-hexylthio-ATP-alpha-S) isomers by ATPDase was 28% of that of ATP. Some 2-thioether 5'-(monophosphorothioate)adenosine derivatives (2-RS-AMP-S) exerted an inhibitory effect on ATPDase. The apparent affinity of the compounds to P2Y(1)-R was determined by measurement of P2Y-R-promoted phospholipase C activity in turkey erythrocyte membranes. 2-RS-ATP-alpha-S derivatives were agonists, stimulating the production of inositol phosphates with K(0.5) values in the nanomolar range. 2-RS-AMP-S derivatives were full agonists, although 2 orders of magnitude less potent. All the compounds were more potent than ATP. The effect on insulin secretion and pancreatic flow rate was evaluated on isolated and perfused rat pancreas. A high increase, up to 500%, in glucose-induced insulin secretion was due to addition of 2-hexylthio-ATP-alpha-S in the nanomolar concentration range, which represents 100-fold enhancement of activity relative to ATP. 2-Hexylthio-AMP-S was 2.5 orders of magnitude less effective.

Adenosine↗
PubMed1999

Contrasting effects of streptozotocin-induced diabetes on the in vitro relaxant properties of adenosine in rat pancreatic vascular bed and thoracic aorta.

In the present work, we have studied adenosine-induced vasodilation in streptozotocin-induced diabetic rats and compared it to that observed in normal age-matched or weight-matched animals. Experiments were performed on a vascular bed, the isolated perfused pancreas, and a large vessel, the thoracic aorta, provided from the same animal. Vasodilator activity was assessed, for isolated pancreas, as the increase in flow induced by the infusion of 2 microM adenosine for 30 min, or for noradrenaline-contracted aortae, as the relaxant response to adenosine (1 microM-1 mM). In both preparations the results obtained with selective adenosine receptors ligands (CPA, CGS 21680 and NECA) agreed with the presence of adenosine receptor of A2a subtype. In normal animals, adenosine vasodilator activity on both preparations diminished with advancing age in the rat, while diabetes was associated with a decreased or increased responsiveness to adenosine in pancreatic vascular bed or aorta, respectively. Further, the involvement of nitric oxide (NO), in relaxant responses, was evaluated by the use of the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). In all groups of animals, the flow rate of isolated pancreas dropped in the presence of 200 microM L-NAME, but was restored by adenosine to the level observed without L-NAME. L-NAME (10 microM) significantly reduced the dilator response to adenosine in aortic rings from diabetic animals, but not in those from normal rats. These results showed that adenosine vasorelaxant activity is significantly but differentially altered by diabetes according to the origin of the vascular preparation, and suggest that NO is involved in the vasorelaxant activity of adenosine in large vessels of diabetic animals. The potential pathophysiological role of adenosine in the vascular complications of diabetes remains to be determined.

Adenosine↗
PubMed1999

Pulmonary anthracosis in children.

We report two cases of children with malignancies and subpleural nodules found on computed tomography (CT) scan. In both cases the diagnosis was anthracosis. This pathologic condition has never been reported in children. Causes of anthracosis include a smoking environment, living in urban areas and air pollution.

Air Pollutants↗
PubMed1999

Multiple small accessory marker chromosomes from different centromeric origin in a moderately mentally retarded male.

The occurrence of more than two small accessory chromosomes (SACs) in a single individual is extremely rare. Here, we characterize six SACs found in the cells of two different tissues of a moderately mentally retarded male. Microdissection combined with regular FISH demonstrates that the SACs are ring chromosomes derived from the centromeres of different chromosomes. The SACs are often associated with the centromeres of other chromosomes. Immunofluorescence with an anti-CENP-C antibody demonstrates that the SACs contain an active centromere. A possible mechanism by which the SACs originated and their clinical relevance are discussed.

Centromere↗
PubMed1999

[Severe head injuries: effects of pre-hospital mechanical ventilation on capnia].

OBJECTIVE: To assess the effect on PaCO2 of mechanical ventilation during prehospital management of severely head-injured patients. STUDY DESIGN: Retrospective observational study. PATIENTS: Severely head-injured patients with Glasgow coma score < or = 8. All patients were sedated, with the trachea intubated and the lungs mechanically ventilated. METHODS: According to the capnia measured at the admission in the neurosurgical intensive therapy unit they were allocated into one of the following three groups: hypocapnia group (PaCO2 < 30 mmHg), recommended capnia group (PaCO2 = 30-38 mmHg) and hypercapnia group (PaCO2 > 38 mmHg). RESULTS: Out of the 42 patients with similarly severe head injuries, 19% were included in the recommended capnia group (PaCO2: 34 +/- 2 mmHg), 38% in the hypocapnia group (PaCO2: 23 +/- 3 mmHg) and 43% in the hypercapnia group (PaCO2: 47 +/- 7 mmHg). In all except three, PaO2 was above 95 mmHg. The settings of ventilatory parameters on the ventilators were similar. CONCLUSION: In 81% of patients, mechanical ventilation was inadequate as far as PaCO2 levels are concerned. Major hypocapnia and hypercapnia carry a potential risk for cerebral ischaemic. Therefore it is recommended to monitor PETCO2 during prehospital transport in medical ambulances and to determine arterial blood gases at arrival of severely head-injured patients in the admission unit for emergencies.

