New Invariant Expressions in Chemical Kinetics.

This paper presents a review of our original results obtained during the last decade. These results have been found theoretically for classical mass-action-law models of chemical kinetics and justified experimentally. In contrast with the traditional invariances, they relate to a special battery of kinetic experiments, not a single experiment. Two types of invariances are distinguished and described in detail: thermodynamic invariants, i.e., special combinations of kinetic dependences that yield the equilibrium constants, or simple functions of the equilibrium constants; and "mixed" kinetico-thermodynamic invariances, functions both of equilibrium constants and non-thermodynamic ratios of kinetic coefficients.

Quality by design applied to olanzapine and quetiapine LC-MS/MS bioanalysis.

One major challenge in quantifying drugs in biological matrices is to manage interfering compounds. A technique such liquid chromatography coupled to mass spectrometry in tandem (LC-MS/MS) is especially suitable for this application due to its high sensitivity and selectivity in detecting low concentrations of analytes in a complex system. Due to the complexity of LC-MS/MS systems, a number of experimental parameters must be optimized to provide an adequate separation and detection of the analyte. In the present work, a design of experiments approach was developed to optimize an LC-MS/MS-based bioanalytical method to extract olanzapine (OLZ) and quetiapine (QTP) from human plasma. Three steps for the optimization process were conducted: central composite face-centered design to optimize chromatographic parameters (Step 1), ionization in mass spectrometry (Step 2) and a full 32 factorial design to optimize analyte extraction conditions (Step 3). After the optimization process, resolutions and QTP and OLZ retention time (2.3 and 4, respectively) were optimum with pH of 4.7 and 85.5% of acetonitrile for the chromatographic step. Mass spectrometry optimization step provided an increase of (±50%) in the average peak area with high signal-to-noise relationship for the analytes studied. The proposed extraction method was 70% more efficient than the initial method for all drugs analyzed.

Using Quality Tools and Methodologies to Improve a Hospital's Quality Position.

The authors identify the quality tools and methodologies most frequently used by quality-positioned hospitals versus nonquality hospitals. Northeastern U.S. hospitals in both groups received a brief, 12-question survey. The authors found that 93.75% of the quality hospitals and 81.25% of the nonquality hospitals used some form of process improvement methodologies. However, there were significant differences between the groups regarding the impact of quality improvement initiatives on patients. The findings indicate that in quality hospitals the use of quality improvement initiatives had a significantly greater positive impact on patient satisfaction and patient outcomes when compared to nonquality hospitals.

The FAST-ED App: A Smartphone Platform for the Field Triage of Patients With Stroke.

BACKGROUND AND PURPOSE: The Emergency Medical Services field triage to stroke centers has gained considerable complexity with the recent demonstration of clinical benefit of endovascular treatment for acute ischemic stroke. We sought to describe a new smartphone freeware application designed to assist Emergency Medical Services professionals with the field assessment and destination triage of patients with acute ischemic stroke. METHODS: Review of the application's platform and its development as well as the different variables, assessments, algorithms, and assumptions involved. RESULTS: The FAST-ED (Field Assessment Stroke Triage for Emergency Destination) application is based on a built-in automated decision-making algorithm that relies on (1) a brief series of questions assessing patient's age, anticoagulant usage, time last known normal, motor weakness, gaze deviation, aphasia, and hemineglect; (2) a database of all regional stroke centers according to their capability to provide endovascular treatment; and (3) Global Positioning System technology with real-time traffic information to compute the patient's eligibility for intravenous tissue-type plasminogen activator or endovascular treatment as well as the distances/transportation times to the different neighboring stroke centers in order to assist Emergency Medical Services professionals with the decision about the most suitable destination for any given patient with acute ischemic stroke. CONCLUSIONS: The FAST-ED smartphone application has great potential to improve the triage of patients with acute ischemic stroke, as it seems capable to optimize resources, reduce hospital arrivals times, and maximize the use of both intravenous tissue-type plasminogen activator and endovascular treatment ultimately leading to better clinical outcomes. Future field studies are needed to properly evaluate the impact of this tool in stroke outcomes and resource utilization.

The development and validation of a method for quantifying olanzapine in human plasma by liquid chromatography tandem mass spectrometry and its application in a pharmacokinetic study.

