Multi-elemental Nd, Sm, Eu, Gd isotope ratio measurements by stop-flow isotachophoresis coupled to MC-ICPMS.

In this study, a new analytical procedure based on isotachophoresis (ITP) coupled to a multi collector inductively coupled plasma mass spectrometer named Stop-Flow-ITP-MC-ICPMS is developed for exhaustive and high-precision multi-elemental isotopic characterization. We demonstrate that Stop-Flow-ITP makes it possible to stop the analytes migration several times for a duration compatible with the detector configuration changes without losing the separation performance. With this procedure, isotope ratio measurements of four lanthanides of interest for nuclear applications (Nd, Sm, Eu and Gd) were obtained with a reproducibility better than 0.4% in a single analysis with only 20ng of each element. A nebulization interface between ITP and MC-ICPMS composed of a dual inlet spray chamber and a multiple flow stream valve made it possible to perform isotopic reference standard injections for on-line mass bias correction by the sample standard bracketing approach. The flexibility of the Stop-Flow-ITP-MC-ICPMS procedure opens the way to online determination of isotope ratio measurements of multiple analytes present in a sample in a single analysis.

Evaluation of superficially and fully porous particles for HILIC separation of lanthanide-polyaminocarboxylic species and simultaneous coupling to ESIMS and ICPMS.

In this work, amide-bonded columns packed with fully porous particles (FPP) and superficially porous particles (SPP) were evaluated to separate lanthanide-polyaminocarboxylic species by hydrophilic interaction liquid chromatography (HILIC), using two model samples of interest in nuclear and other industrial applications. We assessed the gains achieved by reducing the dimensions of the columns along with the size of the FPPs to sub-2 µm and by using sub-3 µm SPP-packed columns. The FPP-packed Acquity column (100 × 2.1 mm; 1.7 µm) performed better than the SPP-packed Accucore column (150 × 2.1 mm; 2.6 µm), with a separation that was two times more efficient and three times shorter, while generating around 30% less in effluent volumes. This column was also coupled simultaneously to electrospray ionisation mass spectrometry (ESIMS) and inductively coupled plasma mass spectrometry (ICPMS). The instrumental set-up was performed in a conventional laboratory, by taking into account the geometrical constraints existing in the laboratory dedicated to radioelement analysis. Furthermore, separation of the series of lanthanide (Ln) species was demonstrated for the first time thanks to the separation mode of hydrophilic interaction liquid chromatography.

Follow-up study of patients treated with olanzapine pamoate in France in real-life treatment situation.

OBJECTIVE: To characterize patients treated with olanzapine pamoate in French centers and investigate the conditions of use of olanzapine pamoate in real-life treatment situation. METHODS: Data came from French sites participating in an international post-authorization safety study. In this observational study, patients diagnosed with schizophrenia were receiving commercially available olanzapine pamoate, in accordance with their physician's usual standard of care. Data were collected during routine visits within the standard course of patient care. RESULTS: One hundred and thirty eight patients (male, 73.9%; mean age, 39.4 years; mean duration of disease, 12.7years) received olanzapine pamoate and were included in the study by 32 investigative psychiatrists distributed across 20 different sites (psychiatric hospitals). During the period of analysis, a total of 2975 injections of olanzapine pamoate was administered to the patients. The mean duration of olanzapine pamoate exposure was 475 days (1.3years). During follow-up, 13.8% of all patients had at least one psychiatric hospitalization, 15.9% had at least one same-day psychiatric hospitalization (information documented for 116patients), and 44.2% received at least one concomitant drug. Three cases of post-injection delirium/sedation syndrome were reported during the analysis period. Treatment emergent adverse events (incidence, 20.3%) were in line with the known profile of olanzapine. CONCLUSION: Patients were administered olanzapine pamoate and monitored in compliance with label recommendations. The safety profile assessment of olanzapine pamoate in actual conditions was consistent with that described in clinical studies.

Bk and Cf chromatographic separation and ²49Bk/²48Cm and ²49Cf/²48Cm elemental ratios determination by inductively coupled plasma quadrupole mass spectrometry.

The French Atomic Energy Commission has carried out several experiments for the study of minor-actinide transmutation processes in high intensity thermal neutron flux. In this context a Cm sample enriched in (248)Cm (∼97%) was irradiated in a thermal neutron flux at the High Flux Reactor (HFR) of the Laue-Langevin Institute (ILL). The precise and accurate determination of Cf isotope ratios and of (249)Bk/(248)Cm and (249)Cf/(248)Cm elemental ratios in the (248)Cm irradiated sample is crucial for the calculation of actinide neutron capture cross-sections. This work describes an analytical procedure for the separation and the isotope ratio measurement of Bk and Cf in the irradiated sample. The Bk and Cf separation is based on a lanthanides separation protocol previously developed by the laboratory. Well-defined retention times for Bk and Cf were obtained by coupling the Ionic Chromatography (IC) with an ICP-QMS. All conditions of element separation by IC and the different steps of the analytical protocol in order to obtain the isotopic and elemental ratios are presented. Relative uncertainties of Cf isotopic ratios range from 0.3% to 0.5% and the uncertainty of the (249)Bk/(248)Cm and (249)Cf/(248)Cm elemental ratios are respectively 6.1% and 3.2%. This level of uncertainty for both isotopic and elemental ratios is in perfect agreement with the requirement for transmutation studies.

Determination of (93)Zr decay scheme and half-life.

This study describes a new determination of the decay scheme and half-life of (93)Zr. A pure (93)Zr solution was obtained after chemical separation from the dissolution of an irradiated zircaloy sample. The concentration of (93)Zr in the solution was measured by mass spectrometry, with an isotopic dilution technique. The activity of the solution was measured by liquid scintillation counting, using an efficiency tracing method. The measurement of the activity concentration of (93)Nb(m) by X-ray spectrometry, allowed the determination of the (93)Zr decay scheme and the calculation of the (93)Zr detection efficiency. This leads to the calculation of the decay probability of (93)Zr toward (93)Nb(m) of (0.73+/-0.06) and to a half-life of (93)Zr of (1.64+/-0.06)x10(6) years. These values are discussed in comparison with the evaluated values available in the literature.

[Pattern and evolution of the prescription of olanzapine during one year: Results of the cohort study ECOL]. / Modalités et évolution de la prescription d'olanzapine : résultats de l'étude de cohorte ECOL.

