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P Poulain

Publications and source records attributed to P Poulain.

At least 37 records · Page 2Linked to original sources
PubMed2000

Decreased susceptibility to diet-induced atherosclerosis in human apolipoprotein A-II transgenic mice.

Studies performed in vivo have been controversial regarding the implication of human apolipoprotein (apo)A-II in the atherogenic process. Expression of human apoA-II in transgenic mice fed a chow diet leads to (1) a bimodal distribution of high density lipoprotein (HDL) size as in humans, (2) a reduction in total cholesterol concentration that is mainly due to a reduction in non-HDL cholesterol level, and (3) a dramatic reduction in mouse endogenous apoA-I and apoA-II. After 20 weeks on an atherogenic diet, transgenic mice had reduced total cholesterol concentrations because of a reduction in cholesterol associated with all lipoprotein classes. Endogenous apoA-I and apoA-II were also dramatically decreased in transgenic mice. The mean area of atherosclerotic lesions was drastically decreased in transgenic mice (-44%, P=0.0027) compared with control mice. The amount of aortic surface covered by lesions was positively correlated with very low density lipoprotein cholesterol (P<0.01) and intermediate density lipoprotein cholesterol levels (P<0.05). Transgenic mice were protected against the development of atherosclerosis despite a marked decrease in HDL cholesterol and apoA-I concentrations. This protection may be related to the marked reduction in circulating low density lipoprotein (very low density and intermediate density lipoprotein) levels in transgenic mice.

Animal Nutritional Physiological Phenomena↗
PubMed2000

[Percutaneous umbilical blood sampling in pregnant women with thrombocytopenia. Apropos of 35 cases].

OBJECTIVE: To determine the interest of percutaneous umbilical blood sampling in maternal thrombocytopenia. PATIENTS AND METHOD: We performed a retrospective study of 36 percutaneous umbilical samples in pregnant women with thrombocytopenia. We included patients with a platelet count less than 100,000/mm(3) or a previous diagnosis of idiopathic thrombocytopenic purpura. Patients were divided into two groups. Group A consisted of women whose thrombocytopenia was caused by idiopathic thrombocytopenic purpura. The other patients were included in the group B. Percutaneous umbilical blood samples were performed by direct ultrasound guidance under sterile conditions, after 37 weeks gestation. Cesarean section was indicated if the fetal platelet count was < or =50 000/mm(3), in other cases obstetric indications were followed. RESULTS: Percutaneous umbilical blood samples were performed at a mean age of 38.5 gestational weeks. Fetal blood sampling was successful in 34 of the 36 cases. There was no fetal complication. In group A, two fetuses had low cord-blood platelet counts (20,000 and 98,000 per cubic millimeter). There was no fetal thrombopenia in group B. Three cesarean sections were performed, in one case because of severe fetal thrombocytopenia and in 2 cases because of an unsuccessful percutaneous umbilical blood sampling (in both, neonatal platelet count was normal). There was no significant complication in infants. There was a significant correlation between fetal and neonatal platelet count. CONCLUSION: There is no maternal predictive factor for fetal thrombocytopenia. Percutaneous umbilical blood sampling is feasible and has a good diagnostic value. The overall risk of fetal loss is low. But there is no indication of percutaneous umbilical blood sampling in the management of thrombocytopenia in pregnancy because severity of thrombopenia is not directly related to the severity of maternal disease and there are no series large enough to assess the association between delivery method and intracranial hemorrhage in thrombocytopenic infants born of mothers with idiopathic thrombocytopenic purpura. More subjectively than on scientific arguments a percutaneous umbilical blood sampling could be performed for patients with idiopathic thrombocytopenia purpura and a past history of neonatal intracranial hemorrhage. A cesarean section could be done if the platelet count is less than 100 000/mm(3), no intracranial hemorrhage has been described above this level.

Cordocentesis↗
PubMed2000

Measurement of apolipoprotein B concentration in plasma lipoproteins by combining selective precipitation and mass spectrometry.

