Reduction of plasma alanine aminotransferase during vigabatrin treatment.

In 9 drug-resistant patients with partial seizures treated with vigabatrin, gamma-vinyl GABA (VGB), alanine aminotransaminase (ALAT) activity in plasma was significantly reduced. Comparison of in vitro with in vivo measurements led us to conclude that this reduction is mainly an in vivo phenomenon, perhaps due to cross-enzyme inhibition. The assessment of two biological variables linked with ALAT, glucose and alanine levels under fasting conditions, failed to show any significant metabolic alterations. VGB is an effective drug for partial epilepsy. Our observations do not suggest that reduced ALAT activity is of clinical concern.

A new, automated, four-colour interphase FISH approach for the simultaneous detection of specific aneuploidies of diagnostic and prognostic significance in high hyperdiploid ALL

In hyperdiploid acute lymphoblastic leukaemia (ALL), the simultaneous occurrence of specific aneuploidies confers a more favourable outcome than hyperdiploidy alone. Interphase (I) FISH complements conventional cytogenetics (CC) through its sensitivity and ability to detect chromosome aberrations in non-dividing cells. To overcome the limits of manual I-FISH, we developed an automated four-colour I-FISH approach and assessed its ability to detect concurrent aneuploidies in ALL. I-FISH was performed using centromeric probes for chromosomes 4, 6, 10 and 17. Parameters established for automatic nucleus selection and signal detection were evaluated (3 controls). Cut-off values were determined (10 controls, 1000 nuclei/case). Combinations of aneuploidies were considered relevant when each aneuploidy was individually significant. Results obtained in 10 ALL patients (1500 nuclei/patient) were compared with those by CC. Various combinations of aneuploidies were identified. All clones detected by CC were observed by I-FISH. I-FISH revealed numerous additional abnormal clones, ranging between 0.1% and 31.6%, based on the large number of nuclei evaluated. Four-colour automated I-FISH permits the identification of concurrent aneuploidies of prognostic significance in hyperdiploid ALL. Large numbers of cells can be analysed rapidly by this method. Owing to its high sensitivity, the method provides a powerful tool for the detection of small abnormal clones at diagnosis and during follow up. Compared to CC, it generates a more detailed cytogenetic picture, the biological and clinical significance of which merits further evaluation. Once optimised for a given set of probes, the system can be easily adapted for other probe combinations.

Genometric analyses of the organization of circular chromosomes: a universal pressure determines the direction of ribosomal RNA genes transcription relative to chromosome replication.

Selective pressures related to gene function and chromosomal architecture are acting on genome sequences and can be revealed, for instance, by appropriate genometric methods. Cumulative nucleotide skew analyses, i.e., GC, TA, and ORF orientation skews, predict the location of the origin of DNA replication for 88 out of 100 completely sequenced bacterial chromosomes. These methods appear fully reliable for proteobacteria, Gram-positives, and spirochetes as well as for euryarchaeotes. Based on this genome architecture information, coorientation analyses reveal that in prokaryotes, ribosomal RNA (rRNA) genes encoding the small and large ribosomal subunits are all transcribed in the same direction as DNA replication; that is, they are located along the leading strand. This result offers a simple and reliable method for circumscribing the region containing the origin of the DNA replication and reveals a strong selective pressure acting on the orientation of rRNA genes similar to the weaker one acting on the orientation of ORFs. Rate of coorientation of transfer RNA (tRNA) genes with DNA replication appears to be taxon-specific. Analyzing nucleotide biases such as GC and TA skews of genes and plotting one against the other reveals a taxonomic clusterization of species. All ribosomal RNA genes are enriched in Gs and depleted in Cs, the only so far known exception being the rRNA genes of deuterostomian mitochondria. However, this exception can be explained by the fact that in the chromosome of the human mitochondrion, the model of the deuterostomian organelle genome, DNA replication, and rRNA transcription proceed in opposite directions. A general rule is deduced from prokaryotic and mitochondrial genomes: ribosomal RNA genes that are transcribed in the same direction as the DNA replication are enriched in Gs, and those transcribed in the opposite direction are depleted in Gs.

