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1.
J Chem Phys ; 156(15): 154111, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35459323

RESUMO

The link between the static dielectric constant and the microscopic intermolecular interactions is the Kirkwood g1 factor, which depends on the orientational structure of the fluid. Over the years, there have been several attempts to provide an accurate description of the orientational structure of dipolar fluids using molecular theories. However, these approaches were either limited to mean-field approximations for the pair correlation function or, more recently, limited to adjusting the orientational dependence to simulation data. Here, we derive a theory for the dielectric constant of dipolar hard-sphere fluids using the augmented modified mean-field approximation. Qualitative agreement is achieved throughout all relevant thermodynamic states, as demonstrated by a comparison with simulation data from the literature. Excellent quantitative agreement can be obtained using a single empirical scaling factor, the physical origin of which is analyzed and accounted for. In order to predict the dielectric constant of the Stockmayer fluid (Lennard-Jones plus dipole potential), we use an adjusted version of the expression for the dipolar hard-sphere fluid. Comparing theoretical predictions with newly generated simulation data, we show that it is possible to obtain excellent agreement with simulation by performing the calculations at a corresponding state using the same scaling factor. Finally, we compare the theoretical orientational structure of the Stockmayer fluid with that obtained from simulations. The simulated structure is calculated following a post-processing methodology that we introduce by deriving an original expression that relates the proposed theory to the histogram of relative dipole angles.

2.
Phys Rev Lett ; 125(11): 117208, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32975965

RESUMO

We investigate spin dynamics of microstates in artificial spin ice (ASI) in Ni_{81}Fe_{19} nanomagnets arranged in an interconnected kagome lattice using microfocus Brillouin light scattering, broadband ferromagnetic resonance, magnetic force microscopy, x-ray photoemission electron microscopy, and simulations. We experimentally reconfigure microstates in ASI using a 2D vector field protocol and apply microwave-assisted switching to intentionally trigger reversal. Our work is key for the creation of avalanches inside the kagome ASI and reprogrammable magnonics based on ASIs.

3.
Br J Surg ; 106(13): 1837-1846, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31424576

RESUMO

BACKGROUND: Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. METHODS: Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. RESULTS: Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). CONCLUSION: Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM.


ANTECEDENTES: La resección secundaria de metástasis hepáticas de cáncer colorrectal (colorectal cancer liver metastases, CRLM) inicialmente irresecables puede prolongar la supervivencia. Se desconoce el valor añadido de la radioterapia interna selectiva (selective internal radiation therapy, SIRT). Este estudio evaluó el cambio en la resecabilidad técnica de las CRLM secundario a la adición de SIRT a una quimioterapia tipo FOLFOX. MÉTODOS: Las pruebas de radioimagen basales y durante el seguimiento de pacientes tratados con un régimen FOLFOX modificado (mFOLFOX6: fluorouracilo, leucovorina, oxaliplatino) ± bevacizumab (grupo control) versus mFOLFOX6 (± bevacizumab) más SIRT usando microesferas de resina de yttrium-90, en el ensayo de fase III SIRFLOX, fueron revisadas por 3-5 (de 14) cirujanos expertos hepatobiliares para determinar la resecabilidad. Los expertos efectuaron la revisión de forma ciega unos respecto a otros en relación con la asignación al tratamiento, estado de la enfermedad extra-hepática y situación clínica en el momento del estudio radiológico. La resecabilidad técnica se definió como ≥ 60% de revisores evaluando las metástasis del paciente como quirúrgicamente resecables. RESULTADOS: Fueron evaluables un total de 472 pacientes (control, n = 228; SIRT, n = 244). No hubo diferencias significativas basales en la proporción de metástasis hepáticas técnicamente resecables entre SIRT (29/244; 11,9%) y el grupo control (25/228; 11,0%: P = 0,775). Durante el seguimiento y en ambos brazos de tratamiento, un número significativamente mayor de pacientes se consideraron técnicamente resecables en comparación con la situación basal (54/472 (11,4%) basal y 159/472 (33,7%) al seguimiento). Hubo más pacientes resecables en el grupo SIRT que en el control (93/244 (38,1%) y 66/228 (28,9%); P < 0,001, respectivamente). CONCLUSIÓN: La adición de SIRT a la quimioterapia puede mejorar la resecabilidad de las CRLM irresecables.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/terapia , Neoplasias Colorretais/terapia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
4.
Phys Rev Lett ; 117(15): 157202, 2016 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-27768325

