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1.
Tijdschr Psychiatr ; 63(11): 796-803, 2021.
Artigo em Holandês | MEDLINE | ID: mdl-34851519

RESUMO

BACKGROUND: The Dutch Personality Inventory for DSM-5 (PID-5-NL) is the APA recommended questionnaire to assess maladaptive personality traits as defined in the Alternative DSM-5 model of personality disorders. AIM: To describe of the psychometric qualities of the PID-5-NL, present of normative data and apply the PID-5-NL in clinical practice. METHOD: The PID-5-NL was administered in a sample of adults from the general population in Flanders (Belgium) and in a sample of patients with a personality disorder in mental health care in the Netherlands. Scores on the PID-5 of a patient with borderline personality disorder are illustrated in a case vignette. RESULTS: Reliability and validity of the PID-5-NL were satisfactory to good, and comparable with results from international research on the PID-5. It was remarkable that in the current research group, patients scored as low as or even lower than the group from the general population on a number of trait facets. CONCLUSION: The PID-5-NL questionnaire is a useful tool to gain insight in a straightforward way into a wide range of relevant personality traits for diagnosis and treatment planning; provisional reference groups for the clinical practice in regular mental health care are made available on the basis of this study. Further refinement of the reference groups and further research within patients with externalizing personality problems is recommended.


Assuntos
Psicometria , Adulto , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Países Baixos , Inventário de Personalidade , Reprodutibilidade dos Testes
2.
Heredity (Edinb) ; 122(1): 53-68, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29720718

RESUMO

Understanding how dispersal and gene flow link geographically separated the populations over evolutionary history is challenging, particularly in migratory marine species. In southern right whales (SRWs, Eubalaena australis), patterns of genetic diversity are likely influenced by the glacial climate cycle and recent history of whaling. Here we use a dataset of mitochondrial DNA (mtDNA) sequences (n = 1327) and nuclear markers (17 microsatellite loci, n = 222) from major wintering grounds to investigate circumpolar population structure, historical demography and effective population size. Analyses of nuclear genetic variation identify two population clusters that correspond to the South Atlantic and Indo-Pacific ocean basins that have similar effective breeder estimates. In contrast, all wintering grounds show significant differentiation for mtDNA, but no sex-biased dispersal was detected using the microsatellite genotypes. An approximate Bayesian computation (ABC) approach with microsatellite markers compared the scenarios with gene flow through time, or isolation and secondary contact between ocean basins, while modelling declines in abundance linked to whaling. Secondary-contact scenarios yield the highest posterior probabilities, implying that populations in different ocean basins were largely isolated and came into secondary contact within the last 25,000 years, but the role of whaling in changes in genetic diversity and gene flow over recent generations could not be resolved. We hypothesise that these findings are driven by factors that promote isolation, such as female philopatry, and factors that could promote dispersal, such as oceanographic changes. These findings highlight the application of ABC approaches to infer the connectivity in mobile species with complex population histories and, currently, low levels of differentiation.


Assuntos
Evolução Molecular , Variação Genética/genética , Genética Populacional , Baleias/genética , Animais , Clima , DNA Mitocondrial/genética , Fluxo Gênico/genética , Genótipo , Haplótipos/genética , Repetições de Microssatélites/genética , Oceano Pacífico , Filogenia , Densidade Demográfica , Baleias/fisiologia
3.
Tumour Biol ; 36(10): 7699-710, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25934335

RESUMO

Hypoxia is a characteristic feature of solid tumors leading to the over expression of hypoxia-inducible factor (HIF)-1α protein and therefore to a specific cellular behavior. However, even though the oxygen tension in tumors is low (<5 %), most of the cell lines used in cancer studies are grown under 21 % oxygen tension. This work focuses on the impact of oxygen conditions during in vitro cell culture on glucose metabolism using 1-(13)C-glucose. Growing U87-MG glioma cells under hypoxic conditions leads to a two- to threefold reduction of labeled glutamine and an accumulation of fructose. However, under both hypoxic and normoxic conditions, glucose is used for de novo synthesis of pyrimidine since the (13)C label is found both in the uracil and ribose moieties. Labeling of the ribose ring demonstrates that U87-MG glioma cells use the reversible branch of the non-oxidative pentose phosphate pathway. Interestingly, stereotactic implantation of U87-MG cells grown under normoxia or mild hypoxia within the striatum of nude mice led to differential growth; the cells grown under hypoxia retaining an imprint of the oxygen adaptation as their development is then slowed down.


