Overall and cause-specific mortality in GH-deficient adults on GH replacement.

OBJECTIVE: Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients. DESIGN: In KIMS (Pfizer International Metabolic Database) 13,983 GH-deficient patients with 69,056 patient-years of follow-up were available. METHODS: This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P<0.05. RESULTS: All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04-1.24). Significant associations were female gender, younger age at follow-up, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (P=0.017) and malignancies (P=0.044). CONCLUSIONS: GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.

Eficiência do politungstato de sódio no fracionamento densimétrico da matéria orgânica do solo

Soluções de iodeto de sódio (NaI) e de politungstato de sódio (PTS) têm sido utilizadas, de forma indistinta, no fracionamento densimétrico da matéria orgânica (MO) do solo. O objetivo deste estudo foi avaliar o efeito desses dois produtos em soluções de mesma densidade (1,80 kg L-1), bem como do aumento da densidade da solução de PTS (2,0 e 2,2 kg L-1), na obtenção de C na fração leve (FL) da MO do solo. As características estruturais da FL obtida com as diferentes soluções também foram avaliadas por ressonância magnética nuclear do 13C (RMN-13C) neste estudo, o qual foi realizado com amostras da camada de 0-5 cm de dois solos brasileiros (PVd-Argissolo Vermelho e LVd-Latossolo Vermelho). A dispersão do solo foi realizada com ultra-som (250 J mL-1 no PVd e 450 J mL-1 no LVd); a suspensão de 20 g de solo e 80 mL-1 de solução foi centrifugada (2.000 g, 90 min), e a FL, obtida pela filtragem do sobrenadante em filtro de fibra de vidro, sendo o C desta fração analisado por combustão seca (Shimadzu TOC-V CSH). O uso da solução de PTS aumentou a recuperação de C da FL em 152 % no PVd e em 166 % no LVd, em comparação à solução de NaI de mesma densidade (1,8 kg L-1). O incremento da densidade da solução de PTS também aumentou a obtenção de C na FL, o qual foi mais expressivo na densidade de 1,8 para 2,0 kg L-1 (57 % em ambos os solos) do que de 2,0 para 2,2 kg L-1 (21 % no PVd e 5 % no LVd). Com base nos teores de Fe e C da fração argila, estimou-se que a contaminação da FL com C da fração argila, quando do uso das soluções de PTS, variou de 1,9 a 3,5 % no LVd e de 6,8 a 10,4 % no PVd, os quais foram considerados baixos perante o alto percentual de incremento na recuperação de C na FL. O incremento da razão C Alquil/C-O-alquil e do C-carbonila na análise de RMN-13C sugere incremento na recuperação de FL em estádios mais avançados de decomposição com o uso de PTS e incremento da densidade da solução, tendo sido esses resultados mais expressivos no LVd. Com base no incremento da obtenção de C e na baixa contaminação da FL com C da fração argila, recomenda-se o uso da solução de PTS 2,0 kg L-1 em estudos de fracionamento densimétrico da MO do solo.

Tandem repeat sequence variation as causative cis-eQTLs for protein-coding gene expression variation: the case of CSTB.

Association studies have revealed expression quantitative trait loci (eQTLs) for a large number of genes. However, the causative variants that regulate gene expression levels are generally unknown. We hypothesized that copy-number variation of sequence repeats contribute to the expression variation of some genes. Our laboratory has previously identified that the rare expansion of a repeat c.-174CGGGGCGGGGCG in the promoter region of the CSTB gene causes a silencing of the gene, resulting in progressive myoclonus epilepsy. Here, we genotyped the repeat length and quantified CSTB expression by quantitative real-time polymerase chain reaction in 173 lymphoblastoid cell lines (LCLs) and fibroblast samples from the GenCord collection. The majority of alleles contain either two or three copies of this repeat. Independent analysis revealed that the c.-174CGGGGCGGGGCG repeat length is strongly associated with CSTB expression (P = 3.14 × 10(-11)) in LCLs only. Examination of both genotyped and imputed single-nucleotide polymorphisms (SNPs) within 2 Mb of CSTB revealed that the dodecamer repeat represents the strongest cis-eQTL for CSTB in LCLs. We conclude that the common two or three copy variation is likely the causative cis-eQTL for CSTB expression variation. More broadly, we propose that polymorphic tandem repeats may represent the causative variation of a fraction of cis-eQTLs in the genome.

Transition et rétablissement

Cet article présente les risques liés aux transitians de soins et en particulier hospitalo-ambulatoires, qui, sans mesure d'accompagnement proactive, menacent le processus de rétablissement des personnes souffrant de troubles psychiatriques. En effet, les risques de rupture des soins et de réadmission sont davantage liés aux caractéristiques du système sociosanitaire qu'à celles du patient ou de la maladie. Des mesures d'accompagnement simples ne sont pas systématiques dans le domaine de la psychiatrie, alors même que ces patients sont particulièrement vulnérables dans les périodes de post-hospitalisation souvent synonymes de barrières au traitement. Le modèle de case management de transition développé à Lausanne est brièvement présenté et illustré au moyen d'une vignette clinique. Ses particularités sont notamment le recours systématique à certains outils soutenant le rétablissement et l'implication active du patient et de son entourage depuis l'hospitalisation jusqu'au retour dans la communauté.

Whole-body 3D T1-weighted MR imaging in patients with prostate cancer: feasibility and evaluation in screening for metastatic disease.

PURPOSE: To develop and assess the diagnostic performance of a three-dimensional (3D) whole-body T1-weighted magnetic resonance (MR) imaging pulse sequence at 3.0 T for bone and node staging in patients with prostate cancer. MATERIALS AND METHODS This prospective study was approved by the institutional ethics committee; informed consent was obtained from all patients. Thirty patients with prostate cancer at high risk for metastases underwent whole-body 3D T1-weighted imaging in addition to the routine MR imaging protocol for node and/or bone metastasis screening, which included coronal two-dimensional (2D) whole-body T1-weighted MR imaging, sagittal proton-density fat-saturated (PDFS) imaging of the spine, and whole-body diffusion-weighted MR imaging. Two observers read the 2D and 3D images separately in a blinded manner for bone and node screening. Images were read in random order. The consensus review of MR images and the findings at prospective clinical and MR imaging follow-up at 6 months were used as the standard of reference. The interobserver agreement and diagnostic performance of each sequence were assessed on per-patient and per-lesion bases. RESULTS: The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were significantly higher with whole-body 3D T1-weighted imaging than with whole-body 2D T1-weighted imaging regardless of the reference region (bone or fat) and lesion location (bone or node) (P < .003 for all). For node metastasis, diagnostic performance (area under the receiver operating characteristic curve) was higher for whole-body 3D T1-weighted imaging (per-patient analysis; observer 1: P < .001 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P = .006 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging; observer 2: P = .006 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P = .006 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging), as was sensitivity (per-lesion analysis; observer 1: P < .001 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P < .001 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging; observer 2: P < .001 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P < .001 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging). CONCLUSION: Whole-body MR imaging is feasible with a 3D T1-weighted sequence and provides better SNR and CNR compared with 2D sequences, with a diagnostic performance that is as good or better for the detection of bone metastases and better for the detection of lymph node metastases.

High-precision U-Pb and 40Ar/39Ar dating of an Alpine ophiolite (Gets nappe, French Alps)

Coarse-grained gabbros from two different localities in the Gets nappe (Upper Prealps) have been dated by U-Pb and Ar-40/Ar-39 isotopic analyses. Zircons from both gabbros gave identical concordant U-Pb ages of 166 +/- 1 Ma (Fig. 4). Amphibole from one of them gave an Ar-40/Ar-39 plateau age of 165.9 +/- 2.2 Ma (Fig. 5). This concordance implies that 166 +/- 1 Ma is the age of magmatic crystallization of these gabbros. The Gets wildflysch with its mafic and ultramafic lenses is an ophiolitic melange, that we infer to come from a proximal part of the accretionary prism at the foot of the active SE margin of the Piemont ocean. In this position we can expect to find remnants of the oldest parts of the Piemont oceanic crust. These are the first high-precision dates using modern techniques from an Alpine ophiolite and are in excellent agreement with the following: 1) The few, somewhat younger, reliable ages on ophiolites from the probable continuation of the Piemont basin into the Apennines and Corsica; 2) Recent data on the age of the first supra-ophiolitic sediments (Late Bathonian to Early Callovian radiolarites); 3) The structural and stratigraphic evolution of the Brianconnais (s.s.) domain, the future NW margin of the Piemont ocean. We note a remarkable coincidence, in Late Bajocian time, between: (A) the end of tensile fracturing in the Brianconnais continental crust; (B) the beginning of its subsidence; (C) the age of the Gets ophiolites. This coincidence is consistent with an ocean opening mechanism based on a combination of subhorizontal extension and thermally driven vertical movements of the lithosphere.

Reliure de : Le Théâtre d'agriculture et mesnage des champs, d'Olivier de Serres...

Numérisation partielle de reliure

Biomassa e estoque de carbono e nutrientes em florestas montanas da mata atlântica na região norte do estado do Rio de Janeiro

Os estudos sobre balanço de C e nutrientes em florestas naturais permitem avaliar possíveis alterações decorrentes de técnicas de manejo aplicadas e possibilitam inferir a sustentabilidade dessas florestas. Os objetivos deste trabalho foram avaliar o teor de nutrientes de espécies nativas e quantificar a biomassa (parte aérea + serapilheira) e os estoques de C e nutrientes em fragmentos florestais montanos da Mata Atlântica (Floresta Ombrófila Densa Montana) na região norte do Estado do Rio de Janeiro, no período de maio de 1999 a abril de 2001. Foram selecionados dois fragmentos, localizados a 900 e 600 m de altitude, na vertente atlântica do Parque Estadual do Desengano, RJ. O solo de ambos os fragmentos florestais foi classificado como Cambissolo Háplico Tb distrófico. O valor médio de biomassa (parte aérea + serapilheira) foi de 166,8 Mg ha-1. Em consequência, a acumulação média de C na vegetação foi de 67, 2 Mg ha-1. Os estoques médios de N, P, K, Ca e Mg na vegetação foram de 1.152, 44,4, 276,5, 603,5 e 127,9 kg ha-1, respectivamente. Por outro lado, as espécies revelaram distinta capacidade de estoque de nutrientes. O balanço negativo de P, K e Ca {solo - (parte aérea + serapilheira)} indica que esses elementos constituem principais fatores nutricionais limitantes ao crescimento dos fragmentos florestais montanos da Mata Atlântica na região norte-fluminense.

Genome-wide arrays in routine diagnostics of hematological malignancies.

Over the last three decades, cytogenetic analysis of malignancies has become an integral part of disease evaluation and prediction of prognosis or responsiveness to therapy. In most diagnostic laboratories, conventional karyotyping, in conjunction with targeted fluorescence in situ hybridization analysis, is routinely performed to detect recurrent aberrations with prognostic implications. However, the genetic complexity of cancer cells requires a sensitive genome-wide analysis, enabling the detection of small genomic changes in a mixed cell population, as well as of regions of homozygosity. The advent of comprehensive high-resolution genomic tools, such as molecular karyotyping using comparative genomic hybridization or single-nucleotide polymorphism microarrays, has overcome many of the limitations of traditional cytogenetic techniques and has been used to study complex genomic lesions in, for example, leukemia. The clinical impact of the genomic copy-number and copy-neutral alterations identified by microarray technologies is growing rapidly and genome-wide array analysis is evolving into a diagnostic tool, to better identify high-risk patients and predict patients' outcomes from their genomic profiles. Here, we review the added clinical value of an array-based genome-wide screen in leukemia, and discuss the technical challenges and an interpretation workflow in applying arrays in the acquired cytogenetic diagnostic setting.