Estimation of the viscoelastic properties of vessel walls using a computational model and Doppler ultrasound

Human arteries affected by atherosclerosis are characterized by altered wall viscoelastic properties. The possibility of noninvasively assessing arterial viscoelasticity in vivo would significantly contribute to the early diagnosis and prevention of this disease. This paper presents a noniterative technique to estimate the viscoelastic parameters of a vascular wall Zener model. The approach requires the simultaneous measurement of flow variations and wall displacements, which can be provided by suitable ultrasound Doppler instruments. Viscoelastic parameters are estimated by fitting the theoretical constitutive equations to the experimental measurements using an ARMA parameter approach. The accuracy and sensitivity of the proposed method are tested using reference data generated by numerical simulations of arterial pulsation in which the physiological conditions and the viscoelastic parameters of the model can be suitably varied. The estimated values quantitatively agree with the reference values, showing that the only parameter affected by changing the physiological conditions is viscosity, whose relative error was about 27% even when a poor signal-to-noise ratio is simulated. Finally, the feasibility of the method is illustrated through three measurements made at different flow regimes on a cylindrical vessel phantom, yielding a parameter mean estimation error of 25%.

@neurIST infrastructure for advanced disease management through integration of heterogeneous data, computing, and complex processing services

The increasing volume of data describing humandisease processes and the growing complexity of understanding, managing, and sharing such data presents a huge challenge for clinicians and medical researchers. This paper presents the@neurIST system, which provides an infrastructure for biomedical research while aiding clinical care, by bringing together heterogeneous data and complex processing and computing services. Although @neurIST targets the investigation and treatment of cerebral aneurysms, the system’s architecture is generic enough that it could be adapted to the treatment of other diseases.Innovations in @neurIST include confining the patient data pertaining to aneurysms inside a single environment that offers cliniciansthe tools to analyze and interpret patient data and make use of knowledge-based guidance in planning their treatment. Medicalresearchers gain access to a critical mass of aneurysm related data due to the system’s ability to federate distributed informationsources. A semantically mediated grid infrastructure ensures that both clinicians and researchers are able to seamlessly access andwork on data that is distributed across multiple sites in a secure way in addition to providing computing resources on demand forperforming computationally intensive simulations for treatment planning and research.

Topographical body fat distribution links to amino acid and lipid metabolism in healthy non-obese women.

Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25-45 y, BMI: 28-40 kg/m(2)) under healthy clinical conditions and monitored over a 2 weeks period we examined the relationships between different body composition parameters, estimates of visceral adiposity and blood/urine metabolic profiles. Metabonomics and lipidomics analysis of blood plasma and urine were employed in combination with in vivo quantitation of body composition and abdominal fat distribution using iDXA and computerized tomography. Of the various visceral fat estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant associations with regio-specific body lean and fat composition. The integration of these visceral fat estimates with metabolic profiles of blood and urine described a distinct amino acid, diacyl and ether phospholipid phenotype in women with higher visceral fat. Metabolites important in predicting visceral fat adiposity as assessed by Random forest analysis highlighted 7 most robust markers, including tyrosine, glutamine, PC-O 44∶6, PC-O 44∶4, PC-O 42∶4, PC-O 40∶4, and PC-O 40∶3 lipid species. Unexpectedly, the visceral fat associated inflammatory profiles were shown to be highly influenced by inter-days and between-subject variations. Nevertheless, the visceral fat associated amino acid and lipid signature is proposed to be further validated for future patient stratification and cardiometabolic health diagnostics.

Missale ad usum ecclesiae Parisiensis .

