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Joël Constans,Christine Germain,Philippe Gosse,Jacques Taillard,Kiet Tiev,Isabelle Delevaux,Luc Mouthon,Claude Schmidt,Florence Granel,Pascale Soria,François Lifermann,Gabriel Etienne,Fabrice Bonnet,Karim Zoulim,Dominique Farge-Bancel,Isabelle Marie,Yannick Allanore,Jean Cabane,Alain Amonchot,Isabelle Macquin-Mavier,Marianne Saves,Faiez Zannad,Claude Conri,ERAMS investigators  OBJECTIVE: The ERAMS study addressed the value of arterial stiffness in predicting the severity of systemic sclerosis. METHODS: ERAMS was a prospective multicentre cohort study including patients with definite systemic sclerosis. Arterial stiffness was measured by the standardized non-invasive QKd ... ( view more )100-60 method. Clinical evaluation, biological measurements, functional respiratory tests and cardiac Doppler echography were performed at inclusion then each year until 3 years' follow-up was completed. Progression was defined as mild (articulations, muscle, oesophagus or skin involvement) or severe (lung, heart or kidney involvement) by a critical event committee. The prediction of severe progression was studied for QKd 100-60 as well as clinical and biological data at baseline by univariate and multivariate analysis. RESULTS: Ninety-nine patients were included (81 women, 18 men, mean age 57 years, standard deviation 12.5). Although their blood pressure profile was normal, half the patients had increased arterial stiffness (QKd 100-60<200 ms). There was a significant relationship between age-adjusted arterial stiffness and decrease in carbon dioxide diffusion (P<0.03) or haemoglobin rate (P<0.01). By univariate analysis, severe progression after 3 years was predicted by age (P=0.04), lung involvement (P=0.04), diffusion of lung carbon oxide (DLCO) (P<0.01), skin score (P=0.02), haemoglobin (P<0.01) and baseline Qkd 100-60 divided into two classes according to the median (P<0.01). By multivariate analysis, only haemoglobin rate [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.2-0.9] and QKd 100-60 (OR 19.6, 95% CI 1.2-308.2) predicted severe progression of systemic sclerosis. CONCLUSION: The measurement of arterial stiffness by the QKd method is a useful objective method for assessing the prognosis of systemic sclerosis independently from other data. ( view less ) Luis Fraile Calle,María José Bueno Núñez,María Josefa Flores Sánchez,María Isabel Mateos Hernández,María Yolanda García Morán,Pilar Iñigo Garzón,Natividad Gómez Bautista,María Teresa Hernández Manzano,Ana Isabel Martín Alonso,María Celeste Martín Alonso,Inés María Nieto Benito,Florinda Pérez Ciudad,Ruth Prieto Román,Carmen Sánchez Blázquez,Isabel Ramos Sevillano,María Cruz Vicente Elvira The use of the scientific method in research and investigation in nursing requires avoiding subjectivity at all times. Professionals obtain data by means of instruments which must be operative, valid and reliable. The authors develop and verify two instruments: a nine question opinion poll which us... ( view more )es tests and retests, having a 93-40% concordance proportion. A Likert type attitude scale, applying the "t" in Student to 59 initial propositions, obtaining a definitive scale having 7 positive items and 7 negative ones which gave a 95% confidence level of statistical meaning for a bilateral test and which had 22 degrees of liberty. This study took place using a pilot group of 43 nurses, it was a practical shop exercise on research in nursing occurred in the Hospital, organized by the Nursing Administration and taught by the group coordinator. ( view less ) Antonio Gutiérrez,Isabel Muñoz,Carlos Solano,Isabel Benet,Concepción Gimeno,Isabel Marugán,María Dolores Gea,Javier García-Conde,David Navarro Early reconstitution of lymphoid populations was monitored by immunophenotyping in 57 allogeneic peripheral blood stem cell (allo-PBSC) transplant patients either with or without cytomegalovirus (CMV) viremia or disease. Cell counts for total lymphocytes and CD4(+) T cells above the percentile 60th... ( view more ) at day 14 postransplant were associated significantly with CMV viremia-free survival within 120 days after transplant. Recovery of total lymphocyte, CD3(+), and CD8(+) T-cell counts proceeded at a more rapid rate in CMV viremic patients than in nonviremic patients, irrespective of whether preemptive treatment with ganciclovir had been prescribed. Significant expansion of CD8(+) and CD8(+) CD57(+) T-cell subsets was associated with recovery from viremia and no progression to CMV disease. Immunophenotyping may provide useful information for the clinical management of CMV infection in allo-PBSC transplant recipients. ( view less ) Aurora Fontan,Ana Rojo,Rosario Sanchez Pernaute,Isabel Hernández,Isabel López,Carlos Castilla,Julio Sanchez Albisua,Antonio Perez Higueras,Imad Al-Rashid,Alberto Rabano,Isabel Gonzalo,Maria Angeles Mena,Alex Cools,Silvia Eshuis,Paul Maguire,Jan Pruim,Klaus Leenders,Justo Garcia de Yebenes Parkinson's disease (PD) is a common neurodegenerative disorder that produces progressive disability despite symptomatic treatment. Several strategies, including stereotaxic brain lesions, deep brain stimulation, transplants of dopamine cells and administration of neurotrophic factors, have been pr... ( view more )oposed to improve efficacy and to counteract the progression of the disease. We here report the effects of repetitive intracerebral infusion of basic fibroblast growth factor (bFGF) and glial-derived neurotrophic factor, up to 1 year, in Cynomolgus monkeys with long standing asymmetric parkinsonism produced by unilateral intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The treatment with neurotrophic factors was initiated when the parkinsonian deficits were stable, 6 months after the administration of MPTP. The evaluation of the response to the neurotrophic factors was performed by blind observers using: clinical scales that measured global motor deficit, motor ability in both hands, apomorphine-induced rotation, determination of the levels of monoamine metabolites in cerebrospinal fluid, and 6-F18-fluoro-l-DOPA (F-DOPA) uptake in the striatum and histology. Both factors, but bFGF more so, improve motor behavior, dopamine metabolism, striatal F-DOPA uptake, and the number of dopamine neurons. The procedure is well tolerated and provides a strong background for efficacy and safety of this treatment in patients with PD. ( view less ) Sonia Morante-Zarcero,Isabel Del Hierro,Mariano Fajardo,Isabel Sierra A simple and rapid HPLC method has been developed using a polysaccharide chiral stationary phase (Chiralpak AD-H) for the resolution of glycidyl tosylate enantiomers. These compounds were obtained by asymmetric epoxidation of allyl alcohol with chiral titanium-tartrate complexes as catalyst after i... ( view more )n situ derivatization of the intermediate glycidols. Separations were achieved using two types of mobile phase: a normal-phase (n-hexane), and a polar-phase (methanol or acetonitrile). The influence of the type and concentration of organic modifier in the mobile phase (ethanol or 2-propanol), the flow rate and the column temperature was investigated. In normal-phase mode, the optimized conditions were: n-hexane/ethanol 70/30 (v/v) at a flow rate of 1.2mLmin(-1) and 40 degrees C. In polar-phase mode, the optimized conditions were: methanol at a flow rate of 0.8mLmin(-1) and 20 degrees C. In both cases, analysis time was =11min and the chiral resolution was >/=2. Nevertheless, due to the better Rs obtained in normal-phase mode, only this method was validated to avoid peaks overlapping in real samples. This method was found to be linear in the 5-300mugmL(-1) range (R(2)>0.999) with an LOD of 1.5mugmL(-1) for both glycidyl tosylate enantiomers. Repeatability and intermediate precision at three different concentrations levels were below 0.5 and 7.2% R.S.D. for retention time and area, respectively. This method was applied successfully for the determination of glycidyl tosylate enantiomers after in situ derivatization of glycidols obtained in allylic alcohol asymmetric epoxidation processes with chiral titanium-tartrate complexes as catalysts. ( view less ) Cédric Laguri,Isabelle Duband-Goulet,Nikolas Friedrich,Marianne Axt,Pascal Belin,Isabelle Callebaut,Bernard Gilquin,Sophie Zinn-Justin,Joël Couprie The eukaryotic mismatch repair (MMR) protein MSH6 exhibits a core region structurally and functionally similar to bacterial MutS. However, it possesses an additional N-terminal region (NTR), comprising a PCNA binding motif, a large region of unknown function and a nonspecific DNA binding fragment. ... ( view more )Yeast NTR was recently described as an extended tether between PCNA and the core of MSH6 . In contrast, we show that human NTR presents a globular PWWP domain in the region of unknown function. We demonstrate that this PWWP domain binds double-stranded DNA, without any preference for mismatches or nicks, whereas its apparent affinity for single-stranded DNA is about 20 times lower. The S144I mutation, which in human MSH6 causes inherited somatic defects in MMR resulting in increased development of hereditary non polyposis colorectal cancer , is located in the DNA binding surface of the PWWP domain. However, it only moderately affects domain stability, and it does not perturb DNA binding in vitro. ( view less ) Antonio Otero,Juan Fernández-Baeza,Agustín Lara-Sánchez,Antonio Antiñolo,Juan Tejeda,Emilia Martínez-Caballero,Isabel Márquez-Segovia,Isabel López-Solera,Luis F Sánchez-Barba,Carlos Alonso-Moreno Reaction of hybrid scorpionate/cyclopentadienyl ligands in the form of the lithium derivatives [Li(bpzcp)(THF)] [bpzcp=2,2-bis(3,5-dimethylpyrazol-1-yl)-1,1-diphenylethylcyclopentadienyl], [Li(bpztcp)(THF)] [bpztcp=2,2-bis(3,5-dimethylpyrazol-1-yl)-1-tert-butylethylcyclopentadienyl], and the in sit... ( view more )u-generated "Li(bpzpcp)" [bpzpcp=2,2-bis(3,5-dimethylpyrazol-1-yl)-1-phenylethylcyclopentadienyl] with MCl3(THF)3 afforded the group 3 halide compounds [MCl2(bpzcp)(THF)] (M=Sc, 1; Y, 2), [MCl2(bpztcp)(THF)] (M=Sc, 3; Y, 4), and [MCl2(bpzpcp)(THF)] (M=Sc, 5; Y, 6). The H2O adduct of 4, [YCl2(bpztcp)(H2O)] (7), was formed when a solution of 4 was allowed to stand at room temperature in the presence of moisture. Complexes 1-7 adopt a pseudo-octahedral structure with heteroscorpionate ligands kappa2-NNeta5-Cp coordinated to the metal through the cyclopentadienyl group and two imino nitrogens of pyrazole rings. The alkyl heteroscorpionate scandium and yttrium complexes recently reported by our group, [M(CH2SiMe3)2(bpzcp)], react with 2,6-dimethylphenol and 3,5-dimethylphenol to give the bis(aryloxide) derivatives [M(OAr)2(bpzcp)] (M=Sc, OAr=2,6-dimethylphenoxide, 8; M=Y, OAr=2,6-dimethylphenoxide, 9; M=Y, OAr=3,5-dimethylphenoxide, 10). Complex 9 underwent an interesting hydrolysis process to give the tetranuclear complex [{Y(bpzcp)}(micro-OH)2(micro3-OH){Y(OAr)2}]2 (11). Variable-temperature 1H NMR experiments on 9 and 10 revealed a rapid fluxional exchange between coordinated and noncoordinated pyrazolyl rings, producing interconversion between the two enantiomers in which the scorpionate ligand can be coordinated in a kappa1-Neta5-Cp form. The structures of the complexes were determined by spectroscopic methods and the X-ray crystal structures of 2, 7, and 11 were also established. Complexes 1 and 2 are active olefin polymerization catalysts after activation with methylaluminoxane. These compounds gave atactic polystyrenes with narrow molecular weight distribution (Mn/Mw 1.26-1.91) and with low molecular weights. ( view less ) Julie Duval,Claude M J Braun,Isabelle Montour-Proulx,Sylvie Daigneault,Isabelle Rouleau,Jean Bégin A growing literature suggests that early lesions are associated with poorer IQ outcome. Those studies covered a restricted age range in pediatric populations only and did not control for important moderator variables. The present investigation studied IQ change in brain-lesioned children and adults... ( view more ) (age 0 to 84 years). Altogether, 725 cases with a documented unilateral focal lesion were gathered from hospital charts and from published cases in the literature, including 240 with repeated IQ testing. Multiple regression analyses isolated the contribution of age at lesion onset to IQ change. Important mediator variables included were lesion side, site, volume, etiology, and so on. An early lesion was significantly associated with poorer postlesion IQ in time and with decline of IQ in time. Later onset lesions were associated with better postlesion IQ and recovery in time. The so-called Kennard principle is refuted, with regard to IQ. ( view less ) Halisson Bastos,Paula Fabiana Sobral da Silva,Marco Antônio Veloso de Albuquerque,Adriana Mattos,Rudimar Santos Riesgo,Lygia Ohlweiler,Maria Isabel Bragatti Winckler,José Augusto Bragatti,Rodrigo Dias Duarte,Denise Isabel ZandonáThe authors report two cases of Brazilian children with most of the common syndromic features of Proteus syndrome, such as asymmetric overgrowth of tissues, skin abnormalities, hypotonia and mental retardation. In both patients, a refractory epilepsy, compatible with Ohtahara syndrome, as well as h... ( view more )emimegalencephaly, with asymmetric distribution of facial fat, were also diagnosed. ( view less ) Manuel Pazos,Ana Alonso,Isabel Sánchez,Isabel Medina Hydroxytyrosol, a natural phenolic compound obtained from olive oil byproduct, was characterized as an antioxidant in three different foodstuffs rich in fish lipids: (a) bulk cod liver oil (40% of omega-3 PUFAs), (b) cod liver oil-in-water emulsions (4% of omega-3 PUFAs), and (c) frozen minced hors... ( view more )e mackerel ( Trachurus trachurus) muscle. Hydroxytyrosol was evaluated at different concentration levels (10, 50, and 100 ppm), and its antioxidant capacity was compared against that of a synthetic phenolic, propyl gallate. Results proved the efficiency of hydroxytyrosol to inhibit the formation of lipid oxidation products in all tested food systems, although two different optimal antioxidant concentrations were observed. In bulk oil and oil-in-water emulsions, a higher oxidative stability was achieved by increasing the concentration of hydroxytyrosol, whereas an intermediate concentration (50 ppm) showed more