Collaboration entre cliniciens et chercheurs autour de la "consultation systémique": double regard sur un cas clinique

Cet article vise à montrer comment chercheurs et cliniciens peuvent collaborer et s'enrichir mutuellement en utilisant la «consultation systémique», en deux séances, dont le but est l'évaluation des interactions familiales, avec mise en lumière des ressources comme des difficultés de la famille. Lors d'une première rencontre, les questions qui motivent les parents et/ou le(s) thérapeute(s) à consulter sont formulées et la famille est invitée à faire des jeux familiaux semi-standardisés qui sont filmés. Lors d'une deuxième rencontre réunissant les mêmes personnes, un visionnement d'extraits des films sert de base aux réponses des chercheurs et à une discussion commune. Une vignette clinique, concernant des violences intrafamiliales, illustrera la richesse et l'utilité de ces consultations et montrera qu'une collaboration entre chercheurs et cliniciens est fructueuse pour toutes les parties concernées.

[Illustrations de Description de l'Académie royale des Arts de peinture et de sculpture] / [Non identifié] ; Nicolas Guérin, aut. du texte

Comprend : [ Planche dépliante entre pp. 64-65. ] Elévation des faces des murs du Salon de l'Académie [royale des Arts de peinture et de sculpture. XVIIIè siècle.] [ Cote : BNF C 107129. ] ; [ Planche dépliante entre pp.104-105. ] Plan et élévation de la salle où se tiennent ordinairement les Assemblés. [ Académie royale des Arts de peinture et de sculpture. XVIIIè siècle.] [ Cote : BNF C 107130. ] ; [ Planche dépliante entre pp.164-166. ] Plan et élévation de la troisième salle de l'Académie [royale des Arts de peinture et de sculpture] où sont les vases de Medicis. [XVIIIè siècle.] [ Cote : BNF C 106592. ] ; [ Planche dépliante entre pp.208-209. ] Plan de la salle séparée des autres. [ Une salle de l'Académie royale des Arts de peinture et de sculpture. XVIIIè siècle.] [ Cote : BNF C 107131. ] ; [ Planche dépliante entre pp. 246-247. ] Plan du vestibule par où on entre dans le salon [de l'Académie royale des Arts de peinture et de sculpture. XVIIIè siècle.] [ Cote : BNF C 107132. ] ; [ Planche dépliante entre pp.256-257. ] Plan de l'Ecole du modèle [ à l'Académie royale des Arts de peinture et de sculpture. XVIIIè siècle.] [ Cote : BNF C 107133. ]

Identification of Novel Craniofacial Regulatory Domains Located far Upstream of SOX9 and Disrupted in Pierre Robin Sequence.

Mutations in the coding sequence of SOX9 cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions, and duplications within a ∼2 Mb region upstream of SOX9 can recapitulate the CD-DSD phenotype fully or partially, suggesting the existence of an unusually large cis-regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus for isolated PRS at ∼1.2-1.5 Mb upstream of SOX9 has been previously reported. The craniofacial regulatory potential within this locus, and within the greater genomic domain surrounding SOX9, remains poorly defined. We report two novel deletions upstream of SOX9 in families with PRS, allowing refinement of the regions harboring candidate craniofacial regulatory elements. In parallel, ChIP-Seq for p300 binding sites in mouse craniofacial tissue led to the identification of several novel craniofacial enhancers at the SOX9 locus, which were validated in transgenic reporter mice and zebrafish. Notably, some of the functionally validated elements fall within the PRS deletions. These studies suggest that multiple noncoding elements contribute to the craniofacial regulation of SOX9 expression, and that their disruption results in PRS.