bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of miRNA microarrays for the analysis of cancer samples with global miRNA decrease
Authors: Wu Di , Hu Yifang , Tong Stephen , Williams Bryan R.G. , Smyth Gordon K. , Gantier Michael P.
Published: May 2013

Recent studies have established that mutations or deletions in microRNA (miRNA) processing enzymes resulting in a global decrease of miRNA expression are frequent across cancers and can be associated with a poorer prognosis. While very popular in miRNA profiling studies, it remains unclear whether miRNA microarrays are suited or not to accurately detecting global miRNA decreases seen in cancers. In this work, we analyzed the miRNA profiles of samples with global miRNA decreases using Affymetrix miRNA microarrays following the inducible genetic deletion of Dicer1. Surprisingly, up to a third of deregulated miRNAs identified upon Dicer1 depletion were found to be up-regulated following standard robust multichip average (RMA) background correction and quantile normalization, indicative of normalization bias. Our comparisons of five preprocess steps performed at the probe level demonstrated that the use of cyclic loess relying on non-miRNA small RNAs present on the Affymetrix platform significantly improved specificity and sensitivity of detection of decreased miRNAs. These findings were validated in samples from patients with prostate cancer, where conjugation of robust normal-exponential background correction with cyclic loess normalization and array weights correctly identified the greatest number of decreased miRNAs, and the lowest amount of false-positive up-regulated miRNAs. These findings highlight the importance of miRNA microarray normalization for the detection of miRNAs that are truly differentially expressed and suggest that the use of cyclic loess based on non-miRNA small RNAs can help to improve the sensitivity and specificity of miRNA profiling in cancer samples with global miRNA decrease.
The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element
Authors: Fukunaga Junichi , Nomura Yusuke , Tanaka Yoichiro , Amano Ryo , Tanaka Taku , Nakamura Yoshikazu , Kawai Gota , Sakamoto Taiichi , Kozu Tomoko
Published: May 2013

AML1 (RUNX1) is a key transcription factor for hematopoiesis that binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. Aberrations in the AML1 gene are frequently found in human leukemia. To better understand AML1 and its potential utility for diagnosis and therapy, we obtained RNA aptamers that bind specifically to the AML1 Runt domain. Enzymatic probing and NMR analyses revealed that Apt1-S, which is a truncated variant of one of the aptamers, has a CACG tetraloop and two stem regions separated by an internal loop. All the isolated aptamers were found to contain the conserved sequence motif 5′-NNCCAC-3′ and 5′-GCGMGN′N′-3′ (M:A or C; N and N′ form Watson–Crick base pairs). The motif contains one AC mismatch and one base bulged out. Mutational analysis of Apt1-S showed that three guanines of the motif are important for Runt binding as are the three guanines of RDE, which are directly recognized by three arginine residues of the Runt domain. Mutational analyses of the Runt domain revealed that the amino acid residues used for Apt1-S binding were similar to those used for RDE binding. Furthermore, the aptamer competed with RDE for binding to the Runt domain in vitro. These results demonstrated that the Runt domain of the AML1 protein binds to the motif of the aptamer that mimics DNA. Our findings should provide new insights into RNA function and utility in both basic and applied sciences.
Trane/Ingersoll Rand Combines Lean and Operations Research Tools to Redesign Feeder Manufacturing Operations
Authors: Jensen John B. , Ahire Sanjay L. , Malhotra Manoj K.
Published: May 2013

Trane U.S. Inc., a brand of Ingersoll Rand, is a leading global provider of indoor comfort systems and services. It provides service, parts, and financial solutions to commercial and residential customers worldwide. In this paper, we showcase results of combining classic lean techniques, such as value stream mapping, with operations research analytics, including statistical and simulation modeling, to dramatically improve the manufacturing of a problematic feeder component assigned to a dedicated manufacturing process. We first used value stream mapping to visualize the process and develop an overall lean strategy for the manufacturing cell. We then used regression analysis to express the relationship between numerous product attributes and improvement opportunities. Finally, we developed simulation models to assess the effectiveness of process changes on cell performance under a wide range of demand and processing conditions prevalent at the plant. Process improvement recommendations presented to Trane management included (1) a redesigned material strategy, (2) a new cell layout, and (3) a one-piece product flow. In combination, these improvements facilitate a 13 percent throughput improvement, 50 percent cycle-time reduction, and higher cell efficiency that led to projected recurring savings of more than $700,000 per year.
Practice Summary: Enhancing Forecasting and Capacity Planning Capabilities in a Telecommunications Company
Authors: Álvarez-Socarrás Ada Margarita , Berrones Arturo , Moreno Guillermo J. , Rodríguez-Sarasty Jesús A. , Cabrera-Ríos Mauricio
Published: May 2013

In the constantly changing telecommunications sector, capacity planning determines the technological resources that a company must acquire and install in advance to meet highly stochastic demand. Decisions on capacity affect service levels and return on investment. Although excess capacity increases fixed costs and the risk of equipment obsolescence, shortage of capacity may result in complaints and loss of customers. We developed an integrated decision support system to aid in the annual capacity planning process at AVANTEL, a Mexican telecommunications company, which AXTEL subsequently acquired. Using artificial neural networks, inventory models, and optimization techniques, this system addresses the entire capacity planning process, including demand forecