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1.
Phys Chem Chem Phys ; 22(10): 5785-5796, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32105280

RESUMO

The laboratory study of prebiotic molecules interacting with solar wind ions is important to understand their role in the emergence of life in the complex context of the astrochemistry of circumstellar environments. In this work, we present the first study of the interaction of hydantoin (C3N2O2H4, 100 a.m.u.) with solar wind minority multi-charged ions: O6+ at 30 keV and He2+ at 8 keV. The fragmentation mass spectra as well as correlation maps resulting from the interaction are presented and discussed in this paper. Prompt and delayed dissociations from metastable states of the ionized molecule have been observed and the corresponding lifetimes measured. Experimental results are completed by quantum Density Functional Theory (DFT) calculations for energies, structures and dynamics (Internal Reaction Coordinates and Dynamic Reaction Coordinates) of the molecule for its different reachable charge states and the major observed fragmentation pathways. These calculations show that the molecule can only support two charges before spontaneously dissociating in agreement with the experimental observations. Calculations also demonstrate that hydantoin's ring opens after double ionization of the molecule which may enhance its reactivity in the background of biological molecule formation in a cirmcumstellar environment. For the major experimentally observed fragmentations (like 44 a.m.u./56 a.m.u. dissociation), Internal Reaction Coordinate (IRC) calculations were performed pointing out for example the important role of hydrogen transfer in the fragmentation processes.

2.
PLoS One ; 15(1): e0227629, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31999696

RESUMO

Web-based experimentation with uncompensated and unsupervised samples allows for a larger and more diverse sample population, more generalizable results, and faster theory to experiment cycle. Given that participants are unsupervised, it is still unknown whether the data collected in such settings would be of sufficiently high quality to support robust conclusions. Therefore, we investigated the feasibility of conducting such experiments online using virtual environment technologies. We conducted a conceptual replication of two prior experiments that have been conducted in virtual environments. Our results replicate findings previously obtained in conventional laboratory settings. These results hold across different device types of participants (ranging from desktop, through mobile devices to immersive virtual reality headsets), suggesting that experiments can be conducted online with uncompensated samples in virtual environments.


Assuntos
Negociação/psicologia , Navegação Espacial , Realidade Virtual , Adolescente , Adulto , Idoso , Telefone Celular , Criança , Computadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Experimentação Humana não Terapêutica , Sistemas On-Line , Adulto Jovem
3.
Rev Sci Instrum ; 89(4): 043104, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29716322

RESUMO

In the present paper, we describe a new home-built crossed-beam apparatus devoted to ion-induced ionization and fragmentation of isolated biologically relevant molecular systems. The biomolecular ions are produced by an electrospray ionization source, mass-over-charge selected, accumulated in a 3D ion trap, and then guided to the extraction region of an orthogonal time-of-flight mass spectrometer. Here, the target molecular ions interact with a keV atomic ion beam produced by an electron cyclotron resonance ion source. Cationic products from the collision are detected on a position sensitive detector and analyzed by time-of-flight mass spectrometry. A detailed description of the operation of the setup is given, and early results from irradiation of a protonated pentapeptide (leucine-enkephalin) by a 7 keV He+ ion beam are presented as a proof-of-principle.


Assuntos
Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas em Tandem/instrumentação , Elétrons , Encefalina Leucina/química , Desenho de Equipamento , Gases/química , Hélio/química , Íons/química , Cinética , Estudo de Prova de Conceito
4.
Phys Chem Chem Phys ; 20(22): 15052-15060, 2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29790511