INTRODUCTION: The necessary evidence of new therapies of clinical interest extends beyond clinical trials in a less controlled population and closer to clinical practice justified since several years the need of conducting observational, noninterventional studies. Observational studies must include epidemiological (quantitative observational) data to define prevalence and natural history of the target conditions. Moreover, pharmacological interventions in "naturalistic" patients populations, selected by clinicians as per clinical judgment within the scope of the target disease will allow to generate data to complement clinical trials. Clinical trials designed to show robust data on efficacy and tolerability particularly during registration trials must be complemented by robust observational research to confirm and better describe clinical effectiveness in the target population. A noninterventional, observational trial is a study where the medicinal product(s) is (are) prescribed in the usual manner in accordance with the terms of the marketing authorization. The assignment of the patient to a particular therapeutic strategy is not decided in advance by a trial protocol but falls within current practice and the prescription of the medicine is clearly separated from the decision to include the patient in the study. No additional diagnosis or monitoring procedures shall be applied to the patients and epidemiological methods shall be used for the analysis of collected data. Olanzapine is a new antipsychotic therapy registered in Europe for the treatment of schizophrenia since 1996. AIMS OF THE STUDY: The primary objective of this observational research was to study the evolution of the olanzapine dosage under naturalistic settings. Secondary objectives included patients characteristics, severity of disease, therapeutic evolution and coprescriptions, in a patient's cohort, suffering from schizophrenia, adult patients, diagnosis based on ICD-10; patients were followed during a total of 12 months. DESIGN OF THE STUDY: The cohort study was conducted in France. Between the period of June 2000 and February 2001, 407 psychiatrics randomized to participate in the study had consolidated the patient's cohort. RESULTS: A total of 1810 patients were included, 1093 (60, 4%) male, 717 (39, 6%) females. Age was recorded for a total of 1802 (99, 6%) patients, mean age was 37.8 years as per inclusion criteria and patients consent according to current regulations. Patients entered in the cohort as per clinicians decision underwent a treatment with olanzapine during an outpatient's consultation or at hospitalization. More than two thirds of the patients were followed up during 12 months after onset of this treatment. Clinical outcome was assessed at three, six, nine and 12 months following cohort inclusion using the following tools: CGI, PANSS, Calgary and GAF; as per CGI 78% of the patients cohort were severely ill, the mean PANSS score was 94.1. At second month of treatment clinicians were requested to very well document any changes in olanzapine dosage as well as reasons for the dosage modifications and potential coprescriptions. DISCUSSION: The daily mean dosage of olanzapine was 9.5mg at initiation of treatment, 10.5mg after one month and 11.2mg after 12 months of follow-up. The increase of the dosage after one month was associated with factors such as younger age, schizophrenia diagnosis and severity of the symptoms as measured by CGI and PANSS scores evolution, low initial dosage and hospitalization at treatment initiation. Within the 1810 participants included in the cohort, 1383 (76.5%) received a coprescrition of a psychotropic, for example, 811 (44.8%) a benzodiazepine, 506 (28.0%) an antidepressant. Among the patients cohort that were followed during 12 months, all the clinical and patient-functioning indicators progressed in the direction of a significant improvement.

[The European Schizophrenia Outpatient Health Outcomes Study: observational study over 36 months of the French cohort of schizophrenic outpatients treated with antipsychotics]. / Etude Schizophrenia Outpatient Health Outcomes (SOHO) France : étude observationnelle à 36 mois d'une cohorte de patients schizophrènes ambulatoires traités par antipsychotiques.

BACKGROUND: Studies describing long-term continuous care of outpatients with schizophrenia are relatively scarce. The prospective European Schizophrenia Outpatient Health Outcomes study (SOHO) provides data on a cohort of schizophrenic patients over a period of three years. METHODS: Prospective, long-term, observational study including outpatients who initiate therapy or change to a new antipsychotic. The study was designed to provide two patient groups of approximately equal size: treated either with olanzapine or a non-olanzapine antipsychotic. Sociodemographic, clinical and disease characteristics at baseline were described. Clinical severity of symptoms was assessed at each visit using the Clinical Global Impression scale (CGI). Treatment outcomes were analyzed as treatment discontinuation, remission and relapse rates. RESULTS: French results are presented in this report. Nine hundred and thirty-three patients (62% males) were recruited between March and December 2001. The mean age was 37.1+/-11.5 years. The mean time since first consultation for schizophrenia was 8.0+/-9.3 years. At study baseline, one quarter had paid employment, less than one third had a spouse or partner and more than half of them had an independent housing. Thirty percent of patients reported a previous suicide attempt. The mean CGI was 4.5+/-1.0 at admission. Overall, medication discontinuation for any cause occurred for 42% of patients. A remission (defined by a CGI

[Erysipelas, cellulitis and other severe Streptococcus pyogenes skin infections]. / Erysipèle, cellulites et autres infections cutanées sévères à Streptococcus pyogenes.