RESUMO

We report the observation of the anisotropic polar magneto-optical Kerr effect in thin layers of epitaxial Fe/GaAs(001) at room temperature. A clear twofold symmetry of the Kerr rotation angle depending on the orientation of the linear polarization of the probing laser beam with respect to the crystallographic directions of the sample is detected for ultrathin magnetic films saturated out of the film plane. The amplitude of the anisotropy decreases with increasing Fe film thickness, suggesting that the interfacial region is the origin of the anisotropy. The twofold symmetry is fully reproduced by model calculations based on an interference of interfacial Bychkov-Rashba and Dresselhaus spin-orbit coupling.

5.
Mol Psychiatry ; 20(12): 1489-98, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25560758

RESUMO

Recent genetic data on schizophrenia (SCZ) have suggested that proteins of the postsynaptic density of excitatory synapses have a role in its etiology. Mutations in the three SHANK genes encoding for postsynaptic scaffolding proteins have been shown to represent risk factors for autism spectrum disorders and other neurodevelopmental disorders. To address if SHANK2 variants are associated with SCZ, we sequenced SHANK2 in 481 patients and 659 unaffected individuals. We identified a significant increase in the number of rare (minor allele frequency<1%) SHANK2 missense variants in SCZ individuals (6.9%) compared with controls (3.9%, P=0.039). Four out of fifteen non-synonymous variants identified in the SCZ cohort (S610Y, R958S, P1119T and A1731S) were selected for functional analysis. Overexpression and knockdown-rescue experiments were carried out in cultured primary hippocampal neurons with a major focus on the analysis of morphological changes. Furthermore, the effect on actin polymerization in fibroblast cell lines was investigated. All four variants revealed functional impairment to various degrees, as a consequence of alterations in spine volume and clustering at synapses and an overall loss of presynaptic contacts. The A1731S variant was identified in four unrelated SCZ patients (0.83%) but not in any of the sequenced controls and public databases (P=4.6 × 10(-5)). Patients with the A1731S variant share an early prodromal phase with an insidious onset of psychiatric symptoms. A1731S overexpression strongly decreased the SHANK2-Bassoon-positive synapse number and diminished the F/G-actin ratio. Our results strongly suggest a causative role of rare SHANK2 variants in SCZ and underline the contribution of SHANK2 gene mutations in a variety of neuropsychiatric disorders.


Assuntos
Proteínas do Tecido Nervoso/genética , Esquizofrenia/genética , Adulto , Animais , Células COS , Chlorocebus aethiops , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Masculino , Mutação , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Estrutura Terciária de Proteína , Ratos , Ratos Sprague-Dawley , Esquizofrenia/metabolismo
6.
Eur J Radiol Open ; 8: 100356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34041308

RESUMO

[This corrects the article DOI: 10.1016/j.ejro.2020.100280.].

7.
Hautarzt ; 61(6): 514-7, 2010 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-20309512

RESUMO

A 31-year-old woman presented with progressive deep linear induration on her lower abdomen, forearms and thighs. These symptoms developed three years after allogenic stem cell transplantation. Furthermore, the patient showed multiple hypopigmented lichenoid papules on the extensor surfaces of the forearms consistent with lichen sclerosus. Histological analysis of a biopsy specimen from her left thigh showed dermal sclerosis extending into the fascia, thus establishing the diagnosis of a rare combination of superficial and deep sclerodermoid chronic graft-versus-host disease. After 7 cycles of extracorporeal photopheresis, a marked resolution of the indurations and a reduction of the modified Rodnan skin score from 12 to 7 were noted.


Assuntos
Anemia Refratária com Excesso de Blastos/terapia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Líquen Escleroso e Atrófico/tratamento farmacológico , Fotoferese , Esclerodermia Difusa/tratamento farmacológico , Transplante de Células-Tronco , Adulto , Atrofia , Biópsia , Doença Crônica , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/patologia , Humanos , Líquen Escleroso e Atrófico/patologia , Esclerodermia Difusa/patologia , Pele/patologia
8.
Water Sci Technol ; 61(4): 1003-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20182080

RESUMO

Large waste water treatment plants (WWTP) often operate nitrification in two different process environments: the cold-dilute sewage is treated in the mainstream nitrification/denitrification system, while the high strength ammonia liquors from sludge dewatering are treated in a separate high temperature reactor (SBR). This study investigates transfer from nitrifier biomass into a two-stage WWTP, commonly referred to as bioaugmentation. Besides the quantitation of ammonia oxidising bacteria (AOB), community differences were analysed with two techniques, denaturing gradient gel electrophoresis and real-time PCR melt curve analysis. It was shown that, without bioaugmentation, two distinct AOB communities establish in the mainstream and in the SBR, respectively. A gradual shift of the two AOB communities with increasing pump rates between the systems could be demonstrated. These molecular findings support process engineering experience, that cycling of waste activated sludge improves the ability of AOB to adapt to different process environments.


Assuntos
Amônia/química , Esgotos , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Biomassa , Reatores Biológicos , Análise por Conglomerados , Eletroforese , Desenho de Equipamento , Nitrogênio/química , Oxigênio/química , Filogenia , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Microbiologia da Água
9.
Eur J Radiol Open ; 7: 100280, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33102639

RESUMO

PURPOSE: To investigate contrast dynamics and artifacts associated with different breathing maneuvers during pulmonary computed tomography angiography (pCTA) in a prospective randomized clinical trial. METHOD: Three different breathing maneuvers (inspiration, expiration, Mueller) were randomly assigned to 146 patients receiving pCTA for suspected pulmonary embolism (PE). Contrast enhancement of central and peripheral arteries and imaging quality of lung parenchyma were compared and analyzed. Results were compared by using the analysis of variances (ANOVA) and Kruskal-Wallis-Test. RESULTS: Mean enhancement in the pulmonary trunk was highest during breath-hold in inspiration (293 HU, range 195-460 HU) compared to Mueller (259 HU, range 136-429 HU, p = 0022) and expiration (267 HU, range 115-376 HU). This was similar for the right pulmonary artery (inspiration 289 HU, range 173-454 HU; Mueller 250 HU, range 119-378 HU; p = 0.007; expiration 257 HU, range 114-366 HU; p = 0.032) and left pulmonary artery (inspiration 280.3 HU, range 170-462 HU; Mueller 245 HU, range 111-371 HU; p = 0.016; expiration 252 HU, range 110-371 HU).Delineation of peripheral arteries was significantly better in inspiration vs Mueller (p = 0.006) and expiration (p = 0.049). Assessment of the lung parenchyma was significantly better in inspiration vs Mueller (p = 0.013) or expiration (p < 0.001). CONCLUSIONS: Resting inspiratory position achieved the highest enhancement levels in central and peripheral pulmonary arteries and best image quality of the pulmonary parenchyma in comparison to other breathing maneuvers. It is necessary to train the maneuver prior to the examination in order to avoid deep inspiration with the risk of suboptimal opacification of the pulmonary arteries.

10.
Science ; 262(5133): 545-7, 1993 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-17733235

RESUMO

Thin films of monatomic fluid constrained between two plane-parallel structured solid walls have been modeled by Monte Carlo simulation under conditions (fixed temperature, chemical potential, and normal stress or load) prevailing in high-precision measurements of surface forces. Several states of the film, corresponding to different numbers of layers of fluid parallel with the walls, are generally consistent with these conditions, but only one is thermodynamically stable; the others are metastable. When the walls are properly aligned, epitaxial solid phases are stable. These melt under shear, eventually becoming metastable, whereupon a drainage (or imbibition) transition occurs, leading to a stable phase with fewer (or more) layers.

11.
Science ; 245(4923): 1223-5, 1989 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-17747884

RESUMO

Monte Carlo and molecular dynamics methods have been used to study the shearing behavior of an atomic fluid between two plane-parallel solid surfaces having the face-centered cubic (100) structure. A distorted, face-centered cubic solid can form epitaxially between surfaces that are separated by distances of one to five atomic diameters. Under these conditions a critical stress must be overcome to initiate sliding of the surfaces over one another at fixed separation, temperature, and chemical potential. As sliding begins, a layer of solid exits the space between the surfaces and the remaining layers become fluid.

