148 research outputs found
Clinical case of child with myoclonicastaticepilepsy (Doose syndrome)
No full textA clinical survey of a child's behavior, who has had multiple episodes of flinches and falls from the age of 3, is presented. At the age of 3,5 began generalized tonic-clonic seizures and a status of myoclonic seizures. Patient was experiencing loss of speech, self-service skills and walking skills. EEG has revealed an epileptic status of slow-wave sleep. Based on the clinical electroencephalographic data, a child was diagnosed with Doose syndrome, or epilepsy with myoclonic-astatic seizures. Despite the difficulties in assigning the treatment, seizures have regressed and epileptic status of sleep was blocked, with only a slight lag in neuro-mental development.Представлено клиническое наблюдение ребенка, у которого в возрасте трех лет появились эпизоды вздрагиваний, падений. В 3,5 года появились генерализованные тонико-клонические судороги, статусное течение миоклонических приступов. У пациента наблюдалась утрата речевых навыков, навыков самообслуживания и ходьбы. При ЭЭГ-исследовании был выявлен эпилептический статус медпенноволнового сна. Основываясь на данных клинико-электроэнцефалографической картины, ребенку был выставлен диагноз синдром Дузе, или эпилепсия с миоклонически-астатическими приступами. Несмотря на трудности в подборе терапии, приступы регрессировали, блокировался эпилептический статус сна с исходом в легкое отставание в нейропсихическом развитии
Das 'italienische' Jülich : Grundzüge im Konzept Alessandro Pasqualinis für die Stadtanlage, die Zitadelle und das Residenzschloss
No full textA close look at fluorescence quenching of organic dyes by tryptophan
No full textDoose S, Neuweiler H, Sauer M. A close look at fluorescence quenching of organic dyes by tryptophan. CHEMPHYSCHEM. 2005;6(11):2277-2285.Understanding fluorescence quenching processes of organic dyes by biomolecular compounds is of fundamental importance for in-vitro and in-vivo fluorescence studies. It has been reported that the excited singlet state of some oxazine and rhodamine derivatives is efficiently and almost exclusively quenched by the amino acid tryptophan (Trp) and the DNA base guanine via photoinduced electron transfer (PET). We present a detailed analysis of the quenching interactions between the oxazine dye MR121 and Trp in aqueous buffer. Steady-state and time-resolved fluorescence spectroscopy, together with fluorescence correlation spectroscopy (FCS), reveal three contributing quenching mechanisms: 1) diffusion-limited dynamic quenching with a bimolecular quenching rate constant k(d) of 4.0 x 10(9) s(-1) M-1, 2) static quenching with a bimolecular association constant K-s of 61 M-1, and 3) a sphere-of-action contribution to static quenching described by an exponential factor with a quenching constant lambda of 22 M-1. The latter two are characterized as nonfluorescent complexes, formed with approximate to 30% efficiency upon encounter, that are stable for tens of nanoseconds. The measured binding energy of 2030 kJmol(-1) is consistent with previous estimates from molecular dynamics simulations that proposed stacked complexes due to hydrophobic forces. We further evaluate the influence of glycerol and denaturant (guanidine hydrochloride) on the formation and stability of quenched complexes. Comparative measurements performed with two other dyes, ATTO 655 and Rhodamine 6G show similar results and thus demonstrate the general applicability of utilizing PET between organic dyes and Trp for the study of conformational dynamics of biopolymers on sub-nanometer length and nanosecond time-scales
Analysis of topiramate and its metabolites in plasma and urine of healthy subjects and patients with epilepsy by use of a novel liquid chromatography-mass spectrometry assay.