RESUMO

Ionization, fragmentation and molecular growth have been studied in collisions of 22.5 keV He2+- or 3 keV Ar+-projectiles with pure loosely bound clusters of coronene (C24H12) molecules or with loosely bound mixed C60-C24H12 clusters by using mass spectrometry. The heavier and slower Ar+ projectiles induce prompt knockout-fragmentation - C- and/or H-losses - from individual molecules and highly efficient secondary molecular growth reactions before the clusters disintegrate on picosecond timescales. The lighter and faster He2+ projectiles have a higher charge and the main reactions are then ionization by ions that are not penetrating the clusters. This leads mostly to cluster fragmentation without molecular growth. However, here penetrating collisions may also lead to molecular growth but to a much smaller extent than with 3 keV Ar+. Here we present fragmentation and molecular growth mass distributions with 1 mass unit resolution, which reveals that the same numbers of C- and H-atoms often participate in the formation and breaking of covalent bonds inside the clusters. We find that masses close to those with integer numbers of intact coronene molecules, or with integer numbers of both intact coronene and C60 molecules, are formed where often one or several H-atoms are missing or have been added on. We also find that super-hydrogenated coronene is formed inside the clusters.

5.
Phys Chem Chem Phys ; 19(30): 19665-19672, 2017 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-28503696

RESUMO

We report on studies of collisions between 3 keV Ar+ projectile ions and neutral targets of isolated 1,3-butadiene (C4H6) molecules and cold, loosely bound clusters of these molecules. We identify molecular growth processes within the molecular clusters that appears to be driven by knockout processes and that could result in the formation of (aromatic) ring structures. These types of reactions are not unique to specific projectile ions and target molecules, but will occur whenever atoms or ions with suitable masses and kinetic energies collide with aggregates of matter, such as carbonaceous grains in the interstellar medium or aerosol nanoparticles in the atmosphere.

6.
Phys Chem Chem Phys ; 19(30): 19609-19618, 2017 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-28393947

RESUMO

We present a combined experimental and theoretical study of the fragmentation of multiply-charged γ-aminobutyric acid molecules (GABAz+, z = 2, 3) in the gas phase. The combination of ab initio molecular dynamics simulations with multiple-coincidence mass spectrometry techniques allows us to observe and identify doubly-charged fragments in coincidence with another charged moiety. The present results indicate that double and triple electron capture lead to the formation of doubly-charged reactive nitrogen and oxygen species (RNS and ROS) with different probabilities due to the different charge localisation and fragmentation behaviour of GABA2+ and GABA3+. The MD simulations unravel the fast (femtosecond) formation of large doubly charged species, observed on the experimental microsecond timescale. The excess of positive charge is stabilised by the presence of cyclic X-member (X = 3-5) ring structures. 5-Member cyclic molecules can sequentially evaporate neutral moieties, such as H2, H2O and CO2, leading to smaller doubly charged fragments as those observed in the experiments.


Assuntos
Argônio/química , Ácido gama-Aminobutírico/química , Elétrons , Gases/química , Íons/química , Simulação de Dinâmica Molecular , Teoria Quântica , Espécies Reativas de Nitrogênio/química , Espécies Reativas de Oxigênio/química , Espectrometria de Massas por Ionização por Electrospray
7.
Epilepsy Behav ; 66: 74-79, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28038390

RESUMO

PURPOSE: The objective of this work was to review systematically the efficacy and tolerability of perampanel (PER) in residential patients of an epilepsy center. METHOD: We adopted an industry-independent noninterventional retrospective evaluation on the basis of the paper and electronic records complemented by personal information on the part of the treating neurologists. All patients (N=26, 15 females, mean age: 30, range 21-55years) started on PER from its introduction to the market in September 2012 until December 15th 2013 were included. Evaluation was carried out after 6, 12, and 24months of PER treatment. Changes in seizure frequency were calculated as the number of seizures during three months on PER compared to a three-month baseline period. The Clinical Global Impression Scale served as an instrument to record changes in seizure intensity beyond numerical values. Adverse effects were documented by means of the Liverpool Adverse Events Profile. RESULTS: Most patients had structural or metabolic epilepsy, 2 patients suffered from Lennox-Gastaut syndrome, 2 from other symptomatic generalized epilepsy. All patients had grade III drug-resistant epilepsy. All patients had additional cognitive deficits of different degree. The retention rates were 61.5% after 6months, 46.2% after 12months, and 42.3% after 24months. The responder rates were 11.5% after 6months, 23.1% after 12months, and 7.7% after 24months. Partial responders (positive CGI and/or seizure reduction <50%) included, the respective values were 26.9%, 38.5%, and 23.1%. Only 1 patient was seizure free at 12months (but not at 24months). A loss of efficacy in the second year of treatment was suspected but the decrease of the responder rate could also be ascribed to a number of different circumstances. Adverse effects in the psychiatric field like irritability, aggression, increased sensitivity, and suicidal ideation/behavior occurred in 50% of the patients. They were the main reason to discontinue PER. CONCLUSIONS: After one year of treatment PER showed reasonable efficacy in a particularly difficult-to-treat population. Psychiatric adverse effects forced discontinuation in many cases.