The measurement of apolipoprotein B (apoB) in purified lipoproteins by immunological assays is subject to criticism because of denatured epitopes or immunoreactivity differences between purified lipoproteins and standard. Chemical methods have therefore been developed, such as the selective precipitation of apoB followed by quantification of the precipitate. In this study, we present the measurement of apoB concentration in lipoproteins purified by ultracentrifugation by combining isopropanol precipitation and gas chromatography/mass spectrometry. Very low density lipoprotein (VLDL; d < 1.006 g/mL); VLDL plus intermediate density lipoprotein (VLDL + IDL; d < 1.019 g/mL); and VLDL, IDL, and low density lipoprotein (VLDL + IDL + LDL; d < 1.063 g/mL) were purified by ultracentrifugation. Apolipoprotein B-100 was selectively precipitated by isopropanol. The leucine content of the pellet was then determined by gas chromatography/mass spectrometry, using norleucine as internal standard. Knowledge of the number of leucine molecules in one apoB-100 molecule makes it possible to calculate the plasma concentration of apoB in the various lipoprotein fractions. ApoB in IDL (d 1.006-1.019 g/mL) and LDL (d 1.019-1.063 g/mL) were then determined by subtracting VLDL-apoB from apoB in lipoproteins d < 1.019 and apoB in lipoproteins d < 1.019 g/mL from apoB in lipoproteins d < 1.063 g/mL, respectively. The isopropanol precipitate was verified as pure apoB (>97%) in lipoprotein fractions isolated from normo- and hyperlipidemic plasma and the method appeared reproducible. The combination of isopropanol precipitation and the GC/MS method appears therefore to be a precise and reliable method for kinetic and epidemiological studies.

2-Propanol↗
PubMed1999

[Care of children at the end of life].

Palliative care in children at the end of life should associate the family, the general practitioner, and the hospital team. The care of pain is especially important, with some specific aspects in children. Drug treatments are better precised. Non drug treatments have an increasing role for treating pain in children. Recommendations for palliative care in children with cancer have been established.

Adolescent↗
PubMed1999

Beneficial effects of fibrates on apolipoprotein A-I metabolism occur independently of any peroxisome proliferative response.

BACKGROUND: In humans, fibrates are frequently used normolipidemic drugs. Fibrates act by regulating genes involved in lipoprotein metabolism via activation of the peroxisome proliferator-activated receptor-alpha (PPARalpha) in liver. In rodents, however, fibrates induce a peroxisome proliferation, leading to hepatomegaly and possibly hepatocarcinogenesis. Although this peroxisome proliferative response appears not to occur in humans, it remains controversial whether the beneficial effects of fibrates on lipoprotein metabolism can occur dissociated from such undesirable peroxisomal response. Here, we assessed the influence of fenofibrate on lipoprotein metabolism and peroxisome proliferation in the rabbit, an animal that, contrary to rodents and similar to humans, is less sensitive to peroxisome proliferators. METHODS AND RESULTS: First, we demonstrate that in normal rabbits, fenofibrate given at a high dose for 2 weeks does not influence serum concentrations or intestinal mRNA levels of the HDL apolipoprotein apoA-I. Therefore, the study was continued with human apoA-I transgenic rabbits that overexpress the human apoA-I gene under control of its homologous promoter, including its PPAR-response elements. In these animals, fenofibrate increases serum human apoA-I concentrations via an increased expression of the human apoA-I gene in liver. Interestingly, liver weight or mRNA levels and activity of fatty acyl-CoA oxidase, a rate-limiting and marker enzyme of peroxisomal beta-oxidation, remain unchanged after fenofibrate. CONCLUSIONS: Expression of the human apoA-I transgene in rabbit liver suffices to confer fibrate-mediated induction of serum apoA-I. Furthermore, these data provide in vivo evidence that the beneficial effects of fibrates on lipoprotein metabolism occur mechanistically dissociated from any deleterious activity on peroxisome proliferation and possibly hepatocarcinogenesis.

Acyl-CoA Oxidase↗
PubMed1999

Fibrates suppress fibrinogen gene expression in rodents via activation of the peroxisome proliferator-activated receptor-alpha.

