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1.
Phys Rev Lett ; 120(22): 225902, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29906135

RESUMO

Experiments on self-diffusion in amorphous silicon (Si) were performed at temperatures between 460 to 600° C. The amorphous structure was prepared by Si ion implantation of single crystalline Si isotope multilayers epitaxially grown on a silicon-on-insulator wafer. The Si isotope profiles before and after annealing were determined by means of secondary ion mass spectrometry. Isothermal diffusion experiments reveal that structural relaxation does not cause any significant intermixing of the isotope interfaces whereas self-diffusion is significant before the structure recrystallizes. The temperature dependence of self-diffusion is described by an Arrhenius law with an activation enthalpy Q=(2.70±0.11) eV and preexponential factor D_{0}=(5.5_{-3.7}^{+11.1})×10^{-2} cm^{2} s^{-1}. Remarkably, Q equals the activation enthalpy of hydrogen diffusion in amorphous Si, the migration of bond defects determining boron diffusion, and the activation enthalpy of solid phase epitaxial recrystallization reported in the literature. This close agreement provides strong evidence that self-diffusion is mediated by local bond rearrangements rather than by the migration of extended defects as suggested by Strauß et al. (Phys. Rev. Lett. 116, 025901 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.025901).

2.
Arq. bras. med. vet. zootec ; 66(4): 1039-1045, 08/2014. tab
Artigo em Português | LILACS | ID: lil-722585

RESUMO

Este estudo objetivou avaliar e comparar a glicose e o lactato plasmáticos, bem como a insulina e o cortisol séricos, em éguas hígidas, não gestantes, tratadas com: polietilenoglicol 3350 (PEG); ou polietilenoglicol 3350 associado ao Ringer lactato (PEG+RL); ou solução isotônica poliônica enteral (SIPE); ou solução isotônica poliônica enteral associada ao Ringer lactato (SIPE+RL); ou solução de cloreto de sódio a 0,9 por cento (NaCl). A avaliação laboratorial foi realizada nos tempos: imediatamente antes do início dos tratamentos (T0h); com seis horas (T6h) e ao final dos tratamentos (T12h); com 24 (T24h) e 48 horas (T48h) após T0h. Não ocorreu alteração significativa no lactato plasmático. Ocorreu apenas um discreto aumento nos valores da glicose e da insulina no tratamento SIPE, ocasionado pela presença de maltodextrina. O cortisol aumentou nos animais de todos os tratamentos, porém menor nos animais do SIPE. Conclui-se que os tratamentos não alteraram os valores da glicose, do lactato e da insulina em éguas hígidas e que a hidratação enteral em fluxo contínuo realizada no tratamento SIPE ocasionou menos estresse nos animais...


The aim of this study was to evaluate and compare the plasmatic lactate and glucose, serum insulin and cortisol in healthy non pregnant mares treated with: polyethylene glycol 3350 (PEG); or polyethylene glycol 3350 associated with Ringer lactate (PEG+RL), or enteral polionic isotonic solution (EPIS); or enteral polionic isotonic solution associated with Ringer lactate (EPIS+RL); or sodium chloride solution 0.9 percent (NaCl). Laboratory tests were carried out in the following moments: immediately before the start of treatment (T0h), at six hours (T6h) and at the end of treatment (T12h), with 24 (T24h) and 48 hours (T48h) after T0h. The lactate did not change significantly. There was a slight increase in glucose and insulin values in EPIS caused by the presence of maltodextrin. Cortisol increased in animals from all treatments, but this increase was lower in the animals in EPIS. It is concluded that the treatments did not alter the values of glucose, lactate and insulin in healthy mares and the enteral hydration in continuous flow done in the EPIS treatment caused less stress to the animals...


Assuntos
Animais , Feminino , Ácido Láctico/sangue , Cavalos/metabolismo , Cetomacrogol/administração & dosagem , Glicemia/análise , Hidratação/veterinária , Insulina/análise
3.
Stat Med ; 32(19): 3357-72, 2013 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-23553813

RESUMO

Cluster randomized trials (CRTs) are often prone to selection bias despite randomization. Using a simulation study, we investigated the use of propensity score (PS) based methods in estimating treatment effects in CRTs with selection bias when the outcome is quantitative. Of four PS-based methods (adjustment on PS, inverse weighting, stratification, and optimal full matching method), three successfully corrected the bias, as did an approach using classical multivariable regression. However, they showed poorer statistical efficiency than classical methods, with higher standard error for the treatment effect, and type I error much smaller than the 5% nominal level.


