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2.
Nanotechnology ; 34(1)2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36126589

RESUMO

Hexagonal SiGe-2H has been recently shown to have a direct bandgap, and holds the promise to be compatible with silicon technology. Hexagonal Si and Ge have been grown on an epitaxial lattice matched template consisting of wurtzite GaP and GaAs, respectively. Here, we present the growth of hexagonal Si and SiGe nanowire branches grown from a wurtzite stem by the vapor-liquid-solid growth mode, which is substantiated byin situtransmission electron microscopy. We show that the composition can be tuned through the whole range of stoichiometry from Si to Ge, and the possibility to realize Si and SiGe heterostructures in these branches.

3.
Eur Ann Otorhinolaryngol Head Neck Dis ; 139(2): 61-64, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34175252

RESUMO

OBJECTIVES: The present study aimed to determine normal SNR values per age group for the 50% speech reception threshold in noise (SNR Loss) on the VRB (Vocale Rapide dans le Bruit: rapid speech in noise) test. MATERIAL AND METHODS: Two hundred patients underwent pure-tone threshold and VRB speech-in-noise audiometry. Six ages groups were distinguished: 20-30, 30-40, 40-50, 50-60, 60-70 and>70 years. All subjects had normal hearing for age according to ISO 7029. SNR Loss was measured according to age group. RESULTS: Mean SNR Loss ranged from -0.37dB in the youngest age group (20-30 years) to +6.84dB in the oldest (>70 years). Range and interquartile range increased with age: 3.66 and 1.49dB respectively for 20-30 year-olds; 6 and 3.5dB for>70 year-olds. Linear regression between SNR Loss and age showed a coefficient R2 of 0.83. CONCLUSION: The present study reports SNR Loss values per age group in normal-hearing subjects (ISO 7029), confirming that SNR Loss increases with age. Scatter also increased with age, suggesting that other age-related factors combine with inner-ear aging to impair hearing in noise.


Assuntos
Percepção da Fala , Adulto , Idoso , Audiometria de Tons Puros , Audiometria da Fala , Limiar Auditivo , Audição , Humanos , Ruído/efeitos adversos , Adulto Jovem
4.
Eur Ann Otorhinolaryngol Head Neck Dis ; 139(1): 21-27, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34140263

RESUMO

OBJECTIVES: This document presents the fundamentals of speech audiometry in noise, general requirements for implementation and criteria for choice among the tests available in French according to the health-professional's needs. MATERIAL AND METHODS: The recommendations are based on a systematic analysis of the literature carried out by a multidisciplinary group of doctors, audiologists and audioprosthetists from all over France. They are graded A, B, C or expert opinion according to decreasing level of scientific evidence. RESULTS: Eight tests of speech audiometry in noise can be used in France. CONCLUSION: To be complete, evaluation of hearing status requires testing understanding of speech in noise. The examination must begin with a minimum of two measurements familiarizing the subject with the test procedure. For initial diagnosis, adaptive procedures establishing the 50% speech reception threshold (SRT50) in noise are to be preferred in order to obtain a rapid and standardized measurement of perception of speech in noise. When the aim is to measure real-life speech comprehension, tests based on sentences, cocktail-party noise and free-field stimulation are to be preferred. Prosthetic gain is evaluated exclusively in free field. This is the only way to evaluate the contribution of binaurality and to measure perception in noise in an environment as close as possible to real life. In order to avoid acoustic interference in free field, at least five loudspeakers should be used, in particular for evaluating the effectiveness of directional microphones, CROS devices enabling sounds picked up in the damaged ear to be rerouted to the functional ear, or bimodal fitting (i.e., when hearing is enabled by two modalities: for example, hearing aid for one ear, cochlear implant for the other).


Assuntos
Audiologia , Implantes Cocleares , Auxiliares de Audição , Otolaringologia , Percepção da Fala , Adulto , Humanos , Fala
6.
Eur Ann Otorhinolaryngol Head Neck Dis ; 137(1): 21-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31582332

RESUMO

AIM: To evaluate azimuthal sound-source localization performance under different conditions, with a view to optimizing a routine sound localization protocol. MATERIAL AND METHOD: Two groups of healthy, normal-hearing subjects were tested identically, except that one had to keep their head still while the other was allowed to turn it. Sound localization was tested without and then with a right ear plug (acute auditory asymmetry) for each of the following sound stimuli: pulsed narrow-band centered on 250Hz, continuous narrowband centered on 2000Hz, 4000Hz and 8000Hz, continuous 4000Hz warble, pulsed white noise, and word ("lac" (lake)). Root mean square error was used to calculate sound-source localization accuracy. RESULTS: With fixed head, localization was significantly disturbed by the earplug for all stimuli (P<0.05). The most discriminating stimulus was continuous 4000Hz narrow-band: area under the ROC curve (AUC), 0.99 [95% CI, 0.95-1.01] for screening and 0.85 [0.82-0.89] for diagnosis. With mobile head, localization was significantly better than with fixed head for 4000 and 8000Hz stimuli (P<0.05). The most discriminating stimulus was continuous 2000Hz narrow-band: AUC, 0.90 [0.83-0.97] for screening and 0.75 [0.71-0.79] for diagnosis. In both conditions, pulsed noise (250Hz narrow-band, white noise or word) was less difficult to localize than continuous noise. CONCLUSION: The test was more sensitive with the head immobile. Continuous narrow-band stimulation centered on 4000Hz most effectively explored interaural level difference. Pulsed narrow-band stimulation centered on 250Hz most effectively explored interaural time difference. Testing with mobile head, closer to real-life conditions, was most effective with continuous narrow-band stimulation centered on 2000Hz.


Assuntos
Estimulação Acústica , Localização de Som/fisiologia , Adulto , Feminino , Testes Auditivos , Humanos , Masculino , Valores de Referência , Adulto Jovem
7.
J Pediatr Urol ; 15(5): 555.e1-555.e5, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31324475

RESUMO

INTRODUCTION: Although ureteral length (UL) is highly variable in children, reliable data on this topic are scarce. During urinary tract surgery, the use of an inappropriately dimensioned ureteral stent is associated with adverse effects. This study aimed to evaluate UL as a function of the child's age, using contrast-enhanced computed tomography (CT) of the abdomen and pelvis, and to calculate a new equation for predicting UL (and thus the optimal length of ureteral stents) in children. MATERIAL AND METHODS: A retrospective, single-centre study of children (younger than 16 years) who are free of abdominal mass syndrome and severe scoliosis was conducted. After three-dimensional reconstruction of the CT data, the ureter was measured between the ureteropelvic junction and ureterovesical junction by two observers. The lengths of the right and left ureters were analyzed by age, with at least 10 CT measurements per age class. RESULTS: The mean ULs on the right and left were, respectively, 9.7 and 9.91 cm before the age of 1 year, 20.10 and 21.08 cm at the age of 7 and 26.55 and 27.46 cm at the age of 16. The interobserver reproducibility of UL determination was high (intraclass correlation coefficient [95% confidence interval]: 0.97 [0.94-0.99]). On the basis of these results, the length of the double-J catheter should be equal to the child's age +12 cm (Table 1). CONCLUSION: Computed tomography measurement of the UL in healthy children is reproducible and reliable and enabled the estimation of the UL by age group. This knowledge should facilitate the choice of the stent used in ureteral surgery. To confirm the study results, the stent size suggested here should be evaluated in routine practice.


Assuntos
Imageamento Tridimensional/métodos , Pelve Renal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Ureter/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Tamanho do Órgão , Reprodutibilidade dos Testes , Estudos Retrospectivos , Urografia/métodos
9.
Eur Ann Otorhinolaryngol Head Neck Dis ; 135(5): 315-319, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30072287

RESUMO

INTRODUCTION: Understanding speech in noise is a major challenge for most hearing-impaired subjects, with or without hearing aids. To overcome the weaknesses of French-language speech-in-noise tests, we developed a new instrument, with a balanced mix of difficulty of the speech material. MATERIAL AND METHODS: The speech material comprised 127 sentences taken from the "Marginal Benefit from Acoustic Amplification" (MBAA) corpus, each including 3 keywords. The noise was created using the "onde vocale globale" (global vocal wave: OVG), described by Dodelé. The 127 speech/noise pairs were recorded individually after root-mean-square equalization. The first experiment, on 10 normal-hearing adults, determined the signal-to-noise ratio (SNR) associated with 50% correct keyword identification in each sentence (SNR-50), using an ascending method with noise level set at 73dB SPL. Relative levels between sentences and noise were then adjusted sentence by sentence to achieve an SNR-50 of 0dB. The second experiment, with 12 normal-hearing adults, validated the equalization of sentence difficulty. RESULTS: Mean SNR-50 was -6.64dB (σ=1.47). Mean adjusted SNR-50 was 0.08dB (σ=0.55). Mean psychometric curve slope was 19.3%/dB, with low standard deviations, testifying to the sensitivity of the speech material. CONCLUSION: The VRB (vocale rapide dans le bruit: rapid speech in noise) test is based on sentences from the MBAA corpus with background noise based on the OVG at different signal-to-noise ratios. The test is feasible and able to detect slight variations in speech-in-noise performance between subjects.


Assuntos
Audiometria da Fala/métodos , Ruído , Percepção da Fala , Adulto , Feminino , Humanos , Masculino , Psicometria , Razão Sinal-Ruído , Adulto Jovem
10.
Eur Ann Otorhinolaryngol Head Neck Dis ; 135(4): 259-264, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29731298

RESUMO

Sound source localization is paramount for comfort of life, determining the position of a sound source in 3 dimensions: azimuth, height and distance. It is based on 3 types of cue: 2 binaural (interaural time difference and interaural level difference) and 1 monaural spectral cue (head-related transfer function). These are complementary and vary according to the acoustic characteristics of the incident sound. The objective of this report is to update the current state of knowledge on the physical basis of spatial sound localization.


Assuntos
Localização de Som/fisiologia , Humanos , Fenômenos Físicos
11.
Nanotechnology ; 29(12): 125601, 2018 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-29328052

RESUMO

We report on an unprecedented formation of allotrope heterostructured Si nanowires by plastic deformation based on applied radial compressive stresses inside a surrounding matrix. Si nanowires with a standard diamond structure (3C) undergo a phase transformation toward the hexagonal 2H-allotrope. The transformation is thermally activated above 500 °C and is clearly driven by a shear-stress relief occurring in parallel shear bands lying on {115} planes. We have studied the influence of temperature and axial orientation of nanowires. The observations are consistent with a martensitic phase transformation, but the finding leads to clear evidence of a different mechanism of deformation-induced phase transformation in Si nanowires with respect to their bulk counterpart. Our process provides a route to study shear-driven phase transformation at the nanoscale in Si.

12.
Clin Biochem ; 51: 103-109, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28941591

RESUMO

Immunoglobulin E (IgE) gammopathy is a rare disorder, accounting for just 0.1% of all patients with multiple myeloma (MM). Herein, we report a case of IgE monoclonal gammopathy without any biological and clinical symptoms, and we review 63 published cases in the literature. Demographic, biological and clinical presentations and features appear to be similar to those of other subtypes of MM, with a median age of diagnosis of 67years. There is a slight excess of male patients, and incidence seems to increase with age. The prevalence of renal failure, anaemia and hypercalcaemia at diagnosis was computed to be at 26%, 44% and 18%, respectively, in patients with MM. According to the literature, IgE MM is more aggressive and associated with poorer survival. Nonetheless, cases that are prolonged have also been described.


Assuntos
Imunoglobulina E/sangue , Paraproteinemias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletroforese Capilar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
J R Army Med Corps ; 163(6): 397-400, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28495951

RESUMO

INTRODUCTION: During military deployment, the diagnosis and the management of acute bacterial meningitis can be problematic, as deployed Medical Treatment Facilities (MTFs) often have a limited laboratory diagnostic capability. However, French Role 2 and 3 MTFs have point-of-care (POC) testing to perform urinary (Multistix 10 SG strip) and blood (iSTAT handheld analyser) biochemical testing mentioned in AMedP8.5. The purpose of this study was to compare the accuracy of this urine test strip and of the iSTAT CHEM8 and CG4 cartridges with a standard hospital bench top analyser in order to determine if these POC devices have a potential role in the biochemical analysis of cerebrospinal fluid (CSF protein, CSF glucose and CSF lactate, respectively). METHODS: Agreement between the index methods and the reference methods (suitable kits on the Cobas 6 000 System) was evaluated by parallel testing of 30 CSF samples by both techniques. For CSF protein, agreement between the strip and the reference method was evaluated determining the κ coefficient. For CSF glucose and CSF lactate subgroups, least squares linear regressions were calculated and Bland-Altman analyses were performed. RESULTS: The Multistix 10 SG strip can be used to make a semiquantitative determination of CSF protein. A good agreement between the strip and the reference method was observed (κ coefficient: 0.93 (IC95 0.82 to 1)). This strip is thus well adapted to demonstrate an elevation of CSF protein level as observed in acute bacterial meningitis. The iSTAT CHEM8 and CG4+ cartridges correlated well with the reference methods for the determination of CSF glucose and CSF lactate, respectively (r2>0.98) but exhibited a negative bias (∼ -7% and ∼ -15%, respectively). CONCLUSIONS: The combined use of the Multistix 10 SG strip and of the iSTAT system appears to be an attractive solution for the biochemical investigation of CSF in medical treatment facilities with limited laboratory diagnostic capability.


Assuntos
Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/diagnóstico , Testes Imediatos , Fitas Reagentes , Biomarcadores/líquido cefalorraquidiano , Líquido Cefalorraquidiano/química , Proteínas do Líquido Cefalorraquidiano/química , Glucose/análise , Humanos , Ácido Láctico/análise
14.
Bone Marrow Transplant ; 51(5): 698-704, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26808568

RESUMO

There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ⩽120 ng/mL versus 43% with concentration >120 ng/mL (P<0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ⩾10(-3) and in those with MRD <10(-3) before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.


Assuntos
Ciclosporina/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pré-Medicação/métodos , Adolescente , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Intervalo Livre de Doença , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Lactente , Leucemia Mieloide Aguda/mortalidade , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Risco , Taxa de Sobrevida , Doadores de Tecidos , Adulto Jovem
15.
Ann Pharm Fr ; 73(3): 180-9, 2015 May.
Artigo em Francês | MEDLINE | ID: mdl-25592653

RESUMO

A product of the arms race during the Cold War, the Russian VX, or VR, is an organophosphorus compound that is a structural isomer of the western VX compound (or A4), with which it shares a very high toxicity. It is much less studied and known than VX because the knowledge of its existence is relatively recent. A very low volatility and high resistance in the environment make it a persistent agent. Poisoning occurs mainly following penetration through skin and mucosa but vapour inhalation is a credible risk in some circumstances. The clinical presentation may be differed by several hours and despite the absence of signs and symptoms, the casualty should not be considered as contamination or intoxication-free. This agent has a long residence time in blood, a characteristics that clearly differentiates it from other compounds such as sarin. The protocols for antidote administration may thus have to be changed accordingly. The fact that VR poisoned individuals will less respond to the current oxime therapy used in France, the 2-PAM and that VR represents a higher threat than VX, being probably possessed by some proliferating states, justify the interest for this toxic product.


Assuntos
Agentes Neurotóxicos/toxicidade , Compostos Organotiofosforados/toxicidade , Animais , Inibidores da Colinesterase/química , Inibidores da Colinesterase/toxicidade , Humanos , Agentes Neurotóxicos/química , Compostos Organotiofosforados/química , Intoxicação/terapia , Federação Russa
16.
PLoS One ; 9(11): e111813, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25368990

RESUMO

Identification of conserved co-expression networks is a useful tool for clustering groups of genes enriched for common molecular or cellular functions [1]. The relative importance of genes within networks can frequently be inferred by the degree of connectivity, with those displaying high connectivity being significantly more likely to be associated with specific molecular functions [2]. Previously we utilized cross-species network analysis to identify two network modules that were significantly associated with distant metastasis free survival in breast cancer. Here, we validate one of the highly connected genes as a metastasis associated gene. Tpx2, the most highly connected gene within a proliferation network specifically prognostic for estrogen receptor positive (ER+) breast cancers, enhances metastatic disease, but in a tumor autonomous, proliferation-independent manner. Histologic analysis suggests instead that variation of TPX2 levels within disseminated tumor cells may influence the transition between dormant to actively proliferating cells in the secondary site. These results support the co-expression network approach for identification of new metastasis-associated genes to provide new information regarding the etiology of breast cancer progression and metastatic disease.


Assuntos
Neoplasias da Mama/genética , Redes Reguladoras de Genes , Neoplasias Pulmonares/genética , Animais , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Transplante de Neoplasias , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Prognóstico , Transcriptoma , Carga Tumoral
17.
J Clin Endocrinol Metab ; 99(12): 4740-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25222755

RESUMO

CONTEXT: Recent data indicate that the secreted glycoprotein sclerostin may be involved in vascular calcification (VC). OBJECTIVE: The objective of the study was to establish whether serum sclerostin levels are associated with VC in patients with rheumatoid arthritis (RA). DESIGN: This was a cross-sectional study. SETTING: The study was conducted with ambulatory care. PATIENTS: We compared 75 RA patients with 75 age- and gender-matched control participants. INTERVENTION: Coronary artery calcification (CAC) and abdominal aortic calcification (AAC) scores were evaluated by computed tomography. MAIN OUTCOME MEASURE: Serum sclerostin levels (determined with an ELISA) were assessed. A statistical analysis was performed to identify the determinants of serum sclerostin and VC. RESULTS: AAC and CAC were more prevalent and more severe in patients with RA than in controls. Higher levels of AAC (P = .02) and a higher lumbar bone mineral density (BMD; P = .03) were identified as independent determinants of higher serum sclerostin levels in RA patients, whereas male gender (P = .03), higher lumbar BMD (P < .0001), and low estimated glomerular rate (P < .001) were identified as determinants in controls. In RA patients, a multivariate logistic regression analysis indicated that older age [P < .01, with an odds ratio (OR) per year 1.10] and male gender (P = .02, OR 6.79) were independent determinants of CAC and that older age (P < .001, OR 1.16) were independent determinants of AAC. In controls, the independent determinants were older age (P < .01, OR 1.19), hypertension (P < .01, OR 7.31), and lumbar BMD (P = .03, OR per 30 mg/cm(2) increment of 1.14) for CAC and older age (P = .01, OR 1.11) for AAC. CONCLUSIONS: Serum sclerostin levels were significantly and independently associated with AAC in RA patients.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/patologia , Densidade Óssea , Proteínas Morfogenéticas Ósseas/sangue , Calcificação Vascular/patologia , Absorciometria de Fóton , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Artrite Reumatoide/complicações , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Calcificação Vascular/etiologia
18.
J Agric Food Chem ; 62(40): 9841-7, 2014 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-25213754

RESUMO

Fruits contain polyphenols, widespread antioxidants beneficial for human health. Their mass transfer was studied during the leaching of apple slices immersed in mannitol solutions with ranging concentrations (0, 0.2, 0.4, and 0.6 M). The solution of Fick's law for unsteady mass transfer in planar configuration was used to calculate apparent diffusivity (De). Polyphenols were quantified by high-performance liquid chromatography for each immersion time. Leaching from raw apple tissues occurred only when cell integrity was lost, here at a certain level of difference in osmotic pressure. Different diffusivity values were found in the two apple varieties. Values of De either decreased from 0.2 to 0.1 × 10(-9) and 0.2 × 10(-9) m(2) s(-1) for Golden Delicious and Granny Smith, respectively, or were not determined when the mannitol concentration increased from 0 to 0.6 M. The osmotic strength of the solution strongly impacted the leaching rate of polyphenols from apple cells. The structure of the polyphenols also affected De, with low values for procyanidins.