Cf. notice du ms. par Leroquais, Sacramentaires, II, 180-183 n° 366. Les incipit des proses ont été relevés dans la table des incipit. F. 1-6v Calendrier de Paris : 3 janv., en rouge, «Genovefe virg. IX lc.» (1); 22 avr., «Inventio corporis s. Dyonisii sociorumque ejus. Oportune virg. semid.» (2v); 28 mai, en rouge, «Germani ep. Parisiensis semid. Carauni mart. memoria» (3); 25juin, en violet, «Translatio s. Eligii ep.» (3v); en violet, «In prima dominica hujus mensis [augusti] fit d. de cruce» [réception à Notre-Dame d'un fragment de la vraie Croix] (4v); 9 oct., en rouge, «Dyonisii sociorumque ejus duplex» (5v); 28 oct., «Germani ep. Translatio s. Genovefe virg. mart. memoria» (5v); 3 nov. «Marcelli ep. Parisiensis dupl.»; 13 nov., «Gendulphi ep. et conf. [Parisiensis] dupl.»; 26 nov., en violet, «Genovefe virg. de miraculo [ardentium] IX lc.» (6); 4 déc., «Susceptio capillorum b. Marie et capitis b. Dyonisii in ecclesia Parisiensi» (6v). Le calendrier ne contient pas la fête de s. Louis au 25 août (établie en 1298) ni au 17 mai la translation du chef de s. Louis à la Sainte-Chapelle (en 1306); — Ajout du XIVe s. au 30 avr., «Eutropii mart. et conf.» [culte établi à Paris en 1296] (2v); cf. Leroquais, Bréviaires, I, CXII-CXIII, Tableau chronologique des fêtes parisiennes. — Au début de chaque mois, vers sur les jours égyptiaques (éd. Hennig, Traditio, XI (1955), 84 III), sauf celui de janvier (1) qui correspond au premier vers de la série éd. par Riese (Anthol. lat., I2 (1906), 680a); — À la fin de février, vers sur l'année bissextile : «Byssextum sexte martis tenuere kalende...»; cf. ms. Latin 3162, f. 102 (1v); — À la fin de mars, vers sur la date de Pâques : «Post martis nonas ubi sit nova luna requiras...» (2); — Notations astrologiques et de comput, passim. F. 7-353v Temporal, avec parties chantées notées. Incomplet du début par la perte du premier f., il commence dans la prose du premier dimanche de l'Avent : «... [eterna indefici]ens mundi vita...» (7). À remarquer : «dominica IIIa [in Adventu] more ecclesie Parisiensis» (24v); — Cérémonie des Cendres avec rubriques liturgiques (62v-66v); — Dimanche des Rameaux, «congregatis processionibus conventualibus in ecclesia B. Marie, capiceriis portantibus capsam et tribus clericis in albis paratis tres textus, exitur de ecclesia nichil cantando et sic eundum est ad ecclesiam Sancte Genovefe de Monte...» (147); cf. Leroquais, 181; — Dans l'évangile des Rameaux, le Christ est désigné par la lettre L, le narrateur par la lettre C et les autres par la lettre S (153-158); dans les autres évangiles de la Passion (162-186 passim), ces lettres suscrites ont été effacées et remplacées à la mine de plomb de façon sporadique, le Christ étant alors désigné par une croix; — «Oremus pro papa nostro N...» (186v); «... pro christianissimo rege nostro N...» (187); — Parmi les litanies, «s.Stephane... s. Dyonisi...» (191v)..., « s. Lucane... s. Justine... s. Gendulphe... s. Germane...» (199)..., « s. Genovefa...» (201v). — «Incipit ordo misse. Sacerdos primo induat se rocheto dicens : Actiones nostras...» (203v-206); pour les rubriques liturgiques, cf. Leroquais, 181; — Préfaces notées : «Incipiunt prefationes...» (206-210); — Canon de la messe (210-213); pour les rubriques liturgiques, cf. Leroquais, 182; — «In die Re[sur]rectionis» (214); — «In die sancto [Pentecostes]» (262v); — [De sancta Trinitate] (280v); — «Dominica XXVa» (348v); — «In dedicatione ecclesie» (350-353v). La fête du