efficiency, delaying lipid oxidation in frozen minced fish muscle. The endogenous depletion of alpha-tocopherol and omega-3 polyunsaturated fatty acids (omega-3 PUFAs) was also inhibited by supplementing hydroxytyrosol in minced muscle; however, the consumption of the endogenous total glutathione was not efficiently reduced by either hydroxytyrosol or propyl gallate. A concentration of 50 ppm of hydroxytyrosol was best to maintain a longer initial level of alpha-tocopherol (approximately 300 microg/g of fat), whereas both 50 and 100 ppm of hydroxytyrosol were able to preserve completely omega-3 PUFAs. Hydroxytyrosol and propyl gallate showed comparable antioxidant activities in emulsions and frozen fish muscle, and propyl gallate exhibited better antioxidant efficiency in bulk fish oil. ( view less ) Agnes Rigouzzo,Laure Girault,Nicolas Louvet,Frederique Servin,Tom De-Smet,Veronique Piat,Robert Seeman,Isabelle Murat,Isabelle Constant BACKGROUND: In this prospective study, we compared the relationship between propofol concentrations and bispectral index (BIS) in children versus young adults anesthetized with target-controlled infusion (TCI) of propofol. METHODS: Forty-five prepubertal subjects (children) and 45 postpubertal subj... ( view more )ects (adults) were studied. All patients were anesthetized with TCI of propofol, based on the Kataria et al.'s model for children and on the Schnider et al.'s model for adults. All data from the BIS and the TCI system were continuously recorded using Rugloop software. Remifentanil was continuously administered throughout the study (0.25 microg x kg(-1) x min(-1)). In all patients, after the end of surgery, a 12-min period with a stable target plasma concentration (Ct) of propofol, randomly assigned at 2, 3, 4, 5, and 6 microg/mL, was performed. In addition, in most of the patients, another 12-min period was performed during which the BIS was targeted at 50 +/- 5. After each 12-min steady-state period, the Ct and BIS were noted and the plasma concentration of propofol was measured (Cm). The Ct and Cm corresponding to half maximal effect (BIS(50)) was determined by the Hill equation, and by targeting BIS at 50. RESULTS: In children, as in adults, BIS values were highly correlated with the corresponding Ct or Cm of propofol following classical E(max) dose-response curves. The ECt(50) and the ECm(50), derived from the dose-response curves, were higher in children than in adults: ECm(50): 4.0 (3.6-4.5) microg/mL vs 3.3 (3.0-3.7) microg/mL [mean (95% CI)], P < 0.001; as well were the Ct and Cm clinically obtained when BIS was targeted at 50 (Cm(50): 4.3 +/- 1.1 microg/mL vs 3.4 +/- 1.2 microg/mL, (mean +/- SD) P < 0.05, children versus adults). Cm was generally under-estimated by the Ct, and the bias was higher in children than in adults: 2.6 +/- 2.6 microg/mL vs 1.7 +/- 1.6 microg/mL (P = 0.05). CONCLUSIONS: The good relationship between propofol and BIS demonstrated in children as in adults suggested a slightly lower sensitivity to propofol in children. As the predictability of plasma propofol concentrations with the classical pharmacokinetic/pharmacodynamic models is limited in children, a cerebral pharmacodynamic feedback, such as BIS, may be useful in this population. ( view less ) Ma de la Encina Arias,Isabel Cantarino,Paloma de la Quintana,Ma Antonia Estrada,Fernández Adelina,F J Martínez,Ma Carmen Martínez,Dolores Martínez,Lourdes Mateos,Teresa Poca,Dolores Ruiz,Fuensanta Salvador,Ma Isabel Sánchez,Esperanza VillalbaThe authors publish the first precise, specific, valid questionnaire in Spanish which measures the quality of life related to health for patients who have undergone an intestinal or urological ostomy; furthermore, this questionnaire has been validated in a sample of Spanish population. The OPM Divi... ( view more )sion of B. Braun Medical was the sponsor of the study which led to the creation of this QUALYPOLL questionnaire. Statistical validation of the data complied was performed by Health Outcomes Research Europe which carried out a multi-centric national study to evaluate the measuring properties of the aforementioned QUALYPOLL questionnaire on patients who have undergone an intestinal or urological ostomy. ( view less ) Isabel C Garcés-Palacio,Maja Altarac,Isabel C Scarinci BACKGROUND: With the rising influx of Hispanics to the United States, there is an ongoing need to promote health and wellness care to this non-English-speaking, minority population group. Programs, specifically developed to address the unique cultural mores of Hispanics, need to focus on increasing... ( view more ) knowledge about health issues, particularly in the area of reproductive health. A study was conducted in Memphis, TN, to examine the differences between low-income