1. A rapid method using liquid chromatography tandem mass spectrometry for the quantification of olanzapine (OLZ) in human plasma was developed and validated. Venlafaxine was used as the internal standard (IS), and the samples were extracted from 400-µL human plasma with methyl tert-butyl ether for liquid-liquid extraction. 2. Chromatography was performed using an ACE C18, 125 × 4.6-mm i.d., 5-µm column. The mobile phase consisted of water with 0.1% formic acid for solvent A and acetonitrile with 0.1% formic acid for solvent B (50 : 50 v/v) in isocratic mode. The flow rate was 1.2 mL/min. The retention times for OLZ and the IS were 0.78 and 1.04 min, respectively. Tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring was used to detect OLZ and the IS (m/z: 313.1 > 256.1 and 278.1 > 260.2, respectively). 3. No significant matrix effects were observed on OLZ and the IS retention times, and the mean recovery of OLZ was 90.08%. The assay was linear in the concentration range of 1-20 ng/mL (R(2) = 0.9976). The intra- and inter-day precision were < 11.60% and the accuracy was < 1.66%. 4. This validated method was successfully applied to a pharmacokinetic study in which 10-mg OLZ tablets were administered to healthy volunteers and their plasma OLZ levels were monitored over time. The tests showed that the OLZ test and reference drug (Zyprexa(®)) were bioequivalent, as 90% of the confidence intervals were within the 80-125% interval proposed by regulatory agencies.

Opções cirúrgicas nas malformações artério-venosas (MAV) de orelha com comprometimento cartilaginoso: relato de casos

Objetivo: As manifestações artério-venosas (MAV) são anomalias congênitas resultantes do desenvolvimento anômalo dos vasos sanguíneos. Estas podem ser de alto ou baixo fluxo, dependendo do vaso nutridor de lesão. Ao considerar MAVs de orelha, no entanto, algumas características particulares estimulam abordagem cirúrgica. Durante a fase de crescimento, obstrução do meato acústico externo, sangramentos, ulceração ou dor podem coexistir com deformidades anatômica e transtornos psicológicos. Após a fase de crescimento pode haver estabilização, e as deformidades anatômicas cartilaginosas podem ocorrer em decorrência de deficiência de desenvolvimento por alteração na vascularização do local, por efeito de massa tumoral com compressão direta na cartilagem provocando desde deformidades leves até erosões e destruição do arcabouço cartilaginoso. Serão relatados quatro casos de MAV de orelha e suas diferentes opções terapêuticas. Relato de casos: Caso 1 - OBS, 33 anos, sexo masculino, MAV extensa de orelha com episódios freqüentes de ulceração e sangramentos, tendo sido submetido a dois procedimentos de escleroterapia sem sucesso. Submetido a embolização local no dia anterior à cirurgia, com opção cirúrgica de exérese de toda MAV com preservação cutânea da parte posterior à orelha e lóbulo e todo arcabouço cartilaginoso. Para reconstrução foi feito um retalho em "cambalhota" da fáscia temporal para propiciar leito viável para então proceder à enxertia cutânea com pele parcial de face anterior de coxa. Caso 2 - CA, 22 anos, sexo masculino, MAV de orelha com comprometimento parcial de orelha com destruição de cartilagem. Procedimento cirúrgico realizado incluiu ressecção parcial e reconstrução com Medpor. Caso 3 - JV, 8 anos, sexo masculino, MAV de pólo superior de orelha. Procedimento cirúrgico realizado incluiu ressecção local com fechamento local primário com princípio cirúrgico em "estrela"...

Ressecção cirúrgica precoce de hemangiomas nasais: indicações e resultados

Objetivo: Hemangioma é o tumor vascular mais comum e a neoplasia benigna mais freqüente da infância. O potencial de involução espontânea torna o tratamento ativo das lesões controverso. Os efeitos colaterais do tratamento clínico e as deformidades causadas pelo procedimento cirúrgico devem ser analisados criticamente quando indicado como um método terapêutico. Ao considerar hemangioma nasal, no entanto, algumas características particulares estimulam abordagem cirúrgica precoce. Durante a fase proliferativa, obstrução das vias aéreas, sangramentos, ulceração ou dor podem coexistir com deformidades anatômicas e transtornos psicológicos. Após a fase proliferativa, hemangiomas nasais são particularmente lentos a regredir, em comparação com os hemangiomas de outros sítios; e mesmo durante ou após a involução, depósitos fibrogordurosos que permanecem podem causar deformidades de contorno no local da lesão. O objetivo do presente estudo foi realizar uma avaliação crítica da abordagem cirúrgica precoce definitiva para hemangioma nasal, baseado num questionário objetivo. Método: Do abril de 1997 a março de 2008, 16 pacientes com idades entre 6 meses e 13 anos de idade no momento de cirúrgia (média de 45 meses de idade) foram submetidos a ressecção cirúrgica do hemangioma nasal, realizada pelo mesmo cirurgião. Apenas 2 doentes eram do sexo masculino...