Adolescent↗
PubMed1999

Overdose with sustained-release lithium preparations.

Acute lithium intoxication is potentially lethal. Compared to conventional lithium preparations, sustained-release lithium formulations present specific problems for medical practice in the case of overdose. We report a case of intoxication with 8000 mg of sustained-release lithium carbonate preparation (Teralithe 400 LP(R)). Twenty-five hours after the ingestion, the patient was still asymptomatic, despite a serum level in the toxic range. After comparison of this case with reports found in the Medline database, we consider the clinical management of such cases.

Adult↗
PubMed1999

4-Hydroxyisoleucine: experimental evidence of its insulinotropic and antidiabetic properties.

We have recently shown in vitro that 4-hydroxyisoleucine (4-OH-Ile), an amino acid extracted from fenugreek seeds, potentiates insulin secretion in a glucose-dependent manner. The present study was designed to investigate whether 4-OH-Ile could exert in vivo insulinotropic and antidiabetic properties. For this purpose, intravenous or oral glucose tolerance tests (IVGTTs and OGTTs, respectively) were performed not only in normal animals but also in a type II diabetes rat model. During IVGTT in normal rats or OGTT in normal dogs, 4-OH-Ile (18 mg/kg) improved glucose tolerance. The lactonic form of 4-OH-Ile was ineffective in normal rats. In non-insulin-dependent diabetic (NIDD) rats, a single intravenous administration of 4-OH-Ile (50 mg/kg) partially restored glucose-induced insulin response without affecting glucose tolerance; a 6-day subchronic administration of 4-OH-Ile (50 mg/kg, daily) reduced basal hyperglycemia, decreased basal insulinemia, and slightly, but significantly, improved glucose tolerance. In vitro, 4-OH-Ile (200 microM) potentiated glucose (16.7 mM)-induced insulin release from NIDD rat-isolated islets. So, the antidiabetic effects of 4-OH-Ile on NIDD rats result, at least in part, from a direct pancreatic B cell stimulation.

Acids↗
PubMed1999

[Is ultrasonographic evaluation the the length of the kidney possible in children? Apropos of a prospective study in Madagascar children less than 1 year of age].

Renal US was prospectively performed in 124 madagascan children less than 1 year of age. Patients were examined in the prone position and maximum kidney length was measured in the longitudinal plane. These measurements and the height and weight of our patient population were compared to published tables. Kidney length and height and weight of our patient population were inferior to the previously published reference data and the growth curve of kidneys steeper than normative standards (p < 0.001). Because of the important variability in US measurement of kidney length it is not possible to definitely conclude that length and growth curve of kidneys in madagascan children are statistically different from those of the published normative standards.

Age Factors↗
PubMed1999

[Use of polydimethylsiloxane in the endoscopic treatment of urinary incontinence of neurologic origin in children].

AIM: We report the use of polydimethylsiloxane (PDS-Macroplastique) in endoscopic treatment of urinary incontinence in children with neurogenic bladder and try to determine optimal criteria for patient selection. METHODS: Forty four children (19 males, 25 females) have been treated since 1995. Aetiology was mainly spina bifida (n = 36). Previous surgery had been performed in 26 patients, including bladder neck reconstruction in 21 cases and bladder augmentation in 15 cases. Mean age at injection was 13 years (7 to 17). Only one injection was performed in 27 patients, two injections in 4 cases, and three and more injections in 3 cases. Mean volume at each injection was 3.6 cc. Mean interval between two injections was 6 months (3-15 m). All injections were performed transurethrally. RESULTS: Follow-up ranged from 6 to 41 months (median: 23). Fifteen patients (34%) are dry (continence > 4 hours, no urinary pad during the day) and 11 (25%) are improved (continence from 2 to 3 hours, minimal pad). Eighteen patients obtained poor results. In the entire series previous bladder neck surgery or preoperative detrusor hyperactivity did not interfere with the results. The only difference concerns the sex-ratio: the good results were mainly seen in females: 44% of girls are cured versus 21% of boys. CONCLUSION: Injection of PDS in the bladder neck achieve the goal of continence in 34% of the cases in neurogenic bladder. Better results are seen in girls. Injection does not compromise other surgical procedures. The use of PDS seems more suitable than bovine collagen in view of the potential problems of prions.

Adolescent↗
PubMed1999

[Involvement of P2X and P2U receptors in the constrictor effect of ATP on the pancreatic vascular bed].