12.
Water Sci Technol ; 58(8): 1547-53, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19001706

RESUMO

This paper presents benefits and potential drawbacks of thermal pre-hydrolysis of sewage sludge from an operator's prospective. The innovative continuous Thermo-Pressure-Hydrolysis Process (TDH) has been tested in full-scale at Zirl wastewater treatment plant (WWTP), Austria, and its influence on sludge digestion and dewatering has been evaluated. A mathematical plant-wide model with application of the IWA Activated Sludge Model No.1 (ASM1) and the Anaerobic Digestion Model No.1 (ADM1) has been used for a systematic comparison of both scenarios--operational plant performance with and without thermal pre-hydrolysis. The impacts of TDH pre-hydrolysis on biogas potential, dewatering performance and return load in terms of ammonia and inert organic compounds (Si) have been simulated by the calibrated model and are displayed by Sankey mass flow figures. Implementation of full scale TDH process provided higher anaerobic degradation efficiency with subsequent increased biogas production (+75-80%) from waste activated sludge (WAS). Both effects--enhanced degradation of organic matter and improved cake's solids content from 25.2 to 32.7% TSS--promise a reduction in sludge disposal costs of about 25%. However, increased ammonia release and generation of soluble inerts Si was observed when TDH process was introduced.


Assuntos
Resíduos Industriais , Poluentes da Água/isolamento & purificação , Hidrólise , Modelos Teóricos , Esgotos
13.
Water Sci Technol ; 58(7): 1467-73, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18957761

RESUMO

Thermal hydrolysis is known for an efficient sludge disintegration capability to enhance biogas potential--but to which extent? Obviously, residual VSS concentration in digested sludge gives not sufficient information to predict additional biogas potential. In this paper, different types of waste activated sludge (WAS) were pre-hydrolysed by a full-scale Thermo-Pressure-Hydrolysis Process (Thermo-Druck-Hydrolyse, TDH) and break-down mechanisms on specific organic compounds were investigated. The IWA Anaerobic Digestion Model No.1 (ADM1) has been used for a systematic analysis of monitoring data gained from experimental work. The TDH process combined with anaerobic digestion can be well described by a modified ADM1 model that includes an X(P)-fraction (inactivated aerobic biomass and their decay products). More rapid and more complete degradation of TDH-treated sludge is represented by calibrated disintegration rate and disintegration factors, while biokinetic parameters of acetogenesis and methanogenesis show no sensitivity. TDH process impacts mainly biomass and decay products while inerts Xi already contained in the raw wastewater are hardly converted. Final concentration of soluble inerts in digestion effluent has been increased from 2% to 9% of influent COD due to thermal hydrolysis. An increase in biogas generation (ca. +80%) and in ammonia release (ca. +75%) can be explained by complete degradation of cell mass.


Assuntos
Esgotos/química , Eliminação de Resíduos Líquidos/instrumentação , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Biodegradação Ambiental , Hidrólise , Modelos Teóricos , Compostos Orgânicos/química , Compostos Orgânicos/metabolismo , Pressão , Esgotos/microbiologia , Temperatura
14.
Proc Inst Mech Eng H ; 221(6): 677-86, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17937206

RESUMO

This paper presents a lumped-parameter model for the big-toe region that investigates the effect of plantar pressure on the diameter of the blood vessels, specifically the arteries, in the presence of arterial and/or tissue changes. The model developed in this paper uses a multi-domain energy system approach to develop the lumped-parameter differential equations. Blood flow is modelled as fluidic flow through compliant pipes that have inertia, stiffness, and damping. The tissue material is treated as a soft compliant material that transmits the external force to the blood vessels. Conclusions have been drawn to show the effect of plantar pressure, tissue damage, and their combination on the diameter of the blood vessels. The principles used here can be used to model the entire foot and the model used to investigate the effect of plantar pressure, tissue damage, and arterial changes on different parts of the foot. The work presented here may also have applications in other vascular diseases.


Assuntos
Artérias/fisiopatologia , Velocidade do Fluxo Sanguíneo , Pé Diabético/fisiopatologia , Pé/irrigação sanguínea , Pé/fisiopatologia , Modelos Biológicos , Pressão Sanguínea , Simulação por Computador , Elasticidade , Humanos , Pressão , Estresse Mecânico
15.
Proc Inst Mech Eng H ; 221(2): 173-83, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17385571

RESUMO

Although among designs of prosthetics there have been some successes in the design of functional robotic implants, there remain many issues and challenges concerned with the failure to meet the 'ideal' requirements of a satisfactory prosthetic. These 'ideals' require the device to be easy to control, comfortable to wear, and cosmetically pleasing. Because the literature on prosthetics and robotic implants are voluminous, this review focuses on four topics to determine key challenges and opportunities underlying these interdisciplinary research areas: firstly, an artificial hand as a biomimetic; secondly, prosthetic implants (electromyography signals and control); thirdly, prosthetic implants and tissue reactions to the material(s) of implants; fourthly, how inflammatory responses of cells and tissues surrounding implanted sensors interfere with the signal transmission of such sensors. This review also notes the importance of the biological interfaces that robotic implants and other prosthetic devices are in contact with and how an improved knowledge of pathophysiological changes at such biological interfaces will lead to improved and more biocompatible designs of prosthetics. This review concludes with the vision that, to develop a design that satisfies the above 'ideals', an interdisciplinary team of biomedical and tissue engineers, and biomaterial and biomedical scientists is needed to work together holistically and synergistically.


Assuntos
Materiais Biomiméticos , Ergonomia , Sistemas Homem-Máquina , Próteses e Implantes , Robótica/instrumentação , Interface Usuário-Computador , Análise de Falha de Equipamento , Desenho de Prótese , Robótica/métodos
16.
Water Sci Technol ; 56(11): 1-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18057635

RESUMO

In the framework of a program for environmental protection conducted by the German mountaineers' club (DAV) problems emerging from residual solids accumulating in on-site wastewater treatment plants of mountain refuges were investigated. To handle these problems in an ecologically and economically reasonable way two devices for solar-supported treatment of sludge and bio-solids have been developed. These units support gravity-filtration and evaporation of liquid sludge as well as thermal acceleration of composting processes. Two solar sludge dryers were installed and operated without external energy supply at alpine refuges treating primary and secondary sludge, respectively. Batch-filling during the season could increase load capacity and a total solids concentration of up to 40% could be achieved before discharge at the beginning of the next season. The promising results from the solar sludge dryer encouraged for the development of a solar composter. The period of temperature levels suitable for composting biosolids in mountain areas can be extended considerably by application of this technology--measured temperature distribution indicated no freezing at all.


Assuntos
Esgotos , Luz Solar , Eliminação de Resíduos Líquidos/métodos , Altitude , Áustria , Umidade , Solo , Temperatura
17.
Water Sci Technol ; 55(10): 21-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17564366

RESUMO

Different digestion technologies for various substrates are addressed by the generic process description of Anaerobic Digestion Model No. 1. In the case of manure or agricultural wastes a priori knowledge about the substrate in terms of ADM1 compounds is lacking and influent characterisation becomes a major issue. The actual project has been initiated for promotion of biogas technology in agriculture and for expansion of profitability also to rather small capacity systems. In order to avoid costly individual planning and installation of each facility a standardised design approach needs to be elaborated. This intention pleads for bio kinetic modelling as a systematic tool for process design and optimisation. Cofermentation under field conditions was observed, quality data and flow data were recorded and mass flow balances were calculated. In the laboratory different substrates have been digested separately in parallel under specified conditions. A configuration of four ADM1 model reactors was set up. Model calibration identified disintegration rate, decay rates for sugar degraders and half saturation constant for sugar as the three most sensitive parameters showing values (except the latter) about one order of magnitude higher than default parameters. Finally, the model is applied to the comparison of different reactor configurations and volume partitions. Another optimisation objective is robustness and load flexibility, i.e. the same configuration should be adaptive to different load situations only by a simple recycle control in order to establish a standardised design.


Assuntos
Anaerobiose , Bactérias/metabolismo , Reatores Biológicos , Esterco/microbiologia , Metano/biossíntese , Modelos Teóricos , Eliminação de Resíduos Líquidos/métodos
18.
J Dev Orig Health Dis ; 6(5): 390-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26268724