Assuntos
Glioblastoma/metabolismo , Glioblastoma/patologia , Glucose/metabolismo , Hipóxia/metabolismo , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Hipóxia/patologia , Camundongos , Camundongos Nus , Oxigênio/metabolismo
4.
Acta Chir Belg ; 115(5): 334-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26559999

RESUMO

BACKGROUND: The operating theatre (OT) is a complex environment. The purpose of this survey was to evaluate the implementation of the surgical checklist (SC) at individual level by Belgian Surgeons. METHODS: A Surgical Checklist Questionnaire (SCQ) related to the use of the SC by individual surgeons was attached to the registration website for the 2015 Belgian Surgical Week. It was a one page long, user friendly document, easy to be filled voluntarily and anonymously. RESULTS: Among the 206 surgeons who registered, 81 (39%) filled in the SCQ. The SC template proposed by the WHO "Safe Surgery Saves Lives" initiative was used by 91% of the respondents. However, 89% adapted the SC to their local hospital environment, and 87.5% use it personally for their patients. Since implementation, the SC was never adapted in 46%. According to 21% of respondents, an adverse event was avoided thanks to the SC. Amazingly, SC was considered as an administrative burden by 83% despite the same percentage recognized that patients benefited from the SC. Only 28% of respondents got feedback from the use of the SC. CONCLUSIONS: In this survey, the number of adverse event avoided thanks to the use of the SC demonstrates that SC -represents a simple strategy for addressing surgical patient safety in OT. Nevertheless, SC is still considered by many surgeons as an additional administrative burden and/or as just another gimmick. Further studies are needed to understand why some surgeons are still not willing to adapt to a changing safety culture.


Assuntos
Lista de Checagem , Segurança do Paciente , Padrões de Prática Médica , Especialidades Cirúrgicas , Adulto , Idoso , Atitude do Pessoal de Saúde , Bélgica , Feminino , Humanos , Masculino , Erros Médicos/prevenção & controle , Pessoa de Meia-Idade , Inquéritos e Questionários
5.
Med Phys ; 37(2): 877-84, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20229897

RESUMO

PURPOSE: Susceptibility effects are a very efficient source of contrast in magnetic resonance imaging. However, detection is hampered by the fact the induced contrast is negative. In this work, the SIgnal Response MApping (SIRMA) to dephaser method is proposed to map susceptibility gradient to improve visualization. METHODS: In conventional gradient echo acquisitions, the echo formation of susceptibility affected spins is shifted in k-space, the shift being proportional to the susceptibility gradient. Susceptibility gradients map can be produced by measuring this induced shifts. The SIRMA method measures these shifts from a series of dephased images collected with additional incremental dephasers. These additional dephasers correspond either to a slice refocusing gradient offset or to a reconstruction window off-centering. The signal intensity profile as a function of the additional dephaser was determined on a pixel-by-pixel basis from the ensemble of dephased images. Susceptibility affected voxels presented a signal response profile maximum shifted compared to nonaffected voxels ones. Shift magnitude and sign were measured for each pixel to determine susceptibility gradients and produce a susceptibility gradient map. RESULTS: In vitro experiments demonstrated the ability of the method to map gradient inhomogeneities induced by a cylinder. Quantization accuracy was evaluated comparing SIRMA images and simulations performed on the well-characterized air filled cylinder model. Performances of the SIRMA method, evaluated in vitro on cylinders filled with various superparamagnetic iron oxide SPIO concentrations, showed limited influence of acquisition parameters. Robustness of the method was then assessed in vivo after an infusion of SPIO-loaded nanocapsules into the rat brain using a convection-enhanced drug delivery approach. The region of massive susceptibility gradient induced by the SPIO-loaded nanocapsules was clearly delineated on SIRMA maps and images were compared to T2* weighted images, Susceptibility Gradient Map (SGM), and histological Perl's staining slice. The potential for quantitative evaluation of SPIO distribution volume was demonstrated. CONCLUSIONS: The proposed method is a promising technique for a wide range of applications especially in molecular or cellular imaging with respect to its quantitative nature and its computational simplicity.


