Rate of caesarean sections according to the Robson classification: Analysis in a French perinatal network - Interest and limitations of the French medico-administrative data (PMSI).

INTRODUCTION: The objective of our study was to determine, in accordance with WHO recommendations, the rates of Caesarean sections in a French perinatal network according to the Robson classification and determine the benefit of the medico-administrative data (PMSI) to collect this indicator. This study aimed to identify the main groups contributing to local variations in the rates of Caesarean sections. MATERIAL AND METHODS: A descriptive multicentric study was conducted in 13 maternity units of a French perinatal network. The rates of Caesarean sections and the contribution of each group of the Robson classification were calculated for all Caesarean sections performed in 2014. The agreement of the classification of Caesarean sections according to Robson using medico-administrative data and data collected in the patient records was measured by the Kappa index. We also analysed a 6 groups simplified Robson classification only using data from PMSI, which do not inform about parity and onset of labour. RESULTS: The rate of Caesarean sections was 19% (14.5-33.2) in 2014 (2924 out of 15413 deliveries). The most important contributors to the total rates were groups 1, 2 and 5, representing respectively 14.3%, 16.7% and 32.1% of the Caesarean sections. The rates were significantly different in level 1, 2b and 3 maternity units in groups 1 to 4, level 2a maternity units in group 5, and level 3 maternity units in groups 6 and 7. The agreement between the simplified Robson classification produced using the medical records and the medico-administrative data was excellent, with a Kappa index of 0.985 (0.980-0.990). CONCLUSION: To reduce the rates of Caesarean sections, audits should be conducted on groups 1, 2 and 5 and local protocols developed. Simply by collecting the parity data, the excellent metrological quality of the medico-administrative data would allow systematisation of the Robson classification for each hospital.

[Can we reduce the decision-to-delivery interval in case of emergency cesarean sections by optimizing the premises' architecture?] / Peut-on diminuer le délai décision-extraction des césariennes en urgence en optimisant l'architecture des locaux ?

OBJECTIVE: To study the influence of architectural premises' improvements on decision-to-delivery interval (DDI) in case of emergency cesarean sections. METHODS: A retrospective observational Before-After study conducted in a type III maternity, first from 2004 to 2009 (Period 1, P1) then after moving our unit to new premises from 2009 to 2013 (P2). DDI, maternal and neonatal outcomes of every emergency cesarean section were studied. RESULTS: The mean DDI of extremely urgent cesarean significantly decreased from 21.3±10.3minutes during P1 (n=294) to 14.9±7.14minutes during P2 (n=165). During P2 there was an increase in the proportion of extreme emergency cesarean sections done in less than 30minutes (85.1% versus 93.5%, P=0.003) as according to the ACOG recommendations, and also an increase of DDI of less than 15minutes (25.8% versus 61.1%, P<0.001). Also during P2 if there was a reduction of umbilical cord pHs, which were correlated to DDI, we observed a reduction of neonatal hospitalizations (42.2% versus 35.7%, P<0.001). Apgar score was correlated to umbilical cord pH and birth weight, but not to DDI. CONCLUSION: The space optimization has allowed our level III maternity to improve the rate of extreme emergency cesarean sections performed with DDI of less than 30 and even 15minutes, according to international recommendations. These results were obtained by reducing the transfer time to the operating room. Despite a positive correlation between DDI and umbilical cord pH, there was an improvement in neonatal outcomes associated with a decrease of neonatal hospitalizations.

[Wegener's granulomatosis with anti-MPO c-ANCA revealed by uveitis]. / Maladie de Wegener à c-ANCA de type anti-MPO révélée par une uvéite.

Wegener's granulomatosis (WG) is a rare systemic necrotizing granulomatous vasculitis affecting small- to medium-sized vessels, associated with antineutrophil cytoplasm antibodies (ANCA), mainly anti-proteinase 3. Rarely, ANCA may be directed against myeloperoxidase. We report a 58-year-old woman who developed an uveitis as the presenting manifestation of Wegener's granulomatosis who highlight the usefulness of internist and ophthalmologist collaboration.