Hispanic immigrants' and low-income non-Hispanics' (1) contraceptive use; (2) reproduction and contraception knowledge; as well as (3) the demographic and knowledge factors associated with their choice of contraceptive, in order to better formulate successful educational programs for area Hispanics. STUDY DESIGN: A cross-sectional survey of 226 women, recruited through a federal assistance program in Tennessee, was performed over a 5-month period in 2000 to 2001. Women, between the ages of 18 and 42, were individually interviewed to learn more about their reproduction knowledge and method of contraception. RESULTS: This study found that knowledge about reproduction and contraceptive use was significantly lower among Hispanics than non-Hispanics. Furthermore, contraceptive use was significantly lower among Hispanics than among non-Hispanics. Hispanics were less likely to use the oral contraceptive or have a tubal ligation, preferring injectable contraceptive. Non-Hispanics, who were more likely to use contraceptive methods, were less likely to use injectables, preferring the oral contraceptive. Among Hispanics, knowledge about contraceptives, number of children and marital status were associated with contraceptive use. Among non-Hispanics, only education was associated with contraceptive use. CONCLUSION: Interventions targeting Hispanic immigrants should be developed to increase their knowledge about contraceptive methods. ( view less ) Frédérique Maurice,Isabelle Broutin,Isabelle Podglajen,Philippe Benas,Ekkehard Collatz,Frédéric Dardel The emergence of multi-resistant pathogenic bacteria is a worldwide health issue. Recently, clinical variants of a single antibiotic-modifying acetyltransferase, AAC(6')-Ib-a variant of aminoglycoside 6'-N-acetyltransferase-have been identified that confer extended resistance to most aminoglycoside... ( view more )s and, more surprisingly, to structurally unrelated fluoroquinolones. The corresponding gene is carried by mobile genetic elements and is present in most multi-resistant pathogenic strains, hence making it a serious threat to current therapies. Here, we report the crystal structures of both narrow- and broad-spectrum resistance variants of this enzyme, which reveal the structural basis for the emergence of extended resistance. The active site shows an important plasticity and has adapted to new substrates by a large-scale gaping process. We have also obtained co-crystals with both substrates, and with a simple transition state analogue, which provides new clues for the design of inhibitors of this resistance mechanism. ( view less ) Nina Papazova,Rim Ghedira,Sabine Van Glabeke,Aghleb Bartegi,Pieter Windels,Isabel Taverniers,Isabel Roldan-Ruiz,Erik Van Bockstaele,Anne Milcamps,Guy Van Den Eede,Ann Depicker,Marc De Loose Genetic transformation is often associated with different rearrangements of the plant genome at the site of insertion. Therefore the question remains weather these T-DNA insertion sites are more prone to genotoxic stresses. Here, we studied the impact of propagation through generations, the influen... ( view more )ce of gene stacking and of photo oxidative stress caused by high light intensity on the stability of the transgene flanking regions in the model plant Arabidopsis thaliana. Conformational Sensitive Capillary Electrophoresis (CSCE), RFLP and sequencing were deployed in this analysis in order to study the proximal 100 bp and the long-range T-DNA flanking sequences. By screening seven transgenic lines no evidence for occurrence of mutation events were found, implying that the nucleotide sequence of the T-DNA flanking regions of the studied events is unlikely to be unstable. ( view less ) Angela Stefanachi,Jose Manuel Brea,Maria Isabel Cadavid,Nuria B Centeno,Cristina Esteve,Maria Isabel Loza,Ana Martinez,Rosa Nieto,Enrique Raviña,Ferran Sanz,Victor Segarra,Eddy Sotelo,Bernat Vidal,Angelo Carotti A large series of piperazin-, piperidin- and tetrahydroisoquinolinamides of 4-(1,3-dialkyl-9-deazaxanthin-8-yl)phenoxyacetic acid were prepared through conventional or multiple parallel syntheses and evaluated for their binding affinity at the recombinant human adenosine receptors, chiefly at the h... ( view more )A(2B) and hA(2A) receptor subtypes. Several ligands endowed with high binding affinity at hA(2B) receptors, excellent selectivity over hA(2A) and hA(3) and a significant, but lower, selectivity over hA(1) were identified. Among them, piperazinamide derivatives 23 and 52, and piperidinamide derivative 69 proved highly potent at hA(2B) (K(i)=11, 2 and 5.5 nM, respectively) and selective towards hA(2A) (hA(2A)/hA(2B) SI=912, 159 and 630, respectively), hA(3) (hA(3)/hA(2B) SI=>100, 3090 and >180, respectively) and hA(1) (hA(1)/hA(2B) SI=>100, 44 and 