Assuntos
Algoritmos , Encéfalo/anatomia & histologia , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Animais , Feminino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
6.
Br J Anaesth ; 100(2): 195-202, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18211993

RESUMO

BACKGROUND: Little research has been performed on designing appointment systems for the preoperative assessment clinic (PAC). We aimed to investigate how two organizational planning difficulties, (i) long access times and (ii) long waiting times, could be analysed systematically. METHODS: Two simulation models were used to test different scenarios to reduce access time and waiting times. First, we determined the number of appointments needed to reduce the access time from 5 weeks to 10 working days for 95% of all patients. Subsequently, we determined how long the consultation time should be, taking patients' American Society Anesthesiologists (ASA) physical status into account, to reduce the maximum waiting time to 10 min for 95% of all patients. RESULTS: Although we found the actual capacity, that is, consultations per day, to be enough to meet demand, a backlog existed, as the access time for the PAC was 5 weeks. A temporary extra capacity is needed to eliminate this backlog. When the reserved consultation time is 18 min for patients with ASA class I or II and 30 min for patients with ASA class III or IV, the maximum waiting times decrease to 10 min for 95% of all patients. CONCLUSIONS: This study shows that a simulation model is a helpful tool to determine the capacity needed to achieve and to maintain a proposed service level for access times and waiting times. In addition, waiting times at the PAC can be reduced by making the reserved consultation time dependent on patients' ASA physical status.


Assuntos
Agendamento de Consultas , Simulação por Computador , Modelos Organizacionais , Ambulatório Hospitalar/organização & administração , Cuidados Pré-Operatórios/métodos , Acessibilidade aos Serviços de Saúde , Pesquisa sobre Serviços de Saúde/métodos , Humanos , Países Baixos , Fatores de Tempo , Listas de Espera
7.
Br J Anaesth ; 100(3): 322-6, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18238838

RESUMO

BACKGROUND: The quality of the preoperative assessment clinic (PAC) is determined by many factors. Patients' experiences are important indicators, but often overlooked. We prepare to set priorities to improve the PAC by obtaining detailed patients' feedback on the quality of the PAC, and establishing the value patients and professionals attach to different care aspects, using the Patient Experiences with the Preoperative Assessment Clinic questionnaire. METHODS: The PAC's standard of service was determined for five care aspects (dimensions), using patients' feedback. The importance of a dimension to patients was determined by calculating the effects of the dimensions on patients' overall appraisal. In addition, professionals were asked to rate the importance of the different care aspects. RESULTS: Patients had the most positive experiences with the nurse, and the least positive experiences with waiting. However, waiting was least important to patients. When combining the PAC's standard of service with the value given to the dimensions by patients and professionals separately, we found in both instances that waiting was in greatest need of improvement. This was followed by reception, the anaesthetist, remaining experiences, and finally the nurse. CONCLUSIONS: Quality improvement of the PAC can be achieved by obtaining patients' feedback on the quality, determine a PAC's standard of service, recognize service areas that require improvement, and identify actions appropriate to bring about improvement. The value patients and professionals attach to different aspects of care can then be used to prioritize improvements.


Assuntos
Anestesiologia/normas , Ambulatório Hospitalar/normas , Satisfação do Paciente , Cuidados Pré-Operatórios/normas , Qualidade da Assistência à Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Feminino , Prioridades em Saúde , Pesquisa sobre Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Inquéritos e Questionários
8.
Eur J Anaesthesiol ; 25(4): 280-6, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18177541

RESUMO

BACKGROUND AND OBJECTIVE: Previous research has shown that a preoperative assessment clinic enhances hospital cost-efficiency. However, the differences in organization of the patient flow have not been analysed. In this descriptive study, we evaluated the consequences of the organization of the patient flow of a preoperative assessment clinic on its performance, by analysing two Dutch university hospitals, which are organized essentially differently. METHODS: In the final analysis, the study included 880 patients who visited either academic centre. The performance of the two preoperative assessment clinics was evaluated by measuring patient flow time, various procedure times and the total waiting time. Patients' age, ASA physical status and any preoperative tests requested by the physician were also recorded. RESULTS: There was a significant difference in patient flow time between the two preoperative assessment clinics. More time was needed for the preoperative assessment when patients' ASA class was higher. The patient flow time was longer when electrocardiogram and venepuncture were performed at the general outpatient laboratory than when they were performed at the preoperative assessment clinic due to longer waiting times. More tests were requested when they were performed at the preoperative assessment clinic. CONCLUSIONS: This study shows that the organization of patient flow is an important aspect of the logistic processes of the preoperative assessment clinic. It might influence patient flow times as well as the number of preoperative tests requested. Together with other aspects of logistic performance, patient satisfaction and quality of medical assessment, patient flow logistics can be used to assess the quality of a preoperative assessment clinic.


Assuntos
Agendamento de Consultas , Eficiência Organizacional , Ambulatório Hospitalar/organização & administração , Cuidados Pré-Operatórios/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Indicadores Básicos de Saúde , Hospitais Universitários/organização & administração , Hospitais Universitários/normas , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Países Baixos , Ambulatório Hospitalar/normas , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Fatores de Risco , Fatores de Tempo
9.
Br J Anaesth ; 99(5): 666-72, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17875566

RESUMO

BACKGROUND: Presently, no comprehensive and validated questionnaire to measure patient experiences of the preoperative assessment clinic (PAC) is available. We developed and validated the Patient Experiences with the Preoperative Assessment Clinic (PEPAC) questionnaire, which can be used for quantitative measurements of patient experiences of the PAC. METHODS: We adapted the National Health Service outpatient questionnaire, incorporating questions specific for anaesthesiology. To make the PEPAC appropriate for quantitative measurements, dimensions and single items suitable for statistical analysis were constructed. Each dimension consists of multiple items measuring the same aspect of care. Reliability was established by computing Cronbach's alpha coefficients. Construct validity was assessed by correlating the dimensions with the patient's overall appraisal (Pearson's r). These dimensions should explain a substantial level of variance of the patients' overall appraisal; therefore, regression analysis was performed. RESULTS: After a pilot phase, the questionnaire was sent to 700 consecutive patients (response 74%). Five scales measuring five dimensions of patient experiences were constructed. Cronbach's alpha ranged from 0.56 to 0.84, supporting reliability of the PEPAC. Correlations between the dimensions and patients' overall appraisal ranged from 0.22 to 0.56. Collectively, the five scales explained 51% of patients' overall appraisal. CONCLUSIONS: The PEPAC is a comprehensive, reliable, and validated questionnaire to measure patient experiences with the PAC. It might be a useful tool to identify the service areas of the PAC that require improvement and to determine which actions can bring about improvement.


Assuntos
Anestesiologia/normas , Ambulatório Hospitalar/normas , Satisfação do Paciente , Cuidados Pré-Operatórios/normas , Inquéritos e Questionários/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Cuidados Pré-Operatórios/psicologia , Psicometria , Reprodutibilidade dos Testes
10.
J Clin Oncol ; 10(11): 1795-801, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1403060

RESUMO

PURPOSE: A prospective clinical study was performed to determine the incidence of high-dose continuous intravenous infusion fluorouracil (5FU-CIV) cardiotoxicity. PATIENTS AND METHODS: Three hundred sixty-seven patients who were given first-cycle high-dose 5FU-CIV were monitored for cardiac function by clinical examination, ECG, and laboratory tests. 5FU-CIV was administered during a 96- or 120-hour period at doses that ranged from 600 to 1,000 mg/m2/d. Associated drugs included cisplatin (56%), mitomycin (12.5%), folinic acid (leucovorin) (7%), and others (14%). Thirty-nine patients (10.5%) received 5FU as a single agent. RESULTS: 5FU-induced cardiac events occurred in 28 patients (7.6%; 95% confidence interval, 4.9% to 10.3%). Nine of them had a history of cardiac disease. Primary tumors included head and neck (n = 13), gastrointestinal (n = 6), breast (n = 3), and others (n = 6). The mean onset time of cardiac symptoms was 3 days (range, 2 to 5). Inaugural symptoms included angina pectoris (n = 18), hypotension (n = 6), hypertension (n = 5), malaise (n = 4), dyspnea (n = 2), arrhythmia (n = 1), or sudden death (n = 1). At 5FU discontinuation, six patients' cardiac symptoms returned to baseline, but 21 patients experienced unstable angina (n = 8), hypotension/cardiovascular collapse (n = 11), pulmonary edema (n = 1), or sudden death (n = 4). The lethality rate was 2.2% (five sudden deaths plus three irreversible collapses). ECG showed repolarization changes (ST segment deviation; T-wave inversion) in 65% and/or diffuse microvoltage in 22% of the patients who presented with cardiac events. Echocardiography showed partial or global hypokinesia in nine of the 16 patients who were examined, and one case of prolonged akinesia. Cardiac enzymes rarely showed an increase (n = 2). In severe but reversible cases, clinical, ECG, and echographic parameters returned to baseline status within 48 hours after the drug discontinuation. A fluorine 19 nuclear magnetic resonance (19F NMR) analysis of urine was performed on 14 patients; six had cardiac symptoms and eight did not. Fluoroacetate (FAC), a known cardiotoxic compound, was detected in all cases. CONCLUSION: In our study, the incidence of high-dose 5FU-CVI cardiotoxicity was 7.6%. The hypothesis of a toxic cardiomyopathic process requires further confirmation.


Assuntos
Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Cardiopatias/induzido quimicamente , Adulto , Idoso , Ecocardiografia , Eletrocardiografia , Feminino , Fluoracetatos/urina , Cardiopatias/diagnóstico por imagem , Cardiopatias/fisiopatologia , Humanos , Infusões Intravenosas , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Estudos Prospectivos
11.
Mech Dev ; 67(1): 3-16, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9347911

RESUMO

We review the early stages of chick embryogenesis, in particular the formation of the hypoblast, and the ingression of endoderm and mesoderm through the primitive streak. The formation of a trilaminar embryo during gastrulation is accompanied by the specification of body axes. The first axis is already present in the unfertilized egg and runs from the cytoplasmatic animal to the yolk rich vegetal pole. Already within the uterus a second axis conveys bilateral symmetry to the embryo. It extends from a dorsal/anterior to a ventral/posterior position. These axial poles segregate during gastrulation to form the classical coordinates, a dorsal-ventral and an anterior-posterior axis. The establishment of axes is accompanied by the expression of specific combinations of homeobox genes during gastrulation in the chick, as in other metazoa. We review the avian specific information and compare it with findings in other species. A combinatorial homeobox code for the specification of identities during development is discussed.


Assuntos
Proteínas Aviárias , Embrião de Galinha/fisiologia , Gástrula/fisiologia , Genes Homeobox , Animais , Padronização Corporal/genética , Endoderma , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Mesoderma , Proteínas do Tecido Nervoso/genética , Fatores de Transcrição Otx , Transativadores/genética , Fatores de Transcrição/genética
12.
Mech Dev ; 92(1): 47-54, 2000 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-10704887

RESUMO

Despite the pivotal role of the pancreas in hormonally-regulated pathways in the body, e.g. glucose homeostasis, the genetic mechanisms defining it have for many years remained largely enigmatic. After years out of the spotlight, pancreas development has once again come to centre stage. To a large extent, this is due to recent advances made through the detailed analysis of transgenic mice which have been engineered to carry mutations in specific developmental control genes. This review specifically focuses on the specification of the endocrine pancreas lineage and in particular on the role of the developmental control genes Pax4 and Pax6 in the generation of specific endocrine cell types. The comparison of various phenotypes of different mouse mutants affecting endocrine development supports a model in which Pax4 and Pax6 are required for the differentiation of certain endocrine cell lineages and implies a potential for acting at different levels of endocrine development.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Proteínas de Homeodomínio/fisiologia , Pâncreas/citologia , Pâncreas/embriologia , Fatores de Transcrição/fisiologia , Animais , Diferenciação Celular , Proteínas de Ligação a DNA/genética , Proteínas do Olho , Proteínas de Homeodomínio/genética , Camundongos , Camundongos Knockout , Modelos Biológicos , Família Multigênica , Mutação , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados , Proteínas Repressoras , Fatores de Transcrição/genética
13.
Mech Dev ; 55(1): 91-108, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8734502

RESUMO

Up to now around 170 different homeobox genes have been cloned from vertebrate genomes. A compilation of the various isolates from mouse, chick, frog, fish and man is presented in the form of a concise checklist, including the designations from the original publications. Putative homologs from different species are aligned, and key characteristics of embryonic or adult expression domains, as well as mutant phenotypes are briefly indicated.


Assuntos
Genes Homeobox , Animais , Humanos , Vertebrados/genética
14.
Anat Embryol (Berl) ; 209(4): 263-7, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15864642

RESUMO

Glomerular differentiation starts as soon as embryonic stage 12 in mice and suggests that kidneys may be functional at this stage. Dynamic contrast-enhanced magnetic resonance microscopy, a noninvasive imaging technique, was used to assess renal function establishment in utero. Indeed, in adults (n = 3), an intravenous injection of gadolinium-DOTA induced in a first step a massive and rapid drop in kidney signal intensity followed, in a second step, by a drop in bladder signal intensity. The delay in signal changes between kidney and bladder reflected glomerular filtration. Pregnant mice underwent anatomical and dynamic contrast-enhanced magnetic resonance microscopy on postcoital days 12-13 (n = 2), 13-14 (n = 1), 14-15 (n = 3), 15-16 (n = 2), 16-17 (n = 3), 17-18 (n = 3), and 18-19 (n = 1). Kidneys and bladder were unambiguously depicted prior to contrast agent injection on stage 15-16 embryos. Contrast agent injection allowed kidney, detection as early as stage 12-13 but not bladder. Kinetics of signal changes demonstrated that glomerular filtration is established at embryonic stage 15-16 in mice. Thus, anatomical and dynamic contrast-enhanced magnetic resonance microscopy may be a powerful noninvasive method for in vivo prenatal developmental and functional studies.


Assuntos
Glomérulos Renais/embriologia , Glomérulos Renais/fisiologia , Imageamento por Ressonância Magnética/métodos , Animais , Diferenciação Celular , Meios de Contraste/administração & dosagem , Feminino , Compostos Heterocíclicos/administração & dosagem , Cinética , Camundongos , Microscopia/métodos , Compostos Organometálicos/administração & dosagem , Bexiga Urinária/embriologia
15.
FEBS Lett ; 363(1-2): 25-8, 1995 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-7729546

RESUMO

The gene encoding murine p68 RNA helicase (Hlr1) was mapped to the distal portion of mouse chromosome 11 by linkage analysis of DNA restriction length polymorphisms using an interspecific genetic backcross between (C57BL/6J x SPRET/Ei) F1 hybrids and SPRET/Ei mice. A closely related gene (Hlr1-ps1) was identified, isolated, and mapped to the proximal part of the same chromosome. Sequence analysis and PCR results suggest that Hlr1-ps1 is a pseudogene, flanked by DNA stretches similar to mouse insertion element IE118.