Stage sensitivity of Plasmodium vinckei petteri to quinine, mefloquine, and pyrimethamine.

The stage-dependent sensitivity of Plasmodium vinckei petteri to the antimalarial drugs quinine, mefloquine, and pyrimethamine was investigated using single subcurative doses and 2 different tests: a prepatency test evidencing the extension of the prepatent period according to the stage at which the drug was administered, and a patency test showing the morphological alterations of the parasites and the modifications of the parasitic pattern following drug treatment. Quinine activity was maximal when it hit the midterm trophozoite. No pigment clumping was seen and parasites developed normally until they reached the schizogonic stage when they became morphologically altered and unproductive. Mefloquine also acted on the midterm trophozoites. Parasites at this stage were killed immediately by the drug as evidenced by their degenerative appearance, and dead parasites lingered in the blood smears for at least 6 hr. However, although mefloquine was active during at least 48 hr (2 cycles), some trophozoites escaped destruction. The schizont stage was found to be the most sensitive to pyrimethamine, as previously reported for other parasite species. These results add to our previous reports showing that each drug acts preferentially on a specific stage of parasite development.

The chemosensitivity of the rodent malarias--relationships with the biology of merozoites.

According to the hypothesis proposed by Landau, Cambie & Chabaud (1990, Annalees de Parasitologie Humaine et Comparée 65: 101-103), the chemoresistance of malaria is related to the selection of strains with latent merozoites, the latter being capable of penetrating into red blood cells at other times than that of the time of schizogony and reinfect the host with as much of a delay as several days. They determine an asynchronism of the schizogonic rhythm and, being so far resistant to all known medication, should induce, at least to some extent, a chemoresistance. Consequently, there are three factors linked to merozoites: latency, asynchronism and chemoresistance. The relationship between asynchronism and latency of merozoites has been demonstrated previously (Cambie, Landau & Chabaud, 1990, Compte Rendus de l'Academie des Sciences de Paris 310: 183-188.). In the present work it was shown that the two classifications of strains, first in order of increasing chloroquine resistance, second in order of increasing degree of persistance of merozoites in the blood, are almost identical for the 10 strains, subspecies or species of Plasmodium considered. The relationship between latency of merozoites and chemoresistance appears to have been demonstrated.

Plasmodium yoelii nigeriensis: biological mechanisms of resistance to chloroquine.

The sensitivity to chloroquine according to the degree of synchronicity of Plasmodium yoelii nigeriensis, which is considered to be the most resistant of the rodent malaria strains, was studied. The infection was synchronised by means of a Percoll-glucose gradient which separates rings and young trophozoites from other stages. The mid-term trophozoite, when it predominated in the blood at the time of treatment, was shown to be as sensitive to chloroquine as Plasmodium vinckei petteri. According to previous results indicating that part of the population of merozoites is latent and penetrates around midnight, the inoculations were timed in order to obtain a lower or higher degree of synchronisation. The infection appeared to be better synchronised if rings and young trophozoites, were inoculated at 06:00 hrs rather than at 15:00 hrs and consequently the efficacy of chloroquine was higher in the former than in the latter.

3'-Phosphoadenosine 5'-phosphosulfate biosynthesis and the sulfation of cholecystokinin by the tyrosylprotein-sulfotransferase in rat brain tissue.

This article resumes the work we have accomplished in the past few years. Cholecystokinin sulfation is an important post-translational modification necessary for the biological activity of this peptide hormone. The tyrosyl protein sulfotransferase (TPST) activity from rat cerebral cortex was characterized. TPST activity is most probably responsible for the endogenous sulfation of CCK. TPST reaction kinetic properties were studied using radiolabeled 3'-phosphoadenosine 5'-phosphosulfate (PAPS) and the non-sulfated peptide acceptor terbutyloxycarbonyl-cholecystokinin octapeptide (BocCCK-8(ns)) as substrates, and brain microsomes as the enzyme source. The BocCCK-8 sulfating reaction data is consistent with the idea that TPST forward reaction follows an ordered Bi Bi mechanism. PAPS biosynthesis and availability was studied in slices from rat cerebral cortex incubated in the presence of [35S]sulfate. There is a rapid and dynamic turnover of the steady-state level of PAPS in brain cells which is decreased by depolarizing agents such as potassium, veratridine and glutamate. Furthermore, the presence of a membrane-bound PAPS biosynthesis inhibitor was observed. These results are discussed in view of the biological importance that the cell sulfating pathways might play in nerve cell activity.

Chronobiology and chronotherapy of malaria: investigations with murine malaria models.

The schizogonic rhythm of rodent malarias in the blood of mice varies from one species or subspecies to the other. Synchronous strains enable a precise study of the sensitive stage of the parasite to antimalarial drugs. Asynchronous strains are less sensitive than synchronous strains because of the delayed penetration of merozoites into red blood cells.

[Schizogony of Plasmodium yoelii nigeriensis. Role of latent merozoites]. / Schizogonie de Plasmodium yoelii nigeriensis. Rôle des mérozoïtes latents.

Several procedures were employed to try to specify the schizogonic cycle of Plasmodium yoelii nigeriensis. The Percoll-glucose gradient technique for concentrating the very young stages (rings and young trophozoites), allowing a very precise follow up of the development of the parasitaemia during the first schizogonic cycles. A method for studying the prepatencies, providing an approximation of the number of merozoites inoculated. A comparison between the numbers of merozoites present in the blood, after--firstly simple dilutions in saline, revealing the total number of merozoites,--secondly dilutions in saline after a passage of a few hours in the organism of a mouse, revealing the number of latent merozoites. It was shown that the infection, during the first two cycles, varies according to the time of inoculation. In all cases the increase of the parasitaemia occurred mainly from 00:01 to 06:00. This increase of parasitaemia in mice inoculated with the Percoll concentrated parasites was significantly high during the first cycle in mice inoculated at 06:00 and 09:00 and during the second cycle in those inoculated at 12:00, 15:00 and 18:00. However, differences were rapidly compensated and parasitaemias became comparable at the 3rd or 4th cycle when they ceased to be dependent on the time of inoculation.

Plasmodium vinckei petteri: identification of the stages sensitive to arteether.

Antimalarial activity of arteether, a derivative of artemisinin (qinghaosu) against blood-induced infections of the highly synchronous Plasmodium vinckei petteri rodent species of malaria was evaluated in Swiss mice. A single subcurative dose of arteether of 2.2 mg/kg body weight was injected subcutaneously to mice, either during the prepatent period or during the patent infection, when different stages of the parasitic cycle were present in the blood. It was shown that rings and young trophozoites were the most susceptible stages to arteether. The drug had no effect on merozoites and little effect on mid-term trophozoites which is the stage most sensitive to chloroquine. The alcoholic solution (10% alcohol in sterile water) had an immediate effect while the oily solution (miglyol 840) was active between 3 and 21 hr after injection.

Chronotherapy of malaria: identification of drug-sensitive stage of parasite and timing of drug delivery for improved therapy.

The cyclic nature of malarial fever in conjunction with the pharmacokinetic characteristics of antimalarial drugs, call for the conception of a chrono-therapeutic approach for the treatment of the disease. An experimental murine malarial model was devised using the highly synchronous species Plasmodium vinckei petteri to test this rationale. Sub-curative doses of chloroquine were injected sub-cutaneously to mice either during the prepatent period or during patent infection. Inspection of the effect of drug applied at different stages of the parasitic cycle, revealed that medium size trophozoites (MT) were the most susceptible stage to chloroquine, while ring and young trophozoite stages were refractory to the drug. Chloroquine given during these latter stages, affected the parasites when they developed into the MT stage. Drug treatment during the MT stage phase-shifted the schizogonic cycle by 18 hours. Hence, treatment with two consecutive injections given 18 hours apart, i.e. timed to the overwhelming presence of the MT stage in the circulation, gave the best therapeutic results.