INCIDENCE AND GRAVITY: Invasive Streptococcus pyogenes infections are a common reason for hospitalization. Serious forms may occur in patients with no known risk factor, including young patients. Inversely, erysipela is observed more readily in the elderly population with a more vulnerable venous system. Disease gravity is related to the high risk of recurrence. For cellulitis, predominantly a disease of young subjects with no past history, severity is related to local extension and development of shock syndrome. Besides the immediate life-threatening situation, functional prognosis may be compromised, depending on the localization of the infection. PATHOGENESIS OF GROUP A STREPTOCOCCAL INFECTIONS: Adherence and invasion properties of group A streptococci, particularly the capsule and protein M, as well as streptococcal toxins cause severe septic and toxinic syndromes. Strains most frequently associated with invasive infections are: biotype 1, serotype M1 and biotype 3, serotype M3. TREATMENT: An antibiotic regimen by intravenous infusion of penicillin G is the gold standard treatment. Clindamycin should be added in case of septic shock. Extensive cellulitis or necrotizing fasciitis requires surgical debridement of the necrotic tissue and intensive care for the shock syndrome.

The DNA-binding protein II from Zymomonas mobilis. Complete amino acid sequence and interaction with DNA.

The primary structure of the DNA-binding protein II from Zymomonas mobilis has been determined from data provided by automated Edman degradation of the intact protein and of peptides derived from cleavage at aspartic acid and arginine residues. When compared with the homologous protein isolated from other bacteria, the DNA-binding protein II from Z mobilis shows many substitutions. Several non-conservative substitutions at positions usually highly conserved in this type of protein probably account for the weaker DNA-binding activity of this protein compared to that of the E coli protein.

Two regulatory elements of similar structure and placed in tandem account for the repressive activity of the first intron of the human apolipoprotein A-II gene.

Recent reports indicate that apolipoprotein (apo) A-II, the second most abundant protein of high-density lipoproteins, plays a crucial role in counteracting the beneficial effect of apo A-I against atherogenesis. Transcription of the human apo A-II gene is controlled by an enhancer comprising 14 regulatory elements located upstream of its promoter whereas the first intron of this gene behaves as a silencer. Here we show that two sequence elements account for the repressive activity of this intron and correspond to negative regulatory elements termed NRE I and NRE II. The activity of intron I and the nuclear proteins binding to NRE I and II are encountered in hepatic cells but not in non-hepatic cells studied here. Both NREs form nucleoprotein complexes of very similar physicochemical characteristics and bind the same or closely related proteins. Site-directed mutagenesis, transient transfection and gel-shift analysis experiments indicate that both NREs exhibit similar structures, being composed of two sites required for maximal activity and optimal binding of transcription factors. Therefore two negative regulatory elements of similar structure and function, placed in tandem, account for the repressive activity of the first intron of the human apo A-II gene. These NREs do not exhibit structural similarity with known NREs of other genes.

A novel homeodomain-encoding gene is associated with a large CpG island interrupted by the myotonic dystrophy unstable (CTG)n repeat.

Myotonic dystrophy (DM) is associated with a (CTG)n trinucleotide repeat expansion in the 3'-untranslated region of a protein kinase-encoding gene, DMPK, which maps to chromosome 19q13.3. Characterisation of the expression of this gene in patient tissues has thus far generated conflicting data on alterations in the steady state levels of DMPK mRNA, and on the final DMPK protein levels in the presence of the expansion. The DM region of chromosome 19 is gene rich, and it is possible that the repeat expansion may lead to dysfunction of a number of transcription units in the vicinity, perhaps as a consequence of chromatin disruption. We have searched for genes associated with a CpG island at the 3' end of DMPK. Sequencing of this region shows that the island extends over 3.5 kb and is interrupted by the (CTG)n repeat. Comparison of genomic sequences downstream (centromeric) of the repeat in human and mouse identified regions of significant homology. These correspond to exons of a gene predicted to encode a homeodomain protein. RT-PCR analysis shows that this gene, which we have called DM locus-associated homeodomain protein (DMAHP), is expressed in a number of human tissues, including skeletal muscle, heart and brain.

Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver.