120, respectively), SI being the selectivity index. A number of selected ligands tested in functional assays in vitro showed very interesting antagonist activities and efficacies at both A(2A) and A(2B) receptor subtypes, with pA(2) values close to the corresponding pK(i)s. Structure-affinity and structure-selectivity relationships suggested that the binding potency at the hA(2B) receptor may be increased by lipophilic substituents at the N4-position of piperazinamides and that an ortho-methoxy substituent at the 8-phenyl ring and alkyl groups at N1 larger than the ones at N3, in the 9-deazaxanthine ring, may strongly enhance the hA(2A)/hA(2B) SI. ( view less ) Anne Laprie,Isabelle Catalaa,Emmanuelle Cassol,Tracy R McKnight,Delphine Berchery,Delphine Marre,Jean-Marc Bachaud,Isabelle Berry,Elizabeth Cohen-Jonathan Moyal PURPOSE: To investigate the association between magnetic resonance spectroscopic imaging (MRSI)-defined, metabolically abnormal tumor regions and subsequent sites of relapse in data from patients treated with radiotherapy (RT) in a prospective clinical trial. METHODS AND MATERIALS: Twenty-three exa... ( view more )minations were performed prospectively for 9 patients with newly diagnosed glioblastoma multiforme studied in a Phase I trial combining Tipifarnib and RT. The patients underwent magnetic resonance imaging (MRI) and MRSI before treatment and every 2 months until relapse. The MRSI data were categorized by the choline (Cho)/N-acetyl-aspartate (NAA) ratio (CNR) as a measure of spectroscopic abnormality. CNRs corresponding to T1 and T2 MRI for 1,207 voxels were evaluated before RT and at recurrence. RESULTS: Before treatment, areas of CNR2 (CNR > or =2) represented 25% of the contrast-enhancing (T1CE) regions and 10% of abnormal T2 regions outside T1CE (HyperT2). The presence of CNR2 was often an early indicator of the site of relapse after therapy. In fact, 75% of the voxels within the T1CE+CNR2 before therapy continued to exhibit CNR2 at relapse, compared with 22% of the voxels within the T1CE with normal CNR (p < 0.05). The location of new contrast enhancement with CNR2 corresponded in 80% of the initial HyperT2+CNR2 vs. 20.7% of the HyperT2 voxels with normal CNR (p < 0.05). CONCLUSION: Metabolically active regions represented a small percentage of pretreatment MRI abnormalities and were predictive for the site of post-RT relapse. The incorporation of MRSI data in the definition of RT target volumes for selective boosting may be a promising avenue leading to increased local control of glioblastomas. ( view less ) César Valenzuela-Encinas,Isabel Neria-González,Rocio J Alcántara-Hernández,J Arturo Enríquez-Aragón,Isabel Estrada-Alvarado,César Hernández-Rodríguez,Luc Dendooven,Rodolfo Marsch The soil of the former lake Texcoco is an extreme environment localized in the valley of Mexico City, Mexico. It is highly saline and alkaline, where Na(+), Cl(-), HCO (3) (-) and CO (3) (2-) are the predominant ions, with a pH ranging from 9.8 to 11.7 and electrolytic conductivities in saturation ... ( view more )extracts from 22 to 150 dS m(-1). Metagenomic DNA from the archaeal community was extracted directly from soil and used as template to amplify 16S ribosomal gene by PCR. PCR products were used to construct gene libraries. The ribosomal library showed that the archaeal diversity included Natronococcus sp., Natronolimnobius sp., Natronobacterium sp., Natrinema sp., Natronomonas sp., Halovivax sp., "Halalkalicoccus jeotgali" and novel clades within the family of Halobacteriaceae. Four clones could not be classified. It was found that the archaeal diversity in an alkaline-saline soil of the former lake Texcoco, Mexico, was low, but showed yet uncharacterized and unclassified species. ( view less ) Isabelle Di Centa,Marc Coggia,Pierre Cerceau,Isabelle Javerliat,Pascal Alfonsi,Alain Beauchet,Olivier Goëau-Brissonnière We describe early and mid-term results of total laparoscopic aortofemoral bypass (TLAFB). TLAFB was performed in 150 cases of severe aortoiliac occlusive disease. Aortic approaches included transperitoneal left retrocolic (n = 86), left retrorenal (n = 51), and direct (n = 4); the retroperitoneosco... ( view more )pic approach was used in nine cases. The procedure was totally laparoscopic in 145 patients (96.6%). Median operative and clamping times were 260 (120-450) and 81 (36-190) min, respectively. Thirty-day mortality was 2.7%. Nonlethal systemic, local vascular, and local nonvascular complications occurred in 21 (14.3%), seven (4.8%), and two (1.3%) patients, respectively. Median return to general diet and ambulation were, respectively, days 2 and 3. Median hospital stay was 7 days. Follow-up was 25.2 +/- 17.6 months (range 1-60) with 3-year primary and secondary actuarial patency