Assuntos
Malus/química , Polifenóis/química , Carboidratos/análise , Carboidratos/química , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Cumáricos/química , Difusão , Flavonoides/química , Cinética , Manitol/química , Pressão Osmótica , Polifenóis/análise , Proantocianidinas/química , Soluções
19.
Arch Pediatr ; 21(10): 1101-5, 2014 Oct.
Artigo em Francês | MEDLINE | ID: mdl-25125033

RESUMO

In adults, lacidipine seems to have no CYP3A4-inhibiting action. This particular characteristic makes it advantageous when combined with drugs metabolized by CYP3A4, such as cyclosporine. Until now, no data on the efficacy or safety of this calcium antagonist have been available in children. Thirty-nine hypertensive children (age: 0.13-14 years) receiving lacidipine in oncohematology for a mean of 75 days were included in this retrospective study. The causes of high blood pressure were renal tumor (n=7), catecholamine-secreting tumor (n=4), corticoid treatment (n=5), and cyclosporine treatment (n=23). An initial dosage of 0.05 mg/kg/day was sufficient for 41% of the patients. The remaining patients needed to increase the dosage, by steps of 0.03 mg/kg/day, until reaching an average effective dosage of 0.1 mg/kg/day. Lacidipine significantly decreased blood pressure by 30 (±14) mmHg for systolic blood pressure and by 26 (±13) mmHg for diastolic blood pressure. A medication plan with twice-daily administration was not significantly more effective than a single administration per day. Lacidipine was well tolerated, and no toxicity-related withdrawal of treatment occurred. For 22 patients treated with both cyclosporine and lacidipine, renal function was not disturbed over time, suggesting its preservation by lacidipine. No significant increase in cyclosporine blood concentration was detected. Lacidipine seems to be an effective calcium antagonist in pediatric oncohematology, is well tolerated, has a kidney-protector effect and no drug interaction when combined with cyclosporine.


Assuntos
Anti-Hipertensivos/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Ciclosporina/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Taxa de Filtração Glomerular , Glucocorticoides/efeitos adversos , Humanos , Hipertensão/etiologia , Imunossupressores/efeitos adversos , Lactente , Masculino , Neoplasias/complicações , Estudos Retrospectivos
20.
Genome Res ; 24(2): 227-40, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24322557

RESUMO

Metastasis is the result of stochastic genomic and epigenetic events leading to gene expression profiles that drive tumor dissemination. Here we exploit the principle that metastatic propensity is modified by the genetic background to generate prognostic gene expression signatures that illuminate regulators of metastasis. We also identify multiple microRNAs whose germline variation is causally linked to tumor progression and metastasis. We employ network analysis of global gene expression profiles in tumors derived from a panel of recombinant inbred mice to identify a network of co-expressed genes centered on Cnot2 that predicts metastasis-free survival. Modulating Cnot2 expression changes tumor cell metastatic potential in vivo, supporting a functional role for Cnot2 in metastasis. Small RNA sequencing of the same tumor set revealed a negative correlation between expression of the Mir216/217 cluster and tumor progression. Expression quantitative trait locus analysis (eQTL) identified cis-eQTLs at the Mir216/217 locus, indicating that differences in expression may be inherited. Ectopic expression of Mir216/217 in tumor cells suppressed metastasis in vivo. Finally, small RNA sequencing and mRNA expression profiling data were integrated to reveal that miR-3470a/b target a high proportion of network transcripts. In vivo analysis of Mir3470a/b demonstrated that both promote metastasis. Moreover, Mir3470b is a likely regulator of the Cnot2 network as its overexpression down-regulated expression of network hub genes and enhanced metastasis in vivo, phenocopying Cnot2 knockdown. The resulting data from this strategy identify Cnot2 as a novel regulator of metastasis and demonstrate the power of our systems-level approach in identifying modifiers of metastasis.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Metástase Neoplásica/genética , Neoplasias/genética , Proteínas Repressoras/genética , Animais , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Camundongos , MicroRNAs/genética , Metástase Neoplásica/patologia , Neoplasias/patologia , Locos de Características Quantitativas/genética , RNA Mensageiro/genética
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