Assuntos
Mapeamento Cromossômico , RNA Nucleotidiltransferases/genética , Animais , Sequência de Bases , Cruzamentos Genéticos , DNA/química , Desoxirribonuclease EcoRI , Ligação Genética , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , RNA Helicases , Análise de Sequência de DNA
16.
Invest Radiol ; 38(3): 141-6, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12595793

RESUMO

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate superparamagnetic iron oxide (SPIO) nanoparticles to discriminate infarcted from normal tissue after myocardial infarction using high field MR imaging (7 tesla). MATERIALS AND METHODS: Permanent myocardial infarction was induced in rats. SPIO nanoparticles (1 mg Fe/kg) were assessed with T1-weighted gradient echo sequence to visualize the myocardial infarction 48 hours after ligature (n = 6). Furthermore, MR Imaging was performed using a T2-weighted RARE sequence and nanoparticles were injected (5 or 10 mg Fe/kg) on 36 rats 5, 24 or 48 hours after infarction. RESULTS: No changes in contrast between normal and infarcted myocardium was observed after nanoparticle injection on T1-weighted images. However, nanoparticles induced a significant contrast increase between normal and infarcted myocardium on T2-weighted images whatever the delay between infarction and imaging (2.99 +/- 1.66 preinjection vs. 7.82 +/- 1.96 after SPIO injection at a dose of 5 mg Fe/kg 5 hours postinfarction, P = 0.0001). CONCLUSIONS: Nanoparticle injection made it possible to discriminate normal from infarcted myocardium on T2-weighted images. However, the high magnetic field prevented the visualization of the T1 effect of SPIO nanoparticles.


Assuntos
Ferro , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/diagnóstico , Óxidos , Análise de Variância , Animais , Feminino , Modelos Animais , Nanotecnologia , Tamanho da Partícula , Ratos , Ratos Wistar
17.
Invest Radiol ; 35(3): 180-5, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10719827

RESUMO

RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the diagnostic use of MRI and, more precisely, the use of quantitative T2 imaging at 7 T for the early detection of neuronal cerebral alterations after transient ischemia in the gerbil. METHODS: One hundred forty-seven Mongolian gerbils were separated into four groups for which a bicarotid artery occlusion lasted for 4, 6, 8, or 10 minutes, respectively. The animals were scanned before carotid artery occlusion and at 3, 6, 10, 24, and 48 hours and 5 days after the ischemic incident. MR images were acquired on a Bruker Avance DRX300 mini-imaging system. RESULTS: Our results show that T2 mapping is able to localize brain damage induced by transient ischemia and to detect early perturbations in water content (as early as 6 hours after ischemia). CONCLUSIONS: T2 measurements in the striata are correlated with the severity of the ischemic incident, since the changes observed on the T2 images are directly proportional to the duration of occlusion.


Assuntos
Modelos Animais de Doenças , Ataque Isquêmico Transitório/patologia , Imageamento por Ressonância Magnética , Animais , Gerbillinae
18.
DNA Cell Biol ; 14(11): 971-81, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7576184

RESUMO

Using oligonucleotides complementary to the conserved inter-finger region of a variety of previously described zinc finger-encoding genes, a novel mouse gene was cloned and characterized. The gene is localized on chromosome 8 and comprises five exons. Its corresponding mRNA is developmentally regulated in various tissues and includes an open reading frame encoding a protein of 72,422 daltons. It shares amino-terminal homologies with human KRAB (or FPB) boxes, and contains 13 zinc fingers of the C2-H2 type. The NK10 KRAB domains exhibit repressing activity when tested in GAL4 fusion protein assays. Cloning of putative target sequences revealed that the individual domains differentially contribute to zinc-dependent target DNA binding.


Assuntos
Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Repressoras/genética , Dedos de Zinco , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Sequência de Bases , Mapeamento Cromossômico , Clonagem Molecular , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/biossíntese , Éxons/genética , Humanos , Camundongos , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Especificidade de Órgãos , RNA Mensageiro/biossíntese , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Repressoras/análise , Proteínas Repressoras/biossíntese , Análise de Sequência de DNA
19.
Cancer Chemother Pharmacol ; 42(3): 201-9, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9685055