rates of 93% and 95.6%, respectively. TLAFB gives early and mid-term patency rates comparable to open direct repair. Laparoscopy allows faster recovery and reduces operative trauma. ( view less ) Isabelle Chaudieu,Isabelle Beluche,Joanna Norton,Jean-Philippe Boulenger,Karen Ritchie,Marie Laure Ancelin BACKGROUND: Cortisol secretion in elderly persons with anxiety disorders exposed to common stressful situations has not been evaluated. METHODS: Salivary-free cortisol levels were evaluated at 8, 15, and 22 h, in 201 elderly subjects during stressful and non-stressful days. Psychiatric symptomatolo... ( view more )gy was assessed by a standardized psychiatric examination (MINI). RESULTS: Elderly subjects without psychiatric disorder showed a sustained increase in cortisol secretion several hours after the exposure to a stressful situation. In comparison, subjects with anxiety disorders showed a greater increase in cortisol secretion in the stressful situation, with lowered recuperation capacity. This effect was dose-dependent as a function of anxiety co-morbidity. Persons reporting lifetime major trauma with intrusions exhibited lowered continuous basal cortisol associated with efficient recuperation capacity. Independently of psychopathology, women appeared more reactive to stressful environmental conditions. LIMITATIONS: Exclusion of institutionalized persons and benzodiazepine users may have led to sampling of less severe anxiety symptoms. CONCLUSIONS: Dysregulation of the hypothalamic-pituitary-adrenal axis was observed in elderly persons with anxiety disorders experiencing environmental stress. A common pattern of up-regulated diurnal cortisol secretion was observed in anxious subjects with lifetime and current anxiety disorder irrespective of sub-type (generalized anxiety, phobias) suggesting a stable trait and a common "core" across disorders. Elderly persons who had experienced trauma with subsequent intrusions showed a distinct pattern with down-regulated activity. ( view less ) Bénédicte Rennesson-Rey,Anne-Christine Rat,Isabelle Chary-Valckenaere,Isabelle Bettembourg-Brault,Nadine Juge,Hervé Dintinger,Jacques Pourel,Damien Loeuille OBJECTIVE: To evaluate the influence of a joint effusion on the clinical response to a single injection of Hylan GF-20 for hip osteoarthritis. METHOD: We prospectively included patients scheduled for intraarticular Hylan GF-20 injection to treat hip osteoarthritis. Disease severity was assessed bas... ( view more )ed on the Kellgren-Lawrence radiological grade. Ultrasonography was performed to look for a joint effusion. The pain score on a visual analog scale, Lequesne algofunctional index, and WOMAC scores were recorded at baseline and 1, 3, and 6 months postinjection. The proportions of patients who met OARSI response criteria and who achieved Patient Acceptable Symptom State (PASS) thresholds were determined in the overall population and in the groups with and without a joint effusion at baseline. RESULTS: Of 55 included patients, 24 (44%) had an effusion at baseline. The baseline Lequesne index was significantly higher in the group with an effusion (11.9+/-3.6 versus 8.4+/-4.5) (p=0.003). The proportions of OARSI responders in the overall population were 31.8%, 39.4%, and 14.8% after 1, 3, and 6 months, respectively. The proportions of patients who achieved the PASS for pain and function were 52.4% and 50.0% after 1 month, 67.7% and 54.5% after 3 months, and 60.0% and 50.0% after 6 months, respectively. Presence of an effusion at baseline had no effect on any of the clinical response parameters. CONCLUSION: Presence of a joint effusion is associated with worse pain and functional impairment at baseline but has no influence on the clinical response to Hylan GF-20 in patients with hip osteoarthritis. ( view less ) Ana Martínez,Hugo Gutiérrez-de-Terán,José Brea,Enrique Raviña,Maria Isabel Loza,Maria Isabel Cadavid,Ferran Sanz,Bernat Vidal,Victor Segarra,Eddy Sotelo A collection of 25 2-(2'-furyl)-1,2,4-triazolo[1,5-a]quinoxalines incorporating different substitution patterns at position 4 have been synthesized and their binding affinity towards human adenosine receptors (hA(1), hA(2A), hA(2B) and hA(3)) was determined. The biological data show that several po... ( view more )tent at hA(1), but lightly selective, adenosine ligands were identified. Moreover, these results confirmed the hypothesis that the structural modifications carried out on the 4-position of the tricyclic system produces a remarkable modification of the adenosine receptorial profile. A 3D-QSAR modelling study (GRIND/ALMOND methodology) performed on the hA(1) data gave further support to the pharmacological results, and it is presented as a useful tool for the future design of ligands with better