Assuntos
Análise por Conglomerados , Pontuação de Propensão , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Viés de Seleção , Idoso , Simulação por Computador , Exercício Físico/fisiologia , Exercício Físico/psicologia , Feminino , Humanos , Masculino , Osteoartrite/fisiopatologia , Osteoartrite/terapia , Dor/prevenção & controle
4.
Arq. bras. med. vet. zootec ; 65(1): 145-148, fev. 2013.
Artigo em Português | LILACS | ID: lil-667549

RESUMO

Relata-se a ocorrência de fratura de fíbula e lesões de ligamento colateral e menisco lateral em um muar, fêmea, de dois anos de idade, provavelmente produzida por um coice na região da articulação femorotibiopatelar do membro pélvico esquerdo. O animal apresentava claudicação de grau 5 desse membro e obteve melhora após bloqueio dos nervos fibular, tibial e safena e da articulação afetada. O exame radiográfico da região acometida revelou fratura do terço proximal da fíbula e, ao exame ultrassonográfico, observaram-se pontos anecoicos no ligamento colateral lateral e menisco.


This is a report of the occurrence of fibula fracture and injuries of the collateral ligament and lateral meniscus in a two year old mule, probably due to a kick in the joint area of the femurtibiopatellar left pelvic limb. The animal presented degree 5 lameness which improved after a nerve block of the affected joint. Radiographic examination of the affected area revealed a fracture on the proximal third of the fibula, and the ultrasound examination showed anechoic points observed in the lateral collateral ligament and meniscus.


Assuntos
Animais , Feminino , Fíbula , Ligamentos , Meniscos Tibiais/anormalidades , Radiografia/veterinária
5.
Z Orthop Unfall ; 150(3): 250-6, 2012 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-22179847

RESUMO

INTRODUCTION: Posterior calcaneal exostosis treatment modalities have given rise to many controversial opinions. After failure of the conservative treatment, surgical bursectomy and resection of the calcaneal exostosis are indicated by many authors. But clinical studies also show a high rate of unsatisfactory results with a relative high incidence of complications. The minimally invasive surgical technique by an endoscopic calcaneoplasty (ECP) could be an option to overcome some of these problems. MATERIAL AND METHOD: Between 1999 und 2010 we operated 164 patients with an age range between 16 and 67 years, 81 males and 83 females. The radiological examination prior to surgery documented in all cases a posterior superior calcaneal exostosis that showed friction to the Achilles tendon. All patients included in the study had no clinical varus of the hind foot, nor cavus deformities. All patients had undergone a trial of conservative treatment for at least 6 months and did not show a positive response. The average follow-up was 46.3 (range: 8-120) months. RESULTS: According to the Ogilvie-Harris score 71 patients presented good and 84 patients excellent results, while 5 patients showed fair results, and 4 patients only poor results. All the post-operative radiographs showed sufficient resection of the calcaneal spur. In 61 patients the preoperative MRI showed a partial rupture of the Achilles tendon close to the insertion side. In no case could we observe a complete tear at the time of follow-up. Only minor postoperative complications were observed. In many patients we could observe a chondral layer at the posterior aspect of the calcaneus. Close to the intersion the Achilles tendon showed also in many patients a chondroide metaplasia. CONCLUSION: ECP is an effective and minimally invasive procedure for the treatment of patients with calcaneal exostosis. After a short learning curve the endoscopic exposure is superior to the open technique, has less morbidity, less operating time, and nearly no complications. Moreover, the pathology can be better differentiated.


Assuntos
Calcâneo/cirurgia , Endoscopia/métodos , Esporão do Calcâneo/cirurgia , Adolescente , Adulto , Idoso , Exostose , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome , Resultado do Tratamento , Adulto Jovem
6.
BMJ ; 343: d5886, 2011 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-21948873