Assuntos
Anticonvulsivantes/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/psicologia , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/psicologia , Piridonas/uso terapêutico , Adulto , Agressão/efeitos dos fármacos , Anticonvulsivantes/efeitos adversos , Disfunção Cognitiva/diagnóstico , Epilepsia Resistente a Medicamentos/diagnóstico , Feminino , Humanos , Humor Irritável/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Estudos Retrospectivos , Ideação Suicida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Phys Chem Chem Phys ; 18(25): 16721-9, 2016 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-27271080

RESUMO

The fragmentation of uracil molecules and pure and nano-hydrated uracil clusters by (12)C(4+) ion impact is investigated. This work focuses on the fragmentation behavior of complex systems and the effect of the environment. On the one hand, it is found that the environment in the form of surrounding uracil or water molecules has a significant influence on the fragmentation dynamics, providing an overall 'protective' effect, while on the other hand we observe the opening of specific fragmentation channels. In particular, we report on the first observation of a series of hydrated fragments. This indicates a strong interaction between uracil and water molecules, holding the water clusters bound to the observed molecular fragments.

9.
J Phys Chem Lett ; 6(9): 1536-42, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-26263308

RESUMO

The present work combines experimental and theoretical studies of the collision between keV ion projectiles and clusters of pyrene, one of the simplest polycyclic aromatic hydrocarbons (PAHs). Intracluster growth processes induced by ion collisions lead to the formation of a wide range of new molecules with masses larger than that of the pyrene molecule. The efficiency of these processes is found to strongly depend on the mass and velocity of the incoming projectile. Classical molecular dynamics simulations of the entire collision process-from the ion impact (nuclear scattering) to the formation of new molecular species-reproduce the essential features of the measured molecular growth process and also yield estimates of the related absolute cross sections. More elaborate density functional tight binding calculations yield the same growth products as the classical simulations. The present results could be relevant to understand the physical chemistry of the PAH-rich upper atmosphere of Saturn's moon Titan.

10.
J Phys Chem A ; 119(37): 9581-9, 2015 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-26243533

RESUMO

We present a combined experimental and theoretical study of the ionization of N-acetylglycine molecules by 48 keV O(6+) ions. We focus on the single ionization channel of this interaction. In addition to the prompt fragmentation of the N-acetylglycine cation, we also observe the formation of metastable parent ions with lifetimes in the microsecond range. On the basis of density functional theory calculations, we assign these metastable ions to the diol tautomer of N-acetylglycine. In comparison with the simple amino acids, the tautomerization rate is higher because of the presence of the peptide bond. The study of a simple biologically relevant molecule containing a peptide bond allows us to demonstrate how increasing the complexity of the structure influences the behavior of the ionized molecule.