Saint-Sacrement ne figure pas. F. 354-496v Sanctoral, avec parties chantées notées. À noter parmi les saints parisiens : 3 janv., «S. Genovefe virg.» (373v); 22 avr., «Inventio corporis s. Dyonisii, Rustici et Eleuterii» (398v); — 28 mai, «S. Germani ep. Parisiensis» (407v); — 10 juin, «S. Landerici Parisiensis ep.» (410); — 26 juill., «In translatione s. Marcelli» (432); — 11août, «De receptione s. corone...» (443v); —, 4 oct., «Auree virg. [abb. Parisiis]» (480); 9 oct., «In die [s. Dyonisii]», avec octave (481v); — 28oct., «In translatione s. Genovefe» (487); — 3nov., «S. Marcelli Parisiensis ep.», avec octave (489v); — 26 nov., «S. Genovefe de miraculo ardentium» (495); — «De s. Gendulpho. Prosa» (495). F. 497-541 Commun des saints, avec pièces chantées notées. F. 541-559 Messes votives, sans parties notées à l'exception de la messe des morts (551v-556). Aux ff. 546v-547, en marge de la messe «pro amico», deux additions d'une écriture cursive de la fin du XIVe s. précisent : «ducem nostrum et duxissem ejusque prolem». — Prières diverses (556-559). F. 559-563 Rituel de mariage. «Incipit ordo ad sponsam benedicendam. Cum venerint ante valvas ecclesie sponsus et sponsa, accinctus sacerdos alba et stola... auxilium et argentum super scutum positum benedicat dicens : Manda Deus... Tunc aspergatur aqua benedicta et thurificetur et sponsus et sponsa; quo facto sacerdos dicat : Bones genz nos avons faiz les bans III foiz de ces II genz et encore les faison nous, que se il i a nul ne nule qui sache enpeschement par quoi l'un ne puisse avoir l'autre par loi de mariage, si le die. Et re[spon]dent assistentes : Nous ni savons se bien non. Quo audito, accipiat sacerdos manum dexteram sponse et ponat in dextera manu sponsi et dicat... nominandos eos : Vos Marie et vos Jeham vous prometez, fianciez et jurez l'un à l'autre à garder la foi et la loiauté du mariage... Tunc sacerdos tradat anulum sponso et sponsus autem per manum sacerdotis primo in police sponse... dicens... : Marie de cest annel t'espous et de mon cors t'ennor et de douaire qui est devisiez entre mes amis et les tiens. In nomine... Secundo in indice dicens... Tercio in medio dicens : Et Spiritus sancti. Amen... Postea sacerdos extensa manu super illos dicat orationes... Tunc sacerdos centus [sic] sponsum per manum dexteram et sponsam et introducat eos in ecclesiam...» (559-559bis); — Messe de mariage, comportant deux préfaces notées : «Deinde celebratur missa...» (559bis-562v); pour les rubriques liturgiques, cf. Leroquais, 183. — «Missa celebrata, recedant sponsus et sponsa et, ipsis stantibus ante hostium domus illorum presentibus pane et vinum [sic], faciat sacerdos benedictionem super panem dicens : Benedic Domine creaturam... Tunc sponsus mordet in pane, postea sponsa. Item benedictio super vinum... Tunc sponsus bibat, postea sponsa. Quo facto introducit eos sacerdos per manum in domum... Item in sero benedictio thalami... Tunc turificet thalamum, postea sponsum et sponsam sedentes vel jacentes in lecto suo benedicat dicens : Benedic Domine adulescentulos...» (562v-563) (éd. avec variantes par E. Martène, De antiquis Ecclesiae ritibus, II, 374-376, d'après le ms. Latin 859A); même ordo dans le ms. NAL 2649, f. 333-336. F. 563-565v Exorcisme de l'eau et du sel (563-564v). — «Pro Terra sancta» (564v-565). — «Pro rege nostro» (565). — «Benedictio pere et baculi peregrinorum» (565-565v). — «Benedictio crucis... Benedictio novorum fructuum... Benedictio panis» (565v).