Plasma fibrinogen levels have been identified as an important risk factor for cardiovascular diseases. Among the few compounds known to lower circulating fibrinogen levels in humans are certain fibrates. We have studied the regulation of fibrinogen gene expression by fibrates in rodents. Treatment of adult male rats with fenofibrate (0.5% [wt/wt] in the diet) for 7 days decreased hepatic Aalpha-, Bbeta-, and gamma-chain mRNA levels to 52% +/- 7%, 46% +/- 8%, and 81% +/- 19% of control values, respectively. In parallel, plasma fibrinogen concentrations were decreased to 63% +/- 7% of controls. The suppression of fibrinogen expression was dose-dependent and was already evident after 1 day at the highest dose of fenofibrate tested (0.5% [wt/wt]). Nuclear run-on experiments showed that the decrease in fibrinogen expression after fenofibrate occurred at the transcriptional level, as exemplified for the gene for the Aalpha-chain. Other fibrates tested showed similar effects on fibrinogen expression and transcription. The effect of fibrates is specific for peroxisome proliferator-activated receptor-alpha (PPARalpha) because a high-affinity ligand for PPARgamma, the thiazolidinedione BRL 49653, lowered triglyceride levels, but was unable to suppress fibrinogen expression. Direct evidence for the involvement of PPARalpha in the suppression of fibrinogen by fibrates was obtained using PPARalpha-null (-/-) mice. Compared with (+/+) mice, plasma fibrinogen levels in (-/-) mice were significantly higher (3.20 +/- 0.48 v 2.67 +/- 0.42 g/L). Also, hepatic fibrinogen Aalpha-chain mRNA levels were 25% +/- 11% higher in the (-/-) mice. On treatment with 0.2% (wt/wt) fenofibrate, a significant decrease in plasma fibrinogen to 77% +/- 10% of control levels and in hepatic fibrinogen Aalpha-chain mRNA levels to 65% +/- 12% of control levels was seen in (+/+) mice, but not in (-/-) mice. These studies show that PPARalpha regulates basal levels of plasma fibrinogen and establish that fibrate-suppressed expression of fibrinogen in rodents is mediated through PPARalpha.

Animals↗
PubMed1999

Properties of T-type calcium current in enkephalinergic neurones in guinea-pig hypothalamic slices.

The guinea-pig hypothalamic magnocellular dorsal nucleus (mdn) exclusively contains enkephalinergic neurones providing inputs to the septum. This nucleus is believed to play a role in hippocampo-septo-hypothalamic relationships. mdn neurones display prominent low-threshold Ca2+ spikes, which differ in their propensity to trigger either a burst of Na+ spikes or a single spike. In the present study, whole-cell voltage-clamp experiments were carried out on thick slices at 34 degrees C to characterize the pharmacological and physical properties of the transient Ca2+ current (IT) underlying the low-threshold spikes. Recorded cells were dye-labelled and identified as belonging to the mdn. In bursting and non-bursting neurones, IT was reduced by amiloride (1 microM) and octanol (1 mM), and during replacement of Ca2+ by Ba2+. The Ca2+ channel blocker mibefradil (10 microM) had only a slight blocking action. Nifedipine (100 microM) and flunarizine (1 microM) had no effect. IT activated between -80 mV and -50 mV and the mean peak current was 1050 pA. Steady-state activation and inactivation curves were fitted by a Boltzmann equation. The half-activation voltage was -70 mV, slope factor=3.6, and half-inactivation voltage was about -80 mV, slope factor=4.5. Time-to-peak and time constant of inactivation were voltage dependent. Recovery from activation occurred within 500 ms. When compared with results on other IT, the present data show that the current possesses distinct pharmacological and physical properties. Nevertheless, all investigated cells displayed a homogenous profile of IT, suggesting that the differences in spike pattern between mdn neurones are not due to different populations of Ca2+ channels.

Amiloride↗
PubMed1999

Projections of the mediolateral part of the lateral septum to the hypothalamus, revealed by Fos expression and axonal tracing in rats.