Assuntos
Glicina/análogos & derivados , Fragmentos de Peptídeos/química , Teoria Quântica , Cátions , Glicina/química , Modelos Químicos , Estrutura Molecular
11.
Chemphyschem ; 16(11): 2389-96, 2015 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-26102370

RESUMO

Collisions between O(3+) ions and neutral clusters of amino acids (alanine, valine and glycine) as well as lactic acid are performed in the gas phase, in order to investigate the effect of ionizing radiation on these biologically relevant molecular systems. All monomers and dimers are found to be predominantly protonated, and ab initio quantum-chemical calculations on model systems indicate that for amino acids, this is due to proton transfer within the clusters after ionization. For lactic acid, which has a lower proton affinity than amino acids, a significant non-negligible amount of the radical cation monomer is observed. New fragment-ion channels observed from clusters, as opposed to isolated molecules, are assigned to the statistical dissociation of protonated molecules formed upon ionization of the clusters. These new dissociation channels exhibit strong delayed fragmentation on the microsecond time scale, especially after multiple ionization.


Assuntos
Aminoácidos/química , Ácido Láctico/química , Gases/química , Íons/química , Prótons , Teoria Quântica , Espectrometria de Massas por Ionização por Electrospray , Termodinâmica
12.
Phys Chem Chem Phys ; 17(26): 16767-78, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26035826

RESUMO

We present a combined experimental and theoretical study of the fragmentation of doubly positively charged ß-alanine molecules in the gas phase. The dissociation of the produced dicationic molecules, induced by low-energy ion collisions, is analysed by coincidence mass spectrometric techniques; the coupling with ab initio molecular dynamics simulations allows rationalisation of the experimental observations. The present strategy gives deeper insights into the chemical mechanisms of multiply charged amino acids in the gas phase. In the case of the ß-alanine dication, in addition to the expected Coulomb explosion and hydrogen migration processes, we have found evidence of hydroxyl-group migration, which leads to unusual fragmentation products, such as hydroxymethyl cation, and is necessary to explain some of the observed dominant channels.


Assuntos
Gases/química , Hidróxidos/química , beta-Alanina/química , Cátions/química , Simulação de Dinâmica Molecular
13.
Epilepsy Behav ; 44: 234-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25836054

RESUMO

PURPOSE: The purpose of this study was to evaluate retrospectively the efficacy and tolerability of retigabine (RTG) in residential patients of an epilepsy center. METHOD: We used an industry-independent noninterventional retrospective evaluation on the basis of paper and electronic records plus interrogation of the treating neurologists. All patients (N=20; 7 females; mean age: 31.8, range: 18-54years) started on RTG between May 2011 and March 2012 were included. Evaluation was carried out after 6, 12, and 24months. Changes in seizure frequency were measured as the number of seizures during three months on RTG compared with a three-month baseline period. The Clinical Global Impression scale was applied to include qualitative changes in seizure severity. All but one patient had symptomatic (structural; one patient: metabolic) or cryptogenic focal or multifocal epilepsy. All had grade III drug-resistant epilepsy and cognitive deficits of different degrees. RESULTS: The retention rates were 60% after 6months, 35% after 12months, and 20% after 24months. At 12months, there were 2 responders (10%): one had a >90% seizure reduction and the other had a >50% seizure reduction. Another 5 patients were still on RTG because of minor improvements. The reasons for discontinuation in 13 patients were adverse effects (6), lack of effect (6), and both (1). Cognitive or emotional changes were the side effects that most frequently led to discontinuation. Beyond the 12-month evaluation, 3 patients were discontinued as a consequence of the FDA warning regarding retinal pigmentation and discoloration of skin and nails in patients exposed to RTG. One patient had a moderate blue-gray finger coloring. Ophthalmological changes were not discovered. CONCLUSION: Retigabine proved to be useful only for a small minority of patients in a sample of patients with particularly difficult-to-treat epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamatos/uso terapêutico , Transtornos Cognitivos/complicações , Epilepsia/tratamento farmacológico , Deficiência Intelectual/complicações , Fenilenodiaminas/uso terapêutico , Adolescente , Adulto , Cognição , Estudos de Coortes , Epilepsia/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Chemistry ; 18(30): 9321-32, 2012 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-22733693