RESUMO

OBJECTIVE: To assess the impact of the 2004 extension of the CONSORT guidelines on the reporting and methodological quality of cluster randomised trials. DESIGN: Methodological review of 300 randomly sampled cluster randomised trials. Two reviewers independently abstracted 14 criteria related to quality of reporting and four methodological criteria specific to cluster randomised trials. We compared manuscripts published before CONSORT (2000-4) with those published after CONSORT (2005-8). We also investigated differences by journal impact factor, type of journal, and trial setting. DATA SOURCES: A validated Medline search strategy. Eligibility criteria for selecting studies Cluster randomised trials published in English language journals, 2000-8. RESULTS: There were significant improvements in five of 14 reporting criteria: identification as cluster randomised; justification for cluster randomisation; reporting whether outcome assessments were blind; reporting the number of clusters randomised; and reporting the number of clusters lost to follow-up. No significant improvements were found in adherence to methodological criteria. Trials conducted in clinical rather than non-clinical settings and studies published in medical journals with higher impact factor or general medical journals were more likely to adhere to recommended reporting and methodological criteria overall, but there was no evidence that improvements after publication of the CONSORT extension for cluster trials were more likely in trials conducted in clinical settings nor in trials published in either general medical journals or in higher impact factor journals. CONCLUSION: The quality of reporting of cluster randomised trials improved in only a few aspects since the publication of the extension of CONSORT for cluster randomised trials, and no improvements at all were observed in essential methodological features. Overall, the adherence to reporting and methodological guidelines for cluster randomised trials remains suboptimal, and further efforts are needed to improve both reporting and methodology.


Assuntos
Guias como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto/normas
7.
Eur J Med Res ; 16(2): 76-8, 2011 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-21463986

RESUMO

OBJECTIVES: Oxidative stress is suggested to play an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). The present study was aimed to compare plasma levels of antioxidants in patients suffering from NASH and healthy controls. METHODS: Plasma levels of the antioxidants α-tocopherol, γ-tocopherol, lutein, zeaxanthin, ß-cryptoxanthin, lycopene, α-carotene ß-carotene were determined in 57 patients with biopsy-proven NASH and 40 healthy controls. RESULTS: Levels of α-tocopherol (22.4 vs. 26.8 nmol/ ml; p<0.01), lutein (0.19 vs. 0.33 nmol/ml; p<0.0001), zeaxanthin (0.04 vs. 0.08 nmol/ml; p<0.0001), lyco?pene (0.15 vs. 0.42 nmol/ml; p<0.0001), α-carotene (0.03 vs. 0.06 nmol/ml; p<0.005) and ß-carotene (0.25 vs. 0.39 nmol/ml; p<0.01) were significantly decreased in NASH patients compared to controls. Age, aminotransferase status (ALT, AST) and BMI were not correlated with the levels of tocopherols or caro?tenoids. CONCLUSIONS: Given the decreased levels supplementation of lipophilic antioxidants might be a rational treatment option for patients with NASH.


Assuntos
Antioxidantes/metabolismo , Carotenoides/sangue , Fígado Gorduroso/sangue , Vitamina E/sangue , Fígado Gorduroso/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia
8.
Pathologe ; 30(5): 407-10, 2009 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-19396442

RESUMO

Testosterone secreting tumours of the adrenal glands are usually adrenal carcinomas or adenomas. Here we report the rare case of an adrenal ganglioneuroma with ectopic Leydig cells, a so-called virilizing adrenal ganglioneuroma. Clinically it is characterized by symptoms of virilization, histologically by the occurrence of a population of eosinophilic cells. In the absence of crystalloids of Reinke this cell population can be identified as Leydig cells based on positive immunohistochemical staining of inhibin and calretinin.


Assuntos
Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/patologia , Ganglioneuroma/metabolismo , Ganglioneuroma/patologia , Testosterona/metabolismo , Virilismo/patologia , Córtex Suprarrenal/patologia , Doenças das Glândulas Suprarrenais/patologia , Doenças das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Idoso , Biomarcadores Tumorais/análise , Calbindina 2 , Coristoma/patologia , Coristoma/cirurgia , Diagnóstico Diferencial , Feminino , Ganglioneuroma/cirurgia , Humanos , Inibinas/análise , Laparoscopia , Células Intersticiais do Testículo , Masculino , Proteína G de Ligação ao Cálcio S100/análise , Tomografia Computadorizada por Raios X
9.
Stat Med ; 27(27): 5578-85, 2008 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-18646266

RESUMO

The cluster randomized cross-over design has been proposed in particular because it prevents an imbalance that may bring into question the internal validity of parallel group cluster trials. We derived a sample size formula for continuous outcomes that takes into account both the intraclass correlation coefficient (representing the clustering effect) and the interperiod correlation (induced by the cross-over design).


Assuntos
Glicemia/análise , Análise por Conglomerados , Quimioterapia Assistida por Computador , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Modelos Estatísticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Tamanho da Amostra , Algoritmos , Estudos Cross-Over , Interpretação Estatística de Dados , Humanos , Unidades de Terapia Intensiva , Fatores de Tempo
10.
Pathologe ; 29(5): 371-4, 2008 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-18584175

RESUMO

We report a case of multifocal urothelial carcinoma in situ of the left ureter with early stromal invasion and concomitant in situ lesions in bladder, prostate and seminal vesicle. After complete topographical mapping of the cystoprostatovesiculectomy specimen the unusual manifestation of urothelial carcinoma in situ in a seminal vesicle turned out to be a tumour spread via the ductus ejaculatorius into the seminal vesicle. DNA sequencing of the tumour suppressor gene TP53 of different tumour lesions revealed identical wild-type sequences.


Assuntos
Carcinoma/patologia , Neoplasias dos Genitais Masculinos/patologia , Glândulas Seminais/patologia , Biópsia , Carcinoma in Situ/patologia , Humanos , Masculino , Invasividade Neoplásica , Neoplasias da Próstata/patologia , Espectrometria de Fluorescência
11.
Stat Med ; 27(10): 1693-702, 2008 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-17960596

RESUMO

It is widely accepted that confidence interval construction has important advantages over significance testing for the presentation of research results, as now facilitated by readily available software. However, for a number of effect measures, procedures are either not available or not satisfactory in samples of small to moderate size. In this paper, we describe a general approach for estimating a difference between effect measures, which can also be used to obtain confidence limits for a risk ratio and a lognormal mean. Numerical evaluation shows that this closed-form procedure outperforms existing methods, including the bootstrap.


Assuntos
Intervalos de Confiança , Interpretação Estatística de Dados , Razão de Chances , Asma/tratamento farmacológico , Simulação por Computador , Humanos , Método de Monte Carlo , Projetos de Pesquisa
12.
Epilepsy Behav ; 10(4): 604-10, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17449331

RESUMO

OBJECTIVE: Epilepsy is a common and often highly stigmatized disorder. Several international organizations indicate a need to assess the stigma that exists and to develop and evaluate interventions to dispel myths about epilepsy. METHODS: A stratified cluster randomized controlled trial evaluated whether an epilepsy education program (intervention) increases knowledge of and positive attitudes about epilepsy in Grade 5 students (ages 9-11). The study also investigated characteristics of the individuals (gender, language spoken at home, familiarity with epilepsy) and schools (Catholic vs public, size of school, and school level socioeconomic status) that affect epilepsy knowledge and attitudes. We assessed epilepsy knowledge and attitudes at baseline and 1 month following the program using a 33-item questionnaire. RESULTS: In total, 24 schools (783 individuals) were cluster randomized. Those in the intervention group had an average 11.8-point increase (95% confidence interval (CI)=11.4-12.5) in knowledge 1 month following the program, compared with the control group increase of 2.2 points (95% CI=1.8-2.6) out of a total of 57 points. For attitudes, the intervention group had a mean increase of 8.15 points (95% CI=4.70-11.60), compared with the control group increase of 1.64 points (95% CI=-0.84-4.42) out of a total of 50 points. The intervention was responsible for 63% of the variation in postprogram epilepsy knowledge and 28% of the variation in postprogram attitudes about epilepsy. CONCLUSIONS: The epilepsy education program was associated with a significant increase in epilepsy knowledge and positive attitudes in the intervention group 1 month later compared with the control group.


Assuntos
Epilepsia , Educação em Saúde/métodos , Adolescente , Criança , Análise por Conglomerados , Interpretação Estatística de Dados , Feminino , Seguimentos , Educação em Saúde/ética , Educação em Saúde/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Ontário , Tamanho da Amostra , Inquéritos e Questionários
14.
Stat Med ; 26(2): 336-51, 2007 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-16538705

RESUMO

The study of twins is widely used for research into genetic and environmental influences on human traits. Study designs in which independent samples of monozygotic and dizygotic twins are compared with respect to their similarity have focused on single binary trait. However, the risk of co-occurrence of more than one disease in twins is a parameter of interest to genetic epidemiologists and other investigators. For example, they may be interested in assessing the genetic and environmental etiologies of reading deficits (RD) and attention deficit hyperactivity disorder (ADHD) and their co-morbidity. In this paper, we present statistical methodology for the estimation of twin similarity with respect to two dichotomous traits measured on each member of the twin pair. For two sample problems, several test procedures that account for the correlation between twins and the correlation between traits are presented. An example based on the Australian population-based twin registry published data is given to illustrate the methodology.


Assuntos
Modelos Estatísticos , Estudos em Gêmeos como Assunto/métodos , Adulto , Asma/epidemiologia , Asma/genética , Asma/imunologia , Austrália/epidemiologia , Simulação por Computador , Feminino , Humanos , Masculino , Método de Monte Carlo , Rinite Alérgica Sazonal/epidemiologia , Rinite Alérgica Sazonal/genética , Rinite Alérgica Sazonal/imunologia , Gêmeos Dizigóticos , Gêmeos Monozigóticos
15.
Stat Med ; 26(18): 3476-86, 2007 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-17149800

RESUMO

Many split-mouth trials are characterized by the pairing of site-specific outcome and baseline data within each segment of a subject's mouth. However when the response variable of interest is binary, methods of statistical analysis for this design are not well developed. In this paper we present several analytic approaches that may be taken to the resulting data, showing how the efficiency of statistical inferences can be improved by appropriately incorporating the baseline information. The advantages and disadvantages of the different approaches are discussed in the context of an example from the published literature. The results from a limited simulation study are also presented.


Assuntos
Ensaios Clínicos como Assunto/métodos , Interpretação Estatística de Dados , Ensaios Clínicos como Assunto/estatística & dados numéricos , Humanos , Ontário
16.
Stat Med ; 26(1): 2-19, 2007 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-17136746

RESUMO

The design and analysis of cluster randomized trials has been a recurrent theme in Statistics in Medicine since the early volumes. In celebration of 25 years of Statistics in Medicine, this paper reviews recent developments, particularly those that featured in the journal. Issues in design such as sample size calculations, matched paired designs, cohort versus cross-sectional designs, and practical design problems are covered. Developments in analysis include modification of robust methods to cope with small numbers of clusters, generalized estimation equations, population averaged and cluster specific models. Finally, issues on presenting data, some other clustering issues and the general problem of evaluating complex interventions are briefly mentioned.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Teorema de Bayes , Biometria/história , Análise por Conglomerados , Estudos de Coortes , Estudos Transversais , Interpretação Estatística de Dados , História do Século XX , História do Século XXI , Humanos , Modelos Estatísticos , Editoração/história , Ensaios Clínicos Controlados Aleatórios como Assunto/história , Tamanho da Amostra
17.
Verh Dtsch Ges Pathol ; 90: 203-9, 2006.
Artigo em Alemão | MEDLINE | ID: mdl-17867598

RESUMO

Tissue banks containing human malignant and benign tissue have become highly important for modem cancer research. They provide an excellent source of information with respect to pathological states and processes. Nowadays tissue samples can be examined using a broad variety of molecular biology methods, at the levels of DNA, RNA and protein. However, these new possibilities impose great expectations from the user side towards tissue banks and their associated databases. Nowadays a database that only manages tissue samples is not timely anymore. In fact a modern database should be capable of registering arbitraty amounts of tissue relevant information in an easily searchable way. In order to simplify the often complicated and time consuming process of data collection, we have developed a software solution that centralizes various aspects of tumor tissue banking. The main task of this software is not only to administer tissue samples but also to provide a centralized data platform for scientists which support their research. To achieve our goals we have constructed a tissue database which is supported by an Oracle System. The access to this database has been made possible with a light-weight, self-developed Java Client Program. The system possesses high levels of security and the access to information in the database is strictly controlled by preset permissions. A flexible search mechanism is also readily available for speedy data extraction according to various criteria. This solution provides us with an "All-in-one" tool for the purpose of flexible and efficient data collection and management in cancer research.


Assuntos
Bases de Dados Factuais/normas , Neoplasias/patologia , Bancos de Tecidos/organização & administração , Humanos , Gestão da Informação/tendências
18.
Endocr J ; 52(2): 281-5, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15863962

RESUMO

The simultaneous occurrence of different types of thyroid carcinoma in a single patient is an unusual event. We report the case of a 52-year-old man with the history of two previous thyroid operations for benign goiters, who developed a recurrent goiter. The patient was referred to our department for thyroidectomy. In the pathohistological examination the specimen showed a 5 cm follicular carcinoma and a 0.3 cm papillary microcarcinoma in the right lobe as well as a 1.5 cm medullary carcinoma in the left lobe. All tumors were clearly separated from each other, representing the pure entity of each type. Postoperatively, RET germline mutation was ruled out by sequence analysis of peripheral blood leucocytes. Postoperative I-131-radioiodine scan showed multiple lung and liver metastases, while calcitonin was negative. There is no known common cause of these three different tumor types and they developed most independently from each other. The personal history of our patient was interesting in two aspects: (1) he suffered a period of severe staphylococcal sepsis with temporal immunosuppression and (2) he worked for long years as a coremaker in a foundry. This work represented possible long term exposure to inhalative carcinogenous toxins like hydrazine, which caused thyroid parafollicular cell adenomas in an animal model.


Assuntos
Adenocarcinoma Folicular/patologia , Carcinoma Medular/patologia , Carcinoma Papilar/patologia , Bócio/complicações , Neoplasias Primárias Múltiplas , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/complicações , Carcinoma Medular/complicações , Carcinoma Papilar/complicações , Bócio/patologia , Bócio/cirurgia , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Recidiva , Neoplasias da Glândula Tireoide/complicações , Tireoidectomia
19.
Eur J Clin Pharmacol ; 61(2): 103-11, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15711832

RESUMO

OBJECTIVE: Triflusal has been shown to exert neuroprotective effects by downregulating molecules considered responsible for the development of Alzheimer's disease (AD). The aim of this study was to develop a population pharmacokinetic model to characterize plasma and cerebrospinal fluid (CSF) pharmacokinetics of the main active metabolite of triflusal-HTB (2-hydroxy-4-trifluoro-methylbenzoic acid)-in healthy volunteers. METHODS: Data from two studies were combined. Study A: subjects received single oral doses of triflusal 900 mg. Triflusal and HTB plasma concentrations were extensively measured. Study B: triflusal 600 mg once daily was administered orally for 14 days. HTB plasma and CSF concentrations were determined in healthy volunteers. Population pharmacokinetic modeling was performed using NONMEM. RESULTS: A one-compartmental model with rapid first-order absorption for triflusal and first-order formation of HTB best described plasma concentrations. Triflusal elimination rate constant was 50 times faster than that estimated for the metabolite. CSF concentrations of HTB ranged between 0.011 microg/ml and 0.341 microg/ml. A CSF-plasma partition coefficient of 0.002 and a k(e0) value of 0.059 h(-1) were estimated by means of population modeling. CONCLUSION: In the present study in healthy volunteers, HTB penetrated into the CSF in a range of concentrations experimentally proven to have protective effects in AD. These concentrations suggest that triflusal could be used in the treatment of central nervous system diseases in doses similar to those used in cardiovascular diseases. Access to the CSF compartment was characterized by a slow equilibrium rate constant and a low CSF-plasma partition coefficient.


Assuntos
Fármacos Neuroprotetores/farmacocinética , Salicilatos/líquido cefalorraquidiano , Salicilatos/farmacocinética , Adulto , Barreira Hematoencefálica/metabolismo , Cromatografia Líquida de Alta Pressão , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Modelos Biológicos , Fármacos Neuroprotetores/sangue , Fármacos Neuroprotetores/líquido cefalorraquidiano , Salicilatos/sangue
20.
Z Gastroenterol ; 42(8): 743-7, 2004 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-15314728

RESUMO

A case of a 32-year-old male patient with lower gastrointestinal bleeding is reported as an initial manifestation of Behçet's disease. The early diagnosis of this chronic-systemic disease is often very difficult, in particular with regard to the differentiation from chronic inflammatory bowel diseases. In addition, lower gastrointestinal bleeding is a rare manifestation of Behçet's disease. An immunosuppressive therapy was initiated and the course of the disease with recurrent oral ulcerations gave evidence for the diagnosis. Further bleeding episodes or other gastrointestinal symptoms have not been observed during a follow-up period of 36 months. The diagnostic problems and the therapeutic management of the disease are discussed in relation to neighbouring entities.


Assuntos
Síndrome de Behçet/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Adulto , Azatioprina/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Doença Crônica , Diagnóstico Diferencial , Hemorragia Gastrointestinal/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Resultado do Tratamento
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