The effects of ATP on the pancreatic vascular bed were studied on the isolated rat pancreas perfused at a constant pressure so as any change in the vascular tone induces a modification in the flow rate. This study was performed in two different experimental conditions: 1) In the presence of indomethacin, inhibiting the cyclo-oxygenase and prostacyclin (PGI2) synthesis, ATP (which acts on vasodilatator P2Y receptors and vasoconstrictor P2X and P2U receptors) was used at a concentration (165 microM) which did not modify per se the vascular flow rate. With indomethacin, ATP induced a slight but significant and long lasting decrease in the flow rate. This effect is different from that induced by the stimulation of P2X receptors; it is comparable to that induced by the activation of P2U receptors. 2) In the presence of 2,2'pyridylisatogen tosilate (PIT) used at two different concentrations, the first (5 microM) inhibiting the P2Y effects on insulin secreting B cells and pancreatic vessels, the second (25 microM) inhibiting the P2X effects on pancreatic vessels. The effects of ATP are different according to the concentration of PIT. In both cases, ATP induced only a vasoconstriction. However, the kinetics of the flow rate is totally different: in the presence of 5 microM PIT, an immediate and drastic vasoconstriction was observed, followed by a long lasting vasoconstriction of lesser magnitude, which can be ascribed to P2X and P2U receptor activation, respectively. This hypothesis was confirmed by the results in the presence of PIT at 25 microM. At this concentration this compound completely suppressed the drastic and transient vasoconstriction, so that only a progressive and long lasting vasoconstriction of the P2U type could be observed. From these results, it can be concluded that: 1) PGI2 plays a part in the vasodilatator effects of ATP. 2) At the concentrations used, PIT does not block the vasoconstriction induced by P2U receptors. 3) The effects of ATP on pancreatic vessels is dependent on the balance between its vasodilator effect due to the activation of P2Y receptors and its vasoconstrictor effect which involves two types of receptors: P2X and P2U.

Adenosine Triphosphate↗
PubMed1999

[Sudden cardiac death: the chain of survival in France].

In 1991 the concept of chain of survival was widely accepted. In France, one of the main difficulties was to perform early defibrillation. Only physicians were authorized to use defibrillators and the survival rate was not better than 1 to 2%. In 1991, a prospective study was initiated by the SAMU in Lyon and extended in Paris and Lille to assess the improvement afforded by the use of automatic external defibrillators (AED) by firemen. In this study, time to defibrillation was divided by two (8 to 10 min). Over the six years period of the study, firemen applied AEDs on 877 patients suffering from non traumatic cardiac arrest, 36.1% of them were in ventricular fibrillation (VF) after the simultaneous intervention of firemen and medicalized Mobile Intensive Care Units. The global survival rate of all the patients improved from 2 to 6.2% and from 1.5% to 3.4% for patients without neurological impairment (p < 0.01). The survival rate of the 317 FV was 15.1% (9.5% without neurological impairment). This results are encouraging but not sufficient. Since 1998, AED can be legally used by non physicians professionals, but the others links of the chain have to be improved, particularly by educating the public.

Adolescent↗
PubMed1998

A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European Epinephrine Study Group.

BACKGROUND: Clinical trials have not shown a benefit of high doses of epinephrine in the management of cardiac arrest. We conducted a prospective, multicenter, randomized study comparing repeated high doses of epinephrine with repeated standard doses in cases of out-of-hospital cardiac arrest. METHODS: Adult patients who had cardiac arrest outside the hospital were enrolled if the cardiac rhythm continued to be ventricular fibrillation despite the administration of external electrical shocks, or if they had asystole or pulseless electrical activity at the time epinephrine was administered. We randomly assigned 3327 patients to receive up to 15 high doses (5 mg each) or standard doses (1 mg each) of epinephrine according to the current protocol for advanced cardiac life support. RESULTS: In the high-dose group, 40.4 percent of 1677 patients had a return of spontaneous circulation, as compared with 36.4 percent of 1650 patients in the standard-dose group (P=0.02); 26.5 percent of the patients in the high-dose group and 23.6 percent of those in the standard-dose group survived to be admitted to the hospital (P=0.05); 2.3 percent of the patients in the high-dose group and 2.8 percent in the standard-dose group survived to be discharged from the hospital (P=0.34). There was no significant difference in neurologic status according to treatment among those discharged. High-dose epinephrine improved the rate of successful resuscitation in patients with asystole, but not in those with ventricular fibrillation. CONCLUSIONS: In our study, long-term survival after cardiac arrest outside the hospital was no better with repeated high doses of epinephrine than with repeated standard doses.

Adrenergic Agonists↗
PubMed1998

De novo 7q36 deletion: breakpoint analysis and types of holoprosencephaly.

We report on a de novo 7q36 deletion in a 3-month-old girl with manifestations of the 7q terminal deletion syndrome. Only minimal findings of holoprosencephaly (HPE) were present since only a partial corpus callosum hypoplasia was seen on a magnetic resonance imaging scan of the brain. Extensive fluorescence in situ hybridization analysis showed that the HPE3 critical gene region, inclusive Sonic hedgehog (SHH), En2 (HOX1), and HTR5A, was deleted. A review of 33 other patients with a de novo terminal 7q deletion and the different types of HPE manifestations within these patients will be presented.

Brain↗