No full textA novel liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for quantification of topiramate (TPM) and its metabolites 10-hydroxy topiramate (10-OH-TPM), 9-hydroxy topiramate (9-OH-TPM), and 4,5-O-desisopropylidene topiramate (4,5-diol-TPM) in plasma and urine. The method uses 0.5 mL of plasma or 1 mL of urine that is extracted with diethyl ether and analyzed by LC-MS. Positive ion mode detection enables tandem mass spectrometric (MS/MS) identification of the aforementioned four compounds. Calibration curves of TPM, 4,5-diol-TPM, 9-OH-TPM, and 10-OH-TPM in plasma and urine were prepared and validated over the concentration range of 0.625 to 40 microg/mL using TPM-d(12) as an internal standard. Calibration curves were linear over this concentration range for TPM and its metabolites. Accuracy and precision ranged in urine from 83% to 114% and 4% to 13% (%CV), respectively, and in plasma from 82% to 108% and 6% to 13%, respectively. The applicability of the assay was evaluated by analyzing plasma samples from a healthy subject who received a single oral dose of TPM (200 mg) and urine samples from 11 patients with epilepsy treated with TPM (daily dose between 100 to 600 mg) alone or with other antiepileptic drugs. Only TPM was detected and quantified in the plasma samples, and its concentration ranged between 0.7 and 4.3 microg/mL. The concentrations of TPM and 10-OH TPM were quantifiable in all urine samples and ranged from 20 to 300 microg/mL for TPM and from 1 to 50 microg/mL for 10-OH-TPM. The metabolites 4,5-diol-TPM and 9-OH-TPM were also detected in all urine samples, but their concentrations were quantifiable only in 4 patients. An unidentified peak in the chromatograms obtained from patients' urine was attributed to 2,3-O-desisopropylidene topiramate (2,3-diol-TPM). Due to a lack of reference material of 2,3-diol TPM and the similar MS/MS spectrum with 4,5-diol-TPM, the calibration curves of 4,5-diol-TPM were used for the quantification of its isomer 2,3-diol-TPM. Based on these determinations, the apparent 2,3-diol-TPM-to-TPM concentration ratio in patients' urine ranged from 0.05 to 0.51 and the 10-OH-TPM-to-TPM ratio ranged from 0.02 to 0.17. In conclusion, a novel LC-MS method for the assay of TPM and four of its metabolites in plasma and urine was developed. Its utilization for analysis of urine samples from patients with epilepsy showed that the method was suitable for analysis of TPM and its metabolites in clinical samples. Two quantitatively significant TPM metabolites (10-OH-TPM and 2,3-diol-TPM) and two quantitatively minor metabolites (9-OH-TPM and 4,5-diol-TPM) were detected and quantified in urine samples from patients with epilepsy
MINCR is not a MYC-induced lncRNA (Letter)
No full textWe would like to offer two critical comments on the PNAS paper by Doose et al. entitled “MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells”No Full Tex
A COMPARATIVE STUDY OF THE EFFECT OF CARBAMAZEPINE AND VALPROIC ACID ON THE PHARMACOKINETICS AND METABOLIC PROFILE OF TOPIRAMATE AT STEADY STATE IN PATIENTS WITH EPILEPSY
No full textPURPOSE: To compare the influence of enzyme-inducing comedication and valproic acid (VPA) on topiramate (TPM) pharmacokinetics and metabolism at steady state.
METHODS: Three groups were assessed: (a) patients receiving TPM mostly alone (control group, n =13); (b) patients receiving TPM with carbamazepine (CBZ; n = 13); and (c) patients receiving TPM with VPA (n = 12). TPM and its metabolites were assayed in plasma and urine by liquid chromatography-mass spectrometry (LC-MS).
RESULTS: No significant differences were found in TPM oral (CL/F) and renal (CL(r)) clearance between the VPA group and the control group. Mean TPM CL/F and CL(r) were higher in the CBZ group than in controls (2.1 vs. 1.2 L/h and 1.1 vs. 0.6L/h, respectively; p 0.05). Urinary recovery of 2,3-O-des-isopropylidene-TPM (2,3-diol-TPM) accounted for 3.5% of the
dose in controls, 2.2% in the VPA group (p > 0.05), and 13% in the CBZ group (p <0.05). The recovery of 10-hydroxy-TPM (10-OH-TPM) was twofold higher in the CBZ group than in controls, but it accounted for only <2% of the dose. The plasma concentrations of TPM metabolites were several fold lower than those of the parent drug.
CONCLUSIONS: Renal excretion remains a major route of TPM elimination, even in the presence of enzyme induction. The twofold increase in TPM-CL/F in patients taking CBZ can be ascribed, at least in part, to stimulation of the oxidative
pathways leading to formation of 2,3-diol-TPM and 10-OH-TPM. VPA was not found to have any clinically significant influence on TPM pharmacokinetic and metabolic profiles
Maschinelle Dokumentation von klinischen und EEG-Verlaufsbeobachtungen in einer Anfallsambulanz
No full textDie Verfasser berichten über ein System für die maschinelle Dokumentation von EEG- und klinischen Befunden bei Langzeitbeobachtungen von Epileptikern. Auf drei verschiedenen, durch spaltengleiche Verlochung von Kennzahlen aufeinander abgestimmten Karten (IBM, 80 Spalten) werden Vorgeschichte und Befunde, Verlaufsbeobachtungen (jahrweise zusammengefaßt) und EEG-Befunde verlocht. Außer durch maschinelle Sortierung können Verlaufsbeobachtungen durch Tabellen ausgewertet werden: Maschinelle Sortierung des Kartenmaterials nach der zeitlichen Folge der Befunderhebung und anschließende Tabellierung. Bei der Bearbeitung von speziellen Fragestellungen kann das System durch weitere Karten ergänzt bzw. durch maschinelle Zusammenziehung von bestimmten Sachverhalten auf einer neuen Karte modifiziert werden.</jats:p
Incremental Validation of Real-Time Systems
No full textInternational audienceReal-time embedded systems are used in highly important or even vital tasks (avionic and medical systems, etc.), thus having strict temporal constraints that need to be validated. Existing solutions use temporal logic, automata or scheduling techniques. However, scheduling techniques are often pessimistic and require an almost complete knowledge of the system, and formal methods can be ill-fitted to manipulate some of the concepts involved in real-time systems. In this article, we propose a method that has the advantages of formal methods and some simplicity in manipulating real-time systems notions. This method is able to model and validate all the classical features of real-time systems, without any pessimism, while guaranteeing the end of the validation process. Moreover, its formalism enables to validate systems of which we have only a partial knowledge, and thus to validate or invalidate a system still under design. This latest point is very important, since it greatly decreases the cost of design backtracks
Genotype-phenotype Correlation In Dravet Syndrome With Scn1a Mutation Increase Efficiency Of Molecular Diagnosis [correlações Entre O Genótipo E O Fenótipo Na Síndrome De Dravet Com Mutações Em Scn1a Aumentam A Acurácia Do Diagnóstico Molecular]
No full textObjectives: The purpose of this study was to advance the knowledge on the clinical use of SCN1A testing for severe epilepsies within the spectrum of generalized epilepsy with febrile seizures plus by performing genetic screening in patients with Dravet and Doose syndromes and establishing genotype-phenotype correlations. Methods: Mutation screening in SCN1A was performed in 15 patients with Dravet syndrome and 13 with Doose syndrome. Eight prediction algorithms were used to analyze the impact of the mutations in putative protein function. Furthermore, all SCN1A mutations previously published were compiled and analyzed. In addition, Multiplex Ligation-Dependent Probe Amplification (MLPA) technique was used to detect possible copy number variations within SCN1A. Results: Twelve mutations were identified in patients with Dravet syndrome, while patients with Doose syndrome showed no mutations. Our results show that the most common type of mutation found is missense, and that they are mostly located in the pore region and the N- and C-terminal of the protein. No copy number variants in SCN1A were identified in our cohort. Conclusions: SCN1A testing is clinically useful for patients with Dravet syndrome, but not for those with Doose syndrome, since both syndromes do not seem to share the same genetic basis. Our results indicate that indeed missense mutations can cause severe phenotypes depending on its location and the type of amino-acid substitution. Moreover, our strategy for predicting deleterious effect of mutations using multiple computation algorithms was efficient for most of the mutations identified.1826062Singh, R., Andermann, E., Whitehouse, W.P., Harvey, A.S., Keene, D.L., Seni, M.H., Crossland, K.M., Scheffer, I.E., Severe myoclonic epilepsy of infancy: Extended spectrum of GEFS+? (2001) Epilepsia, 42, pp. 837-844Escayg, A., Heils, A., Macdonald, B.T., Haug, K., Sander, T., Meisler, M.H., A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus and prevalence of variants in patients with epilepsy (2001) Am J Hum Genet, 68, pp. 866-873Wallace, R.H., Scheffer, I.E., Barnett, S., Richards, M., Dibbens, L., Desai, R.R., Lerman-Sagie, T., Berkovic, S.F., Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus (2001) Am J Hum Genet, 68, pp. 859-865Ottman, R., Hirose, S., Jain, S., Lerche, H., Lopes-Cendes, I., Noebels, J.L., Serratosa, J., Scheffer, I.E., Genetic testing in the epilepsies - Report of the ILAE Genetics Commission (2010) Epilepsia, 51 (4), pp. 655-670Klassen, T., Davis, C., Goldman, A., Burgess, D., Chen, T., Wheeler, D., McPherson, J., Noebels, J., Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy (2011) Cell, 145, pp. 1036-1048http://sift.bii.a-star.edu.sg/http://genetics.bwh.harvard.edu/pph/http://genetics.bwh.harvard.edu/pph2/http://mmb2.pcb.ub.es:8080/PMuthttp://mutpred.mutdb.orghttp://gpcr2.biocomp.unibo.it/cgi/predictors/PhD-SNP/PhD-SNP.cgihttp://rostlab.org/services/snaphttp://snps-and-go.biocomp.unibo.it/snps-and-goLossin, C., Rhodes, T.H., Desai, R.R., Vanoye, C.G., Wang, D., Carniciu, S., Devinsky, O., George Jr., A.L., Epilepsy-Associated Dysfunction in the Voltage-Gated Neuronal Sodium Channel SCN1A (2003) Journal of Neuroscience, 23 (36), pp. 11289-1129
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