RESUMO

PURPOSE: Fluorine-19 magnetic resonance spectroscopy (19F-M RS) studies of the pharmacokinetics of the anticancer drug 5-fluorouracil (FU) in patients at several clinical centres have shown that increased tumour retention of FU is associated with patient response. The mechanism of this increased tumour retention (FU trapping) is unknown. We used a pre-clinical model to investigate whether other MRS-measurable parameters would correlate with the response to FU treatment and, thus, help elucidate the mechanism(s) involved in FU trapping. METHODS: MRS spectra were obtained using a double-tuned (31P/19F) surface coil from 29 N-methyl-N-nitrosourea-induced primary rat tumours. 31P-MRS spectra were acquired immediately prior to and at 2.5 h post-treatment with a bolus i.p. injection of FU (100 mg/ kg); 19F-MRS spectra were acquired during the intervening 2.5-h period for measurement of the tumour uptake and retention of FU and of its metabolism to the cytotoxic fluoronucleotides (FNuct). From these data, four parameters were measured: tumour pH and energy status (NTP/Pi) before treatment, total FU retention, and FU anabolism to FNuct (expressed as micromoles per gram per 2.5 h). In addition, tumour response was determined at 7 days post-treatment by measurement of the percentage of change in tumour weight and was classified according to standard oncological criteria as follows: progressive (P) for a > or =25% increase, remissive (R) for a > or =50% decrease or stable (S) for values lying between these two. RESULTS: Analysis of variance (ANOVA) for statistical assessment revealed that groups P, S and R were not distinguishable using the MRS parameters; although when S and R were combined as one group of non-progressive disease (NPD; n = 24), both the NTP/Pi ratio and the total FNuct formed were significantly greater (P = 0.04) than those observed in the P group (n = 5). Considering all 29 tumours, linear regression showed that there were positive significant correlations between the NTP/Pi ratio and (a) the percentage of response (P = 0.04), (b) the pre-treatment pH (P = 0.002) and (c) FU retention (P = 0.02), but not FNuct formation (P = 0.66). Unlike results reported in the clinic, the percentage of response and FU retention were neither significantly correlated (P = 0.22) nor associated when groups P and NPD were compared (P = 0.27, Fischer's exact test). FNuct, however, was significantly associated with response, as was the NTP/Pi ratio (P < or = 0.02). Combination of FNuct with the NTP/Pi ratio increased the significance of the association with response (P = 0.003, Fischer's exact test). CONCLUSIONS: Our results indicate that in this particular model the pre-treatment tumour NTP/Pi ratio was the best predictor of response to a bolus injection of FU, rather than FNuct formation or FU retention. An elevated NTP/Pi ratio could reflect a well-vascularised tumour with an improved capacity for energy-dependent FU uptake and metabolism to FNuct, suggesting that further investigation of this parameter could be an important line of research, which may aid the identification of tumours likely to be sensitive to FU chemotherapy in the clinic.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Fluoruracila/uso terapêutico , Espectroscopia de Ressonância Magnética/métodos , Neoplasias Experimentais/tratamento farmacológico , Análise de Variância , Animais , Antimetabólitos Antineoplásicos/metabolismo , Antimetabólitos Antineoplásicos/farmacocinética , Carcinógenos , Metabolismo Energético/efeitos dos fármacos , Feminino , Fluoruracila/metabolismo , Fluoruracila/farmacocinética , Metilnitrosoureia , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar
20.
Brain Res ; 879(1-2): 193-9, 2000 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-11011022

RESUMO

The olfactory bulbectomized (OB) rat is a well-accepted animal model of depression. The present magnetic resonance imaging (MRI) investigation demonstrates alterations in signal intensities in cortical, hippocampal, caudate and amygdaloid regions in OB animals, but not in sham operated controls. Ventricular enlargement was also evident in OB animals. These alterations have implications with regard to the face and construct validity of this model.


Assuntos
Encéfalo/fisiopatologia , Depressão/fisiopatologia , Bulbo Olfatório/fisiologia , Tonsila do Cerebelo/fisiologia , Tonsila do Cerebelo/fisiopatologia , Animais , Encéfalo/fisiologia , Núcleo Caudado/fisiologia , Núcleo Caudado/fisiopatologia , Córtex Cerebral/fisiologia , Córtex Cerebral/fisiopatologia , Ventrículos Cerebrais/fisiologia , Ventrículos Cerebrais/fisiopatologia , Modelos Animais de Doenças , Hipocampo/fisiologia , Hipocampo/fisiopatologia , Imageamento por Ressonância Magnética , Ratos , Valores de Referência
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