The lateral septum participates in a variety of functions involving the hypothalamus. The present study investigated the effect of an electrical stimulation of the mediolateral part of the lateral septum on the expression of Fos in the hypothalamic nuclei by using immunohistochemical methods in anaesthetised and free-moving rats. We analysed in another series of rats the direct projections of the lateral septum by axonal anterograde tracing with biotinylated dextran-amine. Tracing was used in combination with Fos labelling in a third series of animals. Stimulation induced an expression of Fos in neurones located in anteroventral and anterodorsal preoptic nuclei, medial preoptic area, anterior hypothalamic nucleus, subparaventricular zone, dorsomedial nucleus, lateral hypothalamic area and mammillary nucleus. The distribution of Fos-immunoreactive neurones conforms to the topographic organisation of direct projections from the lateral septum, as revealed by axonal tracing. These results suggest that the lateral septum activates definite hypothalamic structures by a direct link. Some structures displayed substantial Fos labelling whereas they received a slight, or no projection, from the lateral septum. This was particularly evident in the core of the ventromedial nucleus and in areas known to contain tubero-infundibular neurones. This observation suggests that the lateral septum may also exert an indirect control, via polysynaptic links, on hypothalamic structures including nuclei involved in neuroendocrine mechanisms.

Animals↗
PubMed1999

Pregnancy-associated autoimmune neonatal thrombocytopenia: role of maternal HLA genotype.

In a prospective study between 1993 and 1998, data was collected from 46 pregnant women and subsequently from their babies. 25 pregnant women with active autoimmune thrombocytopenic purpura (AITP) or a history of AITP (group A) and 21 pregnant women with isolated thrombocytopenia and identification of specific platelet autoantibodies detected by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay (group B) were evaluated for platelet-associated immunoglobulin-G (PAIgG), MAIPA assay and HLA genotype. Neonatal platelet counts were performed at least three times in the first week. 11 neonates were thrombocytopenic (23.9%). No severe haemorrhage occurred. There were no significant differences regarding the values of PAIgG or positive MAIPA tests between mothers of thrombocytopenic or healthy newborns. A significant difference, however, regarding the HLA DRB3* allele was found, with a high incidence in the subgroup of mothers of healthy newborns (P = 0.005). A similar trend was found among mothers with anti-GPIIbIIIa antibodies (P = 0.06). In contrast, HLA DRB5* allele appeared to be present especially in mothers of thrombocytopenic newborns (not significant). Our data suggest that mothers with AITP who have the HLA DRB3* genotype are unlikely to give birth to a thrombocytopenic baby. This study provides a preliminary report on a noninvasive test to identify infants who are likely to be affected.

Autoantibodies↗
PubMed1999

Estradiol coupling to endothelial nitric oxide stimulates gonadotropin-releasing hormone release from rat median eminence via a membrane receptor.

The median eminence (ME), which is the common termination field for adenohypophysiotropic systems, has been shown to produce nitric oxide (NO), a signaling molecule involved in neuroendocrine secretion. Using an ex vivo technique, 17beta-estradiol exposure to ME fragments, including vascular tissues, stimulated NO release within seconds in a concentration-dependent manner, whereas 17alpha-estradiol or testosterone had no effect. 17Beta-estradiol conjugated to BSA (E2-BSA) also stimulated NO release, suggesting mediation by a membrane surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized the action of both 17beta-estradiol and E2-BSA. Furthermore, estradiol-stimulated NO stimulates GnRH release. This was demonstrated by hemoglobin (a NO scavenger), N(omega)-nitro-L-arginine methyl ester, and L-N5-(1-iminoethyl)ornithine (nitric oxide synthase inhibitors) inhibition of estradiol stimulated NO and GnRH release. In this regard, L-N5-(1-iminoethyl)ornithine, specific for endotheliol constitutive nitric oxide synthase, was significantly more potent, suggesting that the estradiol-stimulated NO release arose from vascular endothelial cells. Additionally, the NO-stimulated GnRH release occurs via guanylyl cyclase activation in GnRH nerve terminals, as ODQ, a potent and selective inhibitor of NO-sensitive guanylyl cyclase, abolished the estradiol-stimulated GnRH release. The results suggest that at physiological concentrations, 17beta-estradiol may have immediate actions on ME endothelial cells via nongenomic signaling pathways leading to NO-stimulated GnRH release.