pharmacological profiles. ( view less ) Bénédicte Rhoné,Carine Remoué,Nathalie Galic,Isabelle Goldringer,Isabelle Bonnin Experimental populations evolving under natural selection represent an interesting tool to study genetic bases of adaptation. Evolution of genes possibly involved in adaptive response can be followed together with the corresponding phenotypic traits. Using experimental populations of hexaploid whea... ( view more )t, we studied the evolution of flowering time, a major adaptive trait that synchronizes the initiation of reproduction and the occurrence of favourable environmental conditions. During 12 generations, three populations were grown in contrasted environments (Vervins North France, Le Moulon near Paris, Toulouse South France) under the influence of natural selection, drift, mutation and recombination. Evolution of diversity at the major gene VRN-1 involved in wheat vernalization response has been analysed jointly with earliness estimated in controlled conditions. Whatever the population, rapid phenotypic changes as well as parallel genotypic variations were observed in the first seven generations, probably as the result of selection acting on this major gene which explains 80% of the trait variation overall. Different allelic combinations at physically unlinked copies of VRN-1 located on distinct genomes (A, B and D) were selected between populations. As theoretically expected, due to population differentiation, a high level of genetic diversity was maintained overall in generation 12. Surprisingly, in two populations out of three, the emergence of new alleles by mutation or migration, coupled with temporal variable selection or frequency-dependent selection, allowed to maintain within-population diversity despite local genetic drift and natural selection. This result may plead for an evolutionary approach of wheat genetic resource conservation. ( view less ) Martine Périgny,Isabelle Bairati,Isabelle Harvey,Michel Beauchemin,François Harel,Marie Plante,Bernard Têtu Matrix metalloproteinases (MMPs) are enzymes thought to be involved in tumor invasion. We hypothesized that MMP-2 and MMP-11 overexpression was associated with the aggressiveness of ovarian carcinoma. This study was performed on samples from 100 patients with stage III ovarian carcinomas treated su... ( view more )rgically between 1990 and 2000. Immunohistochemical staining was performed on ovarian tumors and peritoneal implants using monoclonal antibodies. Overexpression was defined as more than 10% of cells expressing the marker. Multivariate analyses showed that only MMP-2 overexpression by cancer cells in peritoneal implants was associated with a significant risk of death by disease (hazard ratio, 2.65; 95% confidence interval, 1.41-4.97; P =.003). MMP-11 overexpression was not predictive of survival. These results suggest that MMP-2 overexpression by cancer cells in peritoneal implants and not in the primary ovarian cancer is predictive of ovarian cancer prognosis and more likely reflects the presence of particularly aggressive clones of cancer cells. ( view less ) Isabelle Bonnin,Michel Rousset,Delphine Madur,Pierre Sourdille,Céline Dupuits,Dominique Brunel,Isabelle Goldringer The transition from vegetative to floral meristems in higher plants is determined by the coincidence of internal and environmental signals. Contrary to the photoperiod pathway, convergent evolution of the cold-dependent pathway has implicated different genes between dicots and monocots. Whereas no ... ( view more )association between natural variation in vernalization requirement and Flowering time locus T (FT) gene polymorphism has been described in Arabidopsis, recent studies in Triticeae suggest implication of orthologous copies of FT in the cold response. In our study, we show that nucleotide polymorphisms on A and D copies of the wheat FT gene were associated with variations for heading date in a collection of 239 lines representing diverse geographical origins and status (landraces, old or recent cultivars). Interestingly, polymorphisms in the non-coding intronic region were strongly associated to flowering variation observed on plants grown without vernalization. But differently from VRN1, no epistatic interaction between FT homeologous copies was revealed. In agreement with the results of association study, the A and D copies of FT were mapped in regions including major QTLs for earliness traits in hexaploid wheat. This work, by identifying additional homeoalleles involved in wheat vernalization pathway, will contribute to a better understanding of the control of flowering, hence providing tools for the breeding of varieties with enhanced adaptation to changing environments. ( view less )
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