RESUMO

David Barker established growth as a seminal link between early development and later health attainment and disease risk. This was nothing less than a paradigm shift in health and medicine, turning the focus of disease causality away from contemporary environmental influences to earliest growth as a time when functional anatomy and physiology sets in place critical structures and function for a lifetime. Barker's prodigious work investigated time- and place-specific interactions between maternal condition and exogenous environmental influences, focusing on how growth unfolds across development to function as a mechanistic link to ensuing health. Subsequent applications do not always attend to the specificity and sensitivity issues included in his original work, and commonly overlook the long-standing methods and knowledge base of auxology. Methodological areas in need of refinement include enhanced precision in how growth is represented and assessed. For example, multiple variables have been used as a referent for 'growth,' which is problematic because different body dimensions grow by different biological clocks with unique functional physiologies. In addition, categorical clinical variables obscure the spectrum of variability in growth experienced at the individual level. Finally, size alone is a limited measure as it does not capture how individuals change across age, or actually grow. The ground-breaking notion that prenatal influences are important for future health gave rise to robust interest in studying the fetus. Identifying the many pathways by which size is realized permits targeted interventions addressing meaningful mechanistic links between growth and disease risk to promote health across the lifespan.


Assuntos
Desenvolvimento Fetal , Fenômenos Fisiológicos da Nutrição , Obesidade/embriologia , Feminino , Humanos , Lactente , Masculino
19.
Clin Pharmacokinet ; 20(2): 151-66, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2029806

RESUMO

The optimisation of antiarrhythmic drug therapy is dependent on the definitions and methods of short term efficacy testing and the characteristics of those drugs used for rhythm disturbances. The choice of an initial antiarrhythmic drug dosage is highly empirical, and will remain so until the measurement of free concentrations, enantiomeric fractions and genetic phenotyping becomes routine. However, the clinician can devise an efficient initial dosage for efficacy testing procedures based on pharmacokinetic principles and disposition variables in the literature. In this regard, a nomogram for commonly used agents and dosages was constructed and is offered as a guide to accomplish this goal. Verification of the accuracy and usefulness of this nomogram in a prospective manner in patients with symptomatic tachyarrhythmias is still required. On a long term basis, dosage regimens can be modified by the use of pharmacokinetic principles and patient-specific target concentrations, in accordance with the methods used to monitor arrhythmia recurrence and drug-related side effects.


Assuntos
Antiarrítmicos/administração & dosagem , Antiarrítmicos/farmacocinética , Arritmias Cardíacas/tratamento farmacológico , Humanos
20.
Am J Cardiol ; 67(4): 300-4, 1991 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-1990794

RESUMO

To evaluate the effects of calcium pretreatment on the disposition and electrocardiographic effects of verapamil, 8 healthy male volunteers received treatment in each of 3 phases in a randomized, double-blind, crossover manner. Phase I denoted 10 ml of 0.9% intravenous sodium chloride followed by 10 mg of intravenous verapamil; phase II denoted 10 ml of 10% intravenous calcium chloride followed by 4 ml of 0.9% intravenous sodium chloride; and phase III denoted 10 ml of 10% intravenous calcium chloride followed by 10 mg of intravenous verapamil. Blood samples for the determination of verapamil concentrations were drawn at 5, 10, 15, 20, 30, 45, 60 and 90 minutes, and at 2, 4, 6, 10 and 24 hours. Blood pressure, heart rate and PR intervals were also measured at these times. Pretreatment of verapamil with intravenous calcium did not alter the disposition of intravenous verapamil. Blood pressure was not significantly altered in any treatment phase, although calcium tended to increase mean arterial pressure and verapamil abolished this effect. Calcium had no significant affect on verapamil-induced PR prolongation (maximum percent change in PR interval: phase I = 19 +/- 11%, phase III = 18 +/- 7%; time to maximal prolongation: phase I = 0.38 +/- 0.21 hours, phase III = 0.37 +/- 0.26 hours; and area under the percent change in PR vs time curve: phase I = 15.5 +/- 10, phase III = 21 +/- 9). Verapamil caused a reflex increase in heart rate of similar magnitude in both phases I and III (24 +/- 10% and 21 +/- 7%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Cloreto de Cálcio/uso terapêutico , Eletrocardiografia/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipotensão/prevenção & controle , Verapamil/farmacologia , Adolescente , Adulto , Análise de Variância , Cloreto de Cálcio/administração & dosagem , Método Duplo-Cego , Humanos , Hipotensão/induzido quimicamente , Infusões Intravenosas , Masculino , Distribuição Aleatória , Valores de Referência , Verapamil/administração & dosagem , Verapamil/sangue , Verapamil/farmacocinética
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