Animals↗
PubMed1999

[Multicystic neonatal encephalopathy after a traffic accident with minor maternal injuries].

We report a case of traffic accident at 30 weeks of gestation. The maternal injuries were minor. The fetal heart rate patterns showed tachycardia and decreased modulation. Ultrasound scanning was normal, without abruptio placentae. Ten days after the accident, a cesarean section was done on altered fetal heart rate with a normal infant at birth. This baby died 17 days latter from an ischemic multicystic encephalomalacia. With the view of the literature, we try to explain the pathophysiological mechanism of this severe fetal outcome despite minor maternal injuries. Hypovolemic collapsus, caval syndrome and maternal stress could be the cause of placental hypoperfusion. Abruptio placenta and feto-placental hemorrhage are others explanations. We propose the management for first aid workers and the specialized unit care.

Accidents, Traffic↗
PubMed1999

[Nuchal translucency: screening for chromosomal abnormalities and congenital malformations. Multicenter study].

OBJECTIVE: To value the rate of chromosomal abnormalities and evolution of children who had a prenatal diagnosis of fetal nuchal translucency in the first trimester. MATERIAL AND METHODS: Multicenter prospective study conducted in 4,582 patients who had a first ultrasonography between 10 and 14 weeks' gestation (abdominal and/or transvaginal sonography). The measurement of fetal nuchal translucency was performed by mid-sagittal section and when it was higher than 2.5 mm a fetal karyotype was made. RESULTS: Three hundred and fifty eight nuchal translucencies (> 2.5 mm) were diagnosed and 334 karyotypes were done. We found 25 chromosomal anomalies (7.4%): 14 trisomies 21; 7 trisomies 18; 2 trisomies 13; one triploidy and one trisomy X. The postnatal examination of children detected three congenital malformations (0.9%): one facial dysmorphia, one complex abnormal heart anatomy and one renal agenesia. CONCLUSION: Nuchal translucency (> 2.5 mm) is therefore a sonography sign associated with 7.4% of chromosomal anomalies. The distribution by size and mother ages is low. It should need superior larger-scale studies are needed for representative data. But this study shows that if fetal karyotype is normal, the incidence of congenital malformations seems to be the same by comparison with the general population.

Chromosome Aberrations↗
PubMed1998

Distribution of cortical fibers and fos immunoreactive neurons in ventrolateral medulla and in nucleus tractus solitarius following the motor cortex stimulation in the rat.

The present study demonstrates that the motor cortex (MC) stimulation induces expression of Fos-like immunoreactivity (FLI) in the rostro-caudal parts of ventrolateral medulla (VLM) and nucleus tractus solitarius (NTS). The coupling of biotinylated dextran (BD) injections with the MC stimulation also permits to identify cortical labeled fibers in the vicinity of FLI neurons in the VLM. Results suggest that the MC is involved in a direct and an indirect modulation of bulbar cardiovascular nuclei.

Animals↗
PubMed1998

Morphine and anandamide coupling to nitric oxide stimulates GnRH and CRF release from rat median eminence: neurovascular regulation.

Nitric oxide (NO) is involved in neurohormonal secretion from median eminence neuroendocrine nerve terminals. We report that stimulation of NO release from median eminence fragments including vascular tissues occurs by mu3 receptor activation by morphine, or by cannabinoid type 1 receptor activation by anandamide. The released levels of NO are lower after anandamide than after morphine stimulation. These processes can be blocked by L-NAME, a specific nitric oxide synthase inhibitor, by naloxone for the morphine-stimulated NO release, or SR 141716A, a specific CB1 receptor inhibitor, for the anandamide-stimulated NO release. Furthermore, morphine and anandamide, by this NO dependent process, influences neurohormonal release from median eminence nerve terminals within 10 min. Via this NO dependent process, morphine stimulates both GnRH and CRF release, whereas anandamide selectively stimulates GnRH release. These observations together with previous data suggest that morphine and the anandamide-stimulated NO originates from the vascular endothelium of the portal plexus. These results indicate that endothelial cells of the median eminence may be involved in the release of neurohormones.