RESUMO

Fragmentation of the γ-aminobutyric acid molecule (GABA, NH(2)(CH(2))(3)COOH) following collisions with slow O(6+) ions (v≈0.3 a.u.) was studied in the gas phase by a combined experimental and theoretical approach. In the experiments, a multicoincidence detection method was used to deduce the charge state of the GABA molecule before fragmentation. This is essential to unambiguously unravel the different fragmentation pathways. It was found that the molecular cations resulting from the collisions hardly survive the interaction and that the main dissociation channels correspond to formation of NH(2)CH(2)(+), HCNH(+), CH(2)CH(2)(+), and COOH(+) fragments. State-of-the-art quantum chemistry calculations allow different fragmentation mechanisms to be proposed from analysis of the relevant minima and transition states on the computed potential-energy surface. For example, the weak contribution at [M-18](+), where M is the mass of the parent ion, can be interpreted as resulting from H(2)O loss that follows molecular folding of the long carbon chain of the amino acid.

16.
Chemphyschem ; 12(5): 930-6, 2011 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-21370376

RESUMO

In general, radiation-induced fragmentation of small amino acids is governed by the cleavage of the C-C(α) bond. We present results obtained with 300 keV Xe(20+) ions that allow molecules (glycine and valine) to be ionised at large distances without appreciable energy transfer. Also in the present case, the C-C(α) bond turns out to be the weakest link and hence its scission is the dominant fragmentation channel. Intact ionised molecules are observed with very low intensities. When the molecules are embedded in a cluster of amino acids, a protective effect of the environment is observed. The fragmentation pattern changes: the C-C(α) bond becomes more protected and stable amino acid cations are observed as fragments of the molecular clusters. Evidently, the molecular cluster acts as a "buffer" for the excess energy, capable of rapidly redistributing excess energy and charge.


Assuntos
Glicina/química , Íons/química , Valina/química , Transferência de Energia , Ligação de Hidrogênio , Espectrometria de Massas
17.
Artigo em Inglês | MEDLINE | ID: mdl-19940334

RESUMO

In this work, we have subjected protonated nucleobases MH(+) (M = guanine, adenine, thymine, uracil and cytosine) to a range of experiments that involve high-energy (50 keV) collision induced dissociation and electron capture induced dissociation. In the latter case, both neutralisation reionisation and charge reversal were done. For the collision induced dissociation experiments, the ions interacted with O(2). In neutral reionisation, caesium atoms were used as the target gas and the protonated nucleobases captured electrons to give neutrals. These were reionised to cations a microsecond later in collisions with O(2). In choosing Cs as the target gas, we have assured that the first electron transfer process is favourable (by about 0.1-0.8 eV depending on the base). In the case of protonated adenine, charge reversal experiments (two Cs collisions) were also carried out, with the results corroborating those from the neutralisation reionisation experiments. We find that while collisional excitation of protonated nucleobases in O(2) may lead to hydrogen loss with limited probabilities, this channel becomes dominant for electron capture events. Indeed, when sampling reionised neutrals on a microsecond timescale, we see that the ratio between MH(+) and M(+) is 0.2-0.4 when one electron is captured from Cs. There are differences in these ratios between the bases but no obvious correlation with recombination energies was found.

18.
Chemphyschem ; 10(9-10): 1619-23, 2009 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-19266530

RESUMO

The results from an experimental study of bare and microsolvated peptide monocations in high-energy collisions with cesium vapor are reported. Neutral radicals form after electron capture from cesium, which decay by H loss, NH(3) loss, or N-C(alpha) bond cleavage into characteristic z(*) and c fragments. The neutral fragments are converted into negatively charged species in a second collision with cesium and are identified by means of mass spectrometry. For protonated GA (G = glycine, A = alanine), the branching ratio between NH(3) loss and N-C(alpha) bond cleavage is found to strongly depend on the molecule attached (H(2)O, CH(3)CN, CH(3)OH, and 18-crown-6 ether (CE)). Addition of H(2)O and CH(3)OH increases this ratio whereas CH(3)CN and CE decrease it. For protonated AAA ([AAA+H](+)), a similar effect is observed with methanol, while the ratio between the z(1) and z(2) fragment peaks remains unchanged for the bare and microsolvated species. Density functional theory calculations reveal that in the case of [GA+H](+)(CE), the singly occupied molecular orbital is located mainly on the amide group in accordance with the experimental results.


Assuntos
Íons/química , Peptídeos/química , Cátions/química , Césio/química , Éteres de Coroa/química , Elétrons , Espectrometria de Massas
19.
Epilepsy Behav ; 15 Suppl 1: S26-30, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19303943

RESUMO

Epilepsy has a pervasive impact on the quality of life, and thus the psychosocial well-being, of adults with an intellectual disability. Social and economical well-being appears to be affected by an increase in restrictions on activities and thus social contact. The population has very high rates of challenging behaviors and of mental illness. It is likely that these have a significant impact on epilepsy management. When populations with and without epilepsy are controlled for level of ability, no difference in prevalence of behavior or mental illness is seen between the populations. Current knowledge is limited on crucial issues such as the long-term effect of seizure disorder on mental health, quality of life, and cognition.


Assuntos
Epilepsia/complicações , Epilepsia/psicologia , Transtornos Mentais/complicações , Mudança Social , Adaptação Psicológica , Adulto , Pessoas com Deficiência/psicologia , Humanos , Inteligência , Qualidade de Vida , Estresse Psicológico/etiologia
20.
Seizure ; 18(2): 109-18, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18760938

RESUMO

Phenobarbital and primidone frequently have adverse effects on mental functions. Therefore, an attempt was made to taper barbiturates in 85 patients out of a resident population with epilepsy and intellectual disability who were selected according to clinical criteria. The objectives were to reduce the use of barbiturates, to improve the patients' cognitive and psychological state, and to reduce polypharmacy while avoiding seizure exacerbation. Four months after complete withdrawal changes in seizure frequency were assessed as well as changes in cognitive abilities, psychological state and behaviour (using the clinical global impression scale). In 13 patients the tapering failed due to complications (seizure increase in 11 patients). In 72 patients the barbiturate was completely withdrawn (mean duration of tapering: 393 days). Cognitive improvement was achieved in 17 patients (23.6%), 5 patients (6.9%) deteriorated. Seizure frequency remained unchanged in 33 patients (45.8%), in another 15 patients (20.8%) the seizure frequency decreased. Reduction in polypharmacy was obtained in 61 patients (84.7%). In an overall judgement (clinical global impression scale) of cognitive abilities AND seizure control, 25 patients (34.7%) were improved. 31 patients (43.1%) remained unchanged while 12 patients deteriorated (4 patients: impossible to judge). For statistical analysis three outcome groups were defined: the improved group (N=25), the unchanged group (N=31), and the deteriorated/failed group (N=25) consisting of the 12 deteriorated patients plus the 13 patients in whom tapering failed. Stepwise logistic regression revealed a history of an attempt to withdraw phenobarbital/primidone (p=0.017; OR 3.8), age (p=0.012) and seizure frequency (marginally significant: p=0.097) as outcome predictors. Older age was associated with better outcome. A high seizure frequency before tapering was related to good outcome, while seizure freedom and a history of failed withdrawal were associated with deterioration/failure. Outcome did not depend on duration of barbiturate therapy, dosage or serum concentration, co-medication, reduction rate, degree of intellectual disability, or epilepsy syndrome. In summary, the number of barbiturate medications has been considerably reduced, but the principal aim of the project, to relieve patients from assumed barbiturate side effects, has been achieved only in one out of four patients.


Assuntos
Anticonvulsivantes/efeitos adversos , Barbitúricos/efeitos adversos , Cognição/efeitos dos fármacos , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Deficiência Intelectual/complicações , Quimioterapia Combinada , Humanos , Inteligência/efeitos dos fármacos , Fenobarbital/efeitos adversos , Primidona/efeitos adversos , Convulsões/etiologia , Convulsões/prevenção & controle
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