Tratamento cirúrgico das fraturas de face em pacientes pediátricos: características clínicas em um centro de trauma terciário

Objetivo: As fraturas de face na faixa etária pediátrica apresentam pequena incidência, sendo geralmente conduzidas com tratamento conservador. O objetivo do estudo é avaliar o padrão das fraturas de face, nesta faixa etária, nos casos que necessitaram de tratamento cirúrgico. Método: No período de janeiro de 2001 a dezembro de 2007, 43 pacientes com idade entre 0 a 17 anos foram submetidos a tratamento cirúrgico de fraturas da face. Foram avaliados os seguintes dados: mecanismo de trauma, idade, sexo, ossos acometidos, índice fraturas/paciente, intervalo de tempo trauma-tratamento cirúrgico, lesões associadas e métodos de osteossíntese. Para fins comparativos, os pacientes foram divididos em dois grupos: grupo A de 0 a 12 anos, e grupo B de 13 a 17 anos. Resultados: A média de idade foi de 12,4 anos (2 a 17 anos), sendo 18 (41,86%) pacientes pertecentes ao grupo A e 25 (58,14%), ao grupo B. Em relação ao sexo, 34 (79%) pacientes eram do sexo masculino (14 grupo A e 20 grupo B) e 9 (21%) do sexo feminino, sendo 4 do grupo A e 5 do grupo B. Traumas decorrentes de colisões de veículos foram os mais freqüentes, perfazendo 18 pacientes, seguidos por quedas (11), agressões físicas (7), atropelamentos (5) e ferimentos por arma de fogo em 2 casos. Lesões associadas às fraturas de face foram diagnosticadas em 17 (40%) pacientes, sendo observados TCE grave e moderado, lesões em membros superiores e inferiores, tórax, pescoço e partes moles da face. Os ossos da face acometidos foram: mandíbula em 25 vítimas, maxila em 18, zigoma em 15, fraturas naso-etmoido-orbitárias em 7, órbita em 6, osso nasal e osso frontal em 5 vítimas, totalizando um índice fraturas/paciente de 3,9. O intervalo de tempo entre o trauma e o tratamento cirúrgico foi em media de 7,2 dias (1 a 35 dias). Os métodos de fixação incluíram bloqueio intermaxilar em 8 pacientes, osteossíntese exclusiva com fios de aço em 11 pacientes, osteossíntese com parafusos...

Language brain dominance in patients with refractory temporal lobe epilepsy: a comparative study between functional magnetic resonance imaging and dichotic listening test.

PURPOSE: To identify brain dominance for language functions with DLT and correlate these results with those obtained from fMRI in patients suffering from intractable temporal lobe epilepsy. METHOD: This study reports on 13 patients who underwent pre-surgical epileptic evaluation between April and October 2004 at the Epilepsy Surgery Program, Hospital Sao Lucas, PUCRS. In DLT, dominance was assessed through a consonant-vowel task, whereas in fMRI patients performed a verb generation task. RESULTS: Our results identified a correlation between the fMRI lateralization index and the DLT ear predominance index and reply difference index (r=0.6, p=0.02; Pearson Correlation Coefficient), showing positive correlation between results obtained from fMRI and DLT. CONCLUSION: DLT was found to significantly correlate with fMRI. These findings indicate that DLT (a non-invasive procedure) could be a useful tool to evaluate language brain dominance in pre-surgical epileptic patients as it is cheaper to perform than fMRI.