Extraits de CHRONIQUES, et en particulier de textes relatifs à la NORMANDIE.

Contient : Extrait des Annales S. Dionysii ad cyclos paschales [cf. E. Berger, dans Bibl. de l'Ecole des chartes, t. XL, p. 270] ; Extrait de la chronologie des rois de France, de Bernard Gui, d'après un ms. de Petau, communiqué par Camuzat ; Fragment sur Philippe le Bel, par un moine de Saint-Denis (Frère Ives) [cf. Molinier, Sources, n° 2847] ; Extrait du Chronicon Colmariense [Mon. Germ., SS., t. XVII, p. 240] ; Lettre de Philippe IV relative à la bataille de Mons-en-Pévèle, septembre 1304 ; Fragment (1285-1343) de la chronique de l'Anonyme de Caen [Molinier, n° 1163] ; Extraits historiques relatifs aux fils de Philippe le Bel ; Chartes de Guillaume le Conquérant et d'Henri Ier pour l'abbaye de Montebourg ; Notice de la fondation de ladite abbaye ; Gesta abbatum Fontanellensium, rédaction abrégée. Incipit : « Wandregisilus qui et Wando... » [cf. Archiv, VIII, 373] ; Gesta abbatum Fontanellensium, précédés de la Commemoratio Ansberti [cf. éd. Loewenfeld, Hanovre, 1888, in-8°, et D'Achery, Spicil., éd. in-fol., t. II, p. 263] ; Chartes de l'abbaye de Saint-Wandrille (1024-1177) et extraits de pièces des XIIIe et XIVe siècles relatives à la même abbaye ; Extraits de la chronique de Robert de Thorigny, d'après un ms. du Mont-Saint-Michel ; Extraits d'Annales de Rouen, d'après un ms. de Bigot [ms. lat. 5530 ; cf. L. Delisle, dans Hist. littér., t. XXXII, p. 196] ; Chronologia urbis Rothomagensis (94-1549), composée par M. de La Mare ; Chron. Nortmannorum [cf. Duchesne, Rer. Franc. scriptores, t. II, p. 524, et L. Delisle, dans Notices et extraits, t. XXXVIII, p. 697] ; Annales de Saint-Wandrille, dites Chronicon Thosanum, [cf. Hist. littér., t. XXXII, p. 204] ; Eloge en vers de Lanfranc [Mabillon, AA. SS. Ben., t. VI, II, p. 659], d'après un ms. de Saint-Florent-lès-Saumur ; Trêve de Dieu pour la Normandie, du temps de Gullaume le Conquérant ; Extrait d'un ms. intitulé « Cursus Normanniae », communiqué par J. Sirmond ; Notice sur les abbés de Fécamp, jusqu'à Henri de Lorraine (1613-1642), d'après un ms. de M. de la Meschinière ; Catalogue des abbés du même monastère jusqu'à François de Joyeuse (1600-1613) ; Extraits d'un cartulaire de Saint-Michel du Tréport ; Extraits d'un calendrier de la même abbaye ; Extraits de la vie de saint Exupère, évêque de Bayeux ; Vers sur l'abbaye de Jumièges, attribués au moine Adrien (cf. Frère, Bibliogr. normand, t. I, p. 154) ; Extraits d'un calendrier des chanoines d'Eu ; Liste des évêques de Lisieux jusqu'à Guillaume Du Vair (1618-1621) ; Evêques de Bayeux jusqu'à Jacques d'Angennes (1606-1647) ; Evêques de Coutances jusqu'à Nicolas de Briroi (1589-1620) ; Evêques d'Evreux jusqu'à François de Péricard (1613-1646) ; Notes sur les chartes de l'abbaye de Savigny ; Chartes du Breuil-Benoît ; Catalogue des abbés de Jumièges ; Fondation de l'abbaye de Blanchelande (1154), et extraits des chartes de ce monastère ; Notes sur le fouage à lever en Normandie et sur les forteresses occupées par le roi, d'après les registres du Trésor des chartes ; Extraits des archives de Notre-Dame d'Ardenne ; Extraits des archives de Saint-Etienne de Caen ; Chartes diverses relatives à la Normandie (1217-1262) ; Annales d'Avranches, 837-1359 [cf. Hist. de Fr., t. XXIII, p. 568] ; Extraits de deux rédactions de la Vita Vanengi [Bibl. hag. lat., 8811 et 8813] ; Traité entre Abu-Issac et Vibaldus, envoyé de l'empereur Frédéric II (1231), traduction latine par M. Obelius Cicero [Mon. Germ., Const., t. II, p. 187] ; Extraits de chroniques arabes relatifs à l'histoire de Sicile, traduits par le même

Maternal side-effects after multiple courses of antenatal corticosteroids (MACS): the three-month follow-up of women in the randomized controlled trial of MACS for preterm birth study.