Hepatocyte nuclear factor 4 (HNF-4) is a key transcription factor involved in the specific expression of many genes in liver and intestine. Sequences of cDNAs coding for HNF-4 have been established in rat and Drosophila melanogaster. Rat HNF-4 exhibits two isoforms which probably result from differential splicing. We have isolated HNF-4 cDNAs from an adult human cDNA library. Sequence analysis revealed that two HNF-4 isoforms are also present in human liver. The complete sequence of the longest human isoform has been established and compared to the rat HNF-4 amino-acid sequences.

Transcription of the human apolipoprotein A-II is down-regulated by the first intron of its gene.

Several reports indicate that apoA-II, the second most abundant HDL protein, plays a crucial role in modulating the anti-atherogenic behavior of HDL. Regulatory elements located 5' to the human apoA-II promoter have been previously described. In this paper we report that the first intron of the human apoA-II gene down-regulates its own promoter and the ubiquitous thymidine kinase promoter both in HepG2 and Caco-2 cells. The intron contains three sequences which bind nuclear proteins, thus demonstrating the presence of regulatory elements downstream of the transcription start site of the apoA-II gene.

YAC clone contigs surrounding the Zfx and Pola loci on the mouse X chromosome.

Pulsed-field mapping of a number of DNA markers in the Pola-Zfx region of the mouse X chromosome has established a genomic restriction map extending over 1.4 Mb. A number of YAC clones from the Pola-Zfx region have been isolated from three mouse YAC libraries--first, a mouse C57BL/10 partial R1 YAC library constructed in a yeast strain carrying a rad52 mutation (Chartier et al. (1992) Nature Genetics 1: 132-136); second, a mouse C3H partial R1 library (Larin et al. (1991) Proc. Natl. Acad. Sci. USA 88: 4123-4127); and third, a mouse C57BL/6 partial R1 library (Burke et al. (1991) Mamm. Genome 1:65). Six YAC clones encompass the Zfx-Pola region, confirming the linkage of the Pola and Zfx loci and establishing a physical map order in this region of cen-Pola-DXCrc140-DXCrc57-Zfx-tel. The close linkage of Pola and Zfx in the mouse genome suggests that the POLA and ZFX loci must also be closely linked on the human X chromosome.

Construction of a mouse yeast artificial chromosome library in a recombination-deficient strain of yeast.

We have constructed a new generation yeast artificial chromosome (YAC) library from female C57BL/10 mice in a recombination-deficient strain of Saccharomyces cerevisiae carrying a mutation in the RAD52 gene. The YAC library contains 41,568 clones with an average insert size of 240 kilobases, representing a greater than threefold coverage of the mouse genome. Currently, the library can be screened by polymerase chain reaction and we have isolated positive clones at a number of loci in the mouse genome. This rad52 library should enable a long-term assessment of the effect of one of the yeast recombination pathway genes on both, genome-wide YAC clone stability and the frequency of chimaeric clones.

Determination of the DNA-interacting region of the archaebacterial chromosomal protein MC1. Photocrosslinks with 5-bromouracil-substituted DNA.

Protein MC1 is the major chromosomal protein in methanosarcinaceae. Using photochemical crosslinking on 5-bromouracil-substituted DNA, we identified the region of the protein that interacts with it. This region is located in the C-terminal part of the polypeptide chain, and the crosslinked amino-acids are in the region 74-86. Tryptophan 74 is one of the amino-acids crosslinked to DNA.

[A new case of Mycobacterium bovis pulmonary tuberculosis in the dromedary (Camelus dromedarius) in Mauritania]. / Un nouveau cas de tuberculose pulmonaire à Mycobacterium bovis chez le dromadaire (Camelus dromedarius) en Mauritanie.

A case of pulmonary tuberculosis is described in a dromedary from Nouakchott (Mauritania). Gross lesions affected pulmonary parenchyma, diaphragmatic pleura, pericardium and regional lymph nodes: caseo-calcified nodules, miliary tubercles and haemorrhagic "pendeloques". Microscopically lesions were characterised by granulomatous tissue, epithelioid cells, necrotic material in the centre. No Langhans giant cells were seen. Mycobacterium bovis was isolated from these samples.