Animals↗
PubMed1998

High prevalence of cervical intra-epithelial neoplasia in women treated for pelvic inflammatory disease.

Because human papillomavirus (HPV) is sexually transmitted, as are pelvic inflammatory disease (PID) agents, the authors investigated whether cervical intra-epithelial neoplasia (CIN) are more frequent in women under treatment for PID. The study involved 298 patients hospitalized for PID, in whom CIN were investigated by smears and colposcopy. CIN were diagnosed in 42 patients, i.e. in 14% of patients: 21 low-grade CIN and 21 high-grade CIN, including one case of early-stage microinvasion. These figures are to be compared to the 0.5-4% of pre-cancerous lesions found in the general population. Screening smears are frequently inaccurate and direct colposcopy appeared preferable. No clinical study of this type has been published before, but certain authors have mentioned a high CIN incidence in patients with PID histories or followed up in sexually transmitted disease centers. These results show that CIN are more frequent in patients treated for PID; CIN should be investigated systematically in this population.

Adolescent↗
PubMed1998

Transdermal fentanyl for pain control in adults with chronic cancer pain.

The transdermal therapeutic system (TTS) for fentanyl is a drug-delivery system for use in patients with chronic pain who require an opioid analgesic. A multicentre, randomized, double-blind, placebo-controlled study was performed to evaluate the efficacy and safety of TTS-fentanyl as an analgesic for chronic cancer pain. One hundred and thirty-eight patients entered a 15-day dose-titration period, followed by a 9-day double-blind period (95 patients) with TTS-fentanyl or placebo. Fifty-five patients entered a follow-up period of indefinite duration. For the majority of patients, TTS-fentanyl 50-75 µg/h provided effective analgesia. Due to an unexpectedly high placebo response, it was not possible to show fentanyl to be statistically superior to placebo at the 5% significance level. Nine patients treated with fentanyl and 13 treated with placebo were withdrawn from the study during the double-blind therapy because of insufficient efficacy (not significant), while 66% of fentanyl-treated patients experienced effective pain control compared with 48% of placebo-treated patients (p=0.071). During the course of the double-blind therapy, the mean dose of rescue morphine increased slightly more in the placebo group than in the fentanyl group. At the end of the double-blind phase, the investigators rated trial medication as being 'good' or 'excellent' in 30 patients in the fentanyl group and 23 in the placebo group. TTS-fentanyl appeared to be well tolerated, with a low incidence of constipation, somnolence and nausea. Due to an unexpectedly high placebo response it was not possible to demonstrate fentanyl to be statistically superior to placebo. This may reflect the practical difficulties of performing clinical trials in cancer patients with great inter-individual variability. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗
PubMed1998

[Agenesis of the corpus callosum. An example of prognosis uncertainty in fetal medicine].

OBJECTIVE: For an increasing number of fetal pathologies, means of diagnosis have progressed faster than knowledge of the prognosis. Decisions are extremely difficult for the medical staff and the parents each time that outcome is uncertain. Agenesis of the corpus callosum, whose diagnosis may be certain through ultrasonography and MRI illustrates this situation well. METHODS: A historical multicentric study enabled us to analyze 37 cases of agenesis of the corpus callosum with a prenatal diagnosis and 10 cases with a post-natal one. RESULTS: Among the 37 prenatal diagnoses, we found 28 cases of medical abortions according to the French law and 9 newborns. Among the 9 newborns, we observed one neonatal death related to an acute fetal distress and 3 post-natal deaths between 1 and 3 months. Among the 10 cases diagnosed after birth, one died, 7 are in good health with a follow-up from 7 months to 6 years and 2 have neurological disturbances. CONCLUSION: Therefore, it seems essential to deepen knowledge of the prognosis and the evolutivity of this affliction in order to give the parents more precise information. However, knowledge of the prognosis is difficult because of the large number of abortions performed for medical reasons. Only a multicentric study, with a long-term pediatric follow-up, will enable us to better understand the prognosis of corpus callosum agenesis.

Agenesis of Corpus Callosum↗