Modulation of histamine release in the rat brain by kappa-opioid receptors.

The opioid modulation of histamine release was studied in rat brain slices labeled with L-[3H]histidine. The K(+)-induced [3H]histamine release from cortical slices was progressively inhibited by the preferential kappa-agonists ketocyclazocine, dynorphin A (1-13), Cambridge 20, spiradoline, U50,488H, and U69,593 in increasing concentrations. In contrast, the mu-agonists morphine, morphiceptin, and Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAGO) were ineffective as were the preferential delta-agonists [D-Ala2,D-Leu5]enkephalin (DA-DLE) and [D-Pen2,D-Pen5]enkephalin (DPDPE). Nor-binaltorphimine (nor-BNI) and MR 2266, two preferential kappa-antagonists, reversed the inhibitory effect of the various kappa-agonists more potently than did naloxone, with mean Ki values of 4 nM and 25 nM, respectively. The effects of ketocyclazocine and naloxone also were seen in slices of rat striatum, another brain region known to contain histaminergic nerve endings. We conclude that kappa-opioid receptors, presumably located on histaminergic axons, control histamine release in the brain. However, nor-BNI and naloxone failed, when added alone, to enhance significantly [3H]histamine release from cerebral cortex or striatum, and bestatin, an aminopeptidase inhibitor, failed to decrease K(+)-evoked [3H]histamine release. These two findings suggest that under basal conditions these kappa-opioid receptors are not tonically activated by endogenous dynorphin peptides. The inhibition of cerebral histamine release by kappa-agonists may mediate the sedative actions of these agents in vivo.

Modulation of histamine release and synthesis in the brain mediated by alpha 2-adrenoceptors.

The adrenergic regulation of histamine release was studied in rat brain slices labeled with L-[3H]histidine. Noradrenaline in increasing concentrations progressively inhibited K+-evoked [3H]histamine release from cortical slices, whereas phenylephrine and isoprenaline were ineffective. Yohimbine, a preferential alpha 2-adrenoceptor antagonist, reversed the noradrenaline effect in an apparently competitive manner and with a mean Ki value of 30 nM. Phentolamine reversed the noradrenaline effect with a similar potency, whereas propranolol was ineffective. The imidazolines clonidine and oxymetazoline acted as partial agonists, oxymetazoline even behaving as an apparent antagonist. In vivo clonidine also inhibited [3H]histamine formation in cerebral cortex, an effect reversed by the administration of yohimbine. However, yohimbine failed to increase significantly [3H]histamine release in vitro and [3H]histamine formation in vivo, suggesting that adrenergic receptors are not activated by endogenous noradrenaline released under basal conditions. It is concluded that adrenergic alpha 2-adrenoceptors presumably located on histaminergic axons control release and synthesis of histamine in the brain.

Regulation of histamine release and synthesis in the brain by muscarinic receptors.

The cholinergic modulation of histamine release and synthesis was studied in rat brain slices or synaptosomes labeled with L-[3H]histidine. Carbachol in increasing concentrations progressively reduced the K+-induced [3H]histamine release from cortical slices. Pirenzepine, a preferential M1-receptor antagonist, reversed the carbachol effect in an apparently competitive manner and with Ki values of 1-6 X 10(-8) M. 11-[(2-[(Diethylamino)methyl]-1-piperidinyl)acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116), considered a preferential M2-receptor antagonist, reversed the carbachol effect with a mean Ki of approximately 2 X 10(-7) M. Oxotremorine behaved as a partial agonist in the modulation of histamine release. Neostigmine, an acetylcholinesterase inhibitor, inhibited the K+-induced release of [3H]histamine from cortical slices, and the effect was largely reversed by pirenzepine, an observation suggesting a modulation by endogenous acetylcholine. The effects of carbachol and pirenzepine were observed with slices of other brain regions known to contain histaminergic nerve terminals or perikarya, as well as with cortical synaptosomes. The two drugs also modified, in opposite directions, [3H]histamine formation in depolarized cortical slices. In vivo oxotremorine inhibited [3H]histamine formation in cerebral cortex, and this effect was reversed by scopolamine. When administered alone, scopolamine failed to enhance significantly the 3H- labeled amine formation, a finding suggesting that muscarinic receptors are not activated by endogenous acetylcholine released under basal conditions. It is concluded that muscarinic heteroreceptors, directly located on histaminergic nerve terminals, control release and synthesis of histamine in the brain. These receptors apparently belong to the broad M1-receptor category and may correspond to a receptor subclass displaying a rather high affinity for AF-DX 116.

Formation and utilization of the active sulfate donor [35S]3'-phosphoadenosine 5'-phosphosulfate in brain slices: effects of depolarizing agents.

The accumulation and utilization of [35S]3'-phosphoadenosine 5'-phosphosulfate (PAPS) were studied in slices from rat cerebral cortex incubated in the presence of inorganic [35S]sulfate. [35S]PAPS levels were directly evaluated after either isolation by ion-exchange chromatography or quantitative enzymatic transfer of its active [35S]sulfate group to an acceptor phenol under the action of added phenolsulfotransferase activity. [35S]PAPS formation was also indirectly followed by incubating slices in the presence of beta-naphthol and measuring the levels of [35S]beta-naphthyl sulfate ([35S]beta-NS). Whereas [35S]PAPS levels rapidly reached a plateau, [35S]beta-NS formation proceeded linearly with time for at least 1 h, an observation indicating that the nucleotide was continuously synthesized and utilized for endogenous sulfation reactions. [35S]PAPS formation in slices was completely and rather potently blocked by 2,6-dichloro-4-nitrophenol (IC50 = 10 microM), an inhibitor of the PAPS-synthesizing enzyme system in a cytosolic preparation. [35S]PAPS accumulation and [35S]beta-NS formation were strongly reduced by depolarizing agents such as potassium or veratridine. At millimolar concentrations, various excitatory amino acids (glutamate, aspartate, cysteate, quisqualate, and homocysteate) also elicited similar effects, whereas kainate and N-methyl-D-aspartate were inactive. This suggests that PAPS synthesis is turned off when cerebral cells are strongly depolarized.

Effects of discriminant and non-discriminant dopamine antagonists on in vivo accumulation of 3H-N-propyl-norapomorphine in mouse striatum and tuberculum olfactorium.

The in vivo accumulation of 3H-N-propyl norapomorphine in mouse striatum and tuberculum olfactorium and its inhibition by a series of classical neuroleptics and discriminant benzamide derivatives previously identified in behavioural and radioligand experiments has been studied. The ID50 values in the two brain areas did not significantly differ with any studied compound. In addition the regional distribution of a discriminant compound related to sulpiride and administered in tritiated form to rats was rather homogeneous. These data do not indicate a preferential accumulation of these compounds in limbic as opposed to striatal areas.

[Dialysis dementia. Electroencephalographic study of a case]. / Diálise-demência. Estude eletrencefalográfico de um caso.

A case of a 65 years-old black man with chronic renal failure, treated with chronic haemodialysis, in which a dialysis dementia syndrome developed is reported. In the initial phase the electroencephalogram had the typical burst of sharp and slow waves, waning with haloperidol and diazepam treatment. The withdrawal of this medication induced reappearance of the symptoms and EEG. abnormalities. As soon as the patient came back to the diazepine (potassium clorazepate), the mental symptoms subsided, but few weeks later he died of a cerebral haemorrhage. The electroencephalographic features are described and a brief comment about this disease is made.