OBJECTIVE: A single course of antenatal corticosteroids (ACS) is associated with a reduction in respiratory distress syndrome and neonatal death. Multiple Courses of Antenatal Corticosteroids Study (MACS), a study involving 1858 women, was a multicentre randomized placebo-controlled trial of multiple courses of ACS, given every 14 days until 33+6 weeks or birth, whichever came first. The primary outcome of the study, a composite of neonatal mortality and morbidity, was similar for the multiple ACS and placebo groups (12.9% vs. 12.5%), but infants exposed to multiple courses of ACS weighed less, were shorter, and had smaller head circumferences. Thus for women who remain at increased risk of preterm birth, multiple courses of ACS (every 14 days) are not recommended. Chronic use of corticosteroids is associated with numerous side effects including weight gain and depression. The aim of this postpartum assessment was to ascertain if multiple courses of ACS were associated with maternal side effects. METHODS: Three months postpartum, women who participated in MACS were asked to complete a structured questionnaire that asked about maternal side effects of corticosteroid use during MACS and included the Edinburgh Postnatal Depression Scale. Women were also asked to evaluate their study participation. RESULTS: Of the 1858 women randomized, 1712 (92.1%) completed the postpartum questionnaire. There were no significant differences in the risk of maternal side effects between the two groups. Large numbers of women met the criteria for postpartum depression (14.1% in the ACS vs. 16.0% in the placebo group). Most women (94.1%) responded that they would participate in the trial again. CONCLUSION: In pregnancy, corticosteroids are given to women for fetal lung maturation and for the treatment of various maternal diseases. In this international multicentre randomized controlled trial, multiple courses of ACS (every 14 days) were not associated with maternal side effects, and the majority of women responded that they would participate in such a study again.

Genometrics as an essential tool for the assembly of whole genome sequences: the example of the chromosome of Bifidobacterium longum NCC2705.

BACKGROUND: Analysis of the first reported complete genome sequence of Bifidobacterium longum NCC2705, an actinobacterium colonizing the gastrointestinal tract, uncovered its proteomic relatedness to Streptomyces coelicolor and Mycobacterium tuberculosis. However, a rapid scrutiny by genometric methods revealed a genome organization totally different from all so far sequenced high-GC Gram-positive chromosomes. RESULTS: Generally, the cumulative GC- and ORF orientation skew curves of prokaryotic genomes consist of two linear segments of opposite slope: the minimum and the maximum of the curves correspond to the origin and the terminus of chromosome replication, respectively. However, analyses of the B. longum NCC2705 chromosome yielded six, instead of two, linear segments, while its dnaA locus, usually associated with the origin of replication, was not located at the minimum of the curves. Furthermore, the coorientation of gene transcription with replication was very low. Comparison with closely related actinobacteria strongly suggested that the chromosome of B. longum was misassembled, and the identification of two pairs of relatively long homologous DNA sequences offers the possibility for an alternative genome assembly proposed here below. By genometric criteria, this configuration displays all of the characters common to bacteria, in particular to related high-GC Gram-positives. In addition, it is compatible with the partially sequenced genome of DJO10A B. longum strain. Recently, a corrected sequence of B. longum NCC2705, with a configuration similar to the one proposed here below, has been deposited in GenBank, confirming our predictions. CONCLUSION: Genometric analyses, in conjunction with standard bioinformatic tools and knowledge of bacterial chromosome architecture, represent fast and straightforward methods for the evaluation of chromosome assembly.