Language brain dominance in patients with refractory temporal lobe epilepsy: a comparative study between functional magnetic resonance imaging and dichotic listening test

PURPOSE: To identify brain dominance for language functions with DLT and correlate these results with those obtained from fMRI in patients suffering from intractable temporal lobe epilepsy. METHOD: This study reports on 13 patients who underwent pre-surgical epileptic evaluation between April and October 2004 at the Epilepsy Surgery Program, Hospital Sao Lucas, PUCRS. In DLT, dominance was assessed through a consonant-vowel task, whereas in fMRI patients performed a verb generation task. RESULTS: Our results identified a correlation between the fMRI lateralization index and the DLT ear predominance index and reply difference index (r=0.6, p=0.02; Pearson Correlation Coefficient), showing positive correlation between results obtained from fMRI and DLT. CONCLUSION: DLT was found to significantly correlate with fMRI. These findings indicate that DLT (a non-invasive procedure) could be a useful tool to evaluate language brain dominance in pre-surgical epileptic patients as it is cheaper to perform than fMRI.

OBJETIVO: Identificar a dominância cerebral para funções de linguagem através do teste de escuta dicótica (TED) e correlacionar com os resultados de ressonância magnética funcional (RMf) em pacientes com epilepsia refratária de lobo temporal. MÉTODO: Foram estudados 13 pacientes com epilepsia refratária de lobo temporal, que realizaram avaliações pré-cirúrgicas no período de abril a outubro de 2004 no Programa de Cirurgia de Epilepsia do Hospital São Lucas da PUCRS. Realizada investigação da dominância hemisférica para linguagem através do TED Consoante-Vogal e da RMf pela geração de verbos. RESULTADOS: Verificou-se a existência de correlação entre os índices de lateralidade (RMf) e os índices de predomínio de orelha e de diferença de resposta (TED) (r=0,6, p=0,02). CONCLUSÃO: Existe correlação entre os resultados obtidos através da RMf (índice de lateralidade) e do TED (índice de predomínio de orelha e índice de diferença de resposta) em pacientes com epilepsia refratária de lobo temporal.

Object naming is a more sensitive measure of speech localization than number counting: Converging evidence from direct cortical stimulation and fMRI.

Using direct cortical stimulation to map language function during awake craniotomy is a well-described and useful technique. However, the optimum neuropsychological tasks to use have not been detailed. We used both functional MRI (fMRI) and direct cortical stimulation to compare the sensitivity of two behavioral paradigms, number counting and object naming, in the demonstration of eloquent cortical language areas. Fifteen patients with left hemisphere lesions and seven healthy control subjects participated. Patients had both preoperative fMRI at 3 T and direct cortical stimulation. Patients and controls performed object naming and number counting during fMRI at 3 T. Laterality indices were calculated from the fMRI maps for the Number-counting>Object-naming and Object-naming>Number-counting contrasts. The same number-counting and object-naming paradigms were tested during awake craniotomy and assessed for sensitivity to speech disruption. In all patients during intraoperative cortical stimulation, speech disruption occurred at more sites during object naming than during number counting. Subtle speech errors were only elicited with the object-naming paradigm, whereas only speech arrest and/or hypophonia were measured using the number counting paradigm. In both patients and controls, fMRI activation maps demonstrated greater left lateralization for object naming as compared to number counting in both frontal and temporal language areas. Number counting resulted in a more bihemispheric distribution of activations than object naming. Both cortical stimulation testing and fMRI suggest that automated speech tasks such as number counting may not fully engage putative language networks and therefore are not optimal for language localization for surgical planning.

Functional MRI of memory in the hippocampus: Laterality indices may be more meaningful if calculated from whole voxel distributions.

Lateralization of memory by functional MRI (fMRI) may be helpful for surgical planning related to the medial temporal lobe (MTL). Most fMRI memory studies have calculated lateralization indices (LI) in the MTL from suprathreshold voxels only, but the selection of threshold remains highly arbitrary. We hypothesized that LIs could be reliably extracted from the distribution of voxels encompassing all positive T statistical values, each weighted by their own statistical significance. We also hypothesized that patient LIs that are two or more standard deviations (SD) away from the control group mean LI may be more clinically relevant than LIs that are not compared to control group. Thirteen healthy subjects had memory fMRI, and five epilepsy patients had both fMRI and the intracarotid amobarbital procedure (IAP). The fMRI task consisted of encoding patterns, scenes, and words. We found that normal subjects' LIs extracted from whole weighted statistical distributions tended to lateralize to the left for words, to the right for patterns, and intermediately for scenes, consistent with previous research. Weighted LIs were less variable than those calculated from suprathreshold voxels only. Using this approach, all patients had fMRI memory lateralizations consistent with IAP results. The weighted LIs provided a more clear-cut distinction of patients from the normal group (in terms of SDs from the group mean) than the suprathreshold voxel count approach. Our results suggest that using weighted distributions can be a useful strategy for assessing memory lateralization by fMRI in the MTL.

Ressonância magnética funcional de memória: onde estamos e onde podemos chegar / Functional MRI of memory: where we are and where we can reach

INTRODUÇÃO: Ressonância functional (fMRI) é uma técnica capaz de substituir o teste de Wada como teste padrão de lateralização de memória. Atualmente, a fMRI já pode ser utilizada para estimar a lateralização de memória nos lobos temporais mediais, mas algumas variáveis devem ser tratadas de forma a garantir uma melhor qualidade dos resultados, como a intensidade do campo magnético e o paradigma utilizado.

Functional MRI (fMRI) is a promising technique for replacing the Wada test as the standard examination of memory lateralization. Currently fMRI can already be used to estimate lateralization of memory in the medial temporal lobes, but some variables should be treated to guarantee good-quality results, such as magnetic-field strength and design types.

Integrated image- and function-guided surgery in eloquent cortex: a technique report.

The ability to effectively identify eloquent cortex in close proximity to brain tumours is a critical component of surgical planning prior to resection. The use of electrocortical stimulation testing (ECS) during awake neurosurgical procedures remains the gold standard for mapping functional areas, yet the preoperative use of non-invasive brain imaging techniques such as fMRI are gaining popularity as supplemental surgical planning tools. In addition, the intraoperative three-dimensional display of fMRI findings co-registered to structural imaging data maximizes the utility of the preoperative mapping for the surgeon. Advances in these techniques have the potential to limit the size and duration of craniotomies as well as the strain placed on the patient, but more research accurately demonstrating their efficacy is required. In this paper, we demonstrate the integration of preoperative fMRI within a neuronavigation system to aid in surgical planning, as well as the integration of these fMRI data with intraoperative ECS mapping results into a three-dimensional dataset for the purpose of cross-validation.

FunctionalMRI memory Mapping for epilepsy surgery planning: a case report

Functional evaluation of memory lateralization can have an impact of epilepsy surgery for mesial temporal lobe (MTL)epilepsy. Functional MRI (fMRI) may provide non-invasive method to assist in the determinations of memory dominance. FMRI based memory mapping, however, is still not strainghforward and determining lateralization can be difficult for a number of reasons. One oustanding question relates to the influence of material type on MTL activation. To improve pre-operative memory lateralization evaluation using an event-related fMRI paradigm. This approach was designed to take into account succeful encoding and material type. We describe here the case of a patient with MTL epilepsy who inderwent memory mapping using this new functional MRI design. For each stimulus modality, we generated maps and calculated the lateralization of the activations. The patterns encoding task was associated with the most righ-lateralized MTL activity, whereas word encoding was the brain region for different stimulus modalities that follow the overall pattern found in our previous blocked-design studies. The mapping in this case was concordant with the structural imaging and electrophysiological findings

Functional variability of the human cortical motor map: electrical stimulation findings in perirolandic epilepsy surgery.

The purpose of this study was to assess the cortical representation of sensorimotor functions in patients undergoing perirolandic epilepsy surgery, focusing on somatotopy, mosaicism, and variability of function in relation to the classic motor homunculus. The authors studied 36 patients in whom intraoperative or extraoperative electrical cortical stimulation to map motor functions was performed. A computer program was devised to register electrode number, stimulation parameters, and response to each stimulus. Electrode position was represented graphically whenever a stimulus was delivered. A total of 43 maps from 36 patients were analyzed. The authors found variations in the organization of M1 (primary motor cortex) in seven patients (19.4%). Four patients (11.1%) presented mosaicism (overlapping of functional areas), two (5.6%) presented variability (inverted disposition of M1 functional areas), and one (2.8%) had both. The results of this study challenge the notion of orderly topographic relationships between the human sensorimotor functions and their representation in the primary motor cortex. These results confirm those of other studies with animals and humans using novel imaging techniques, suggesting that the motor homunculus may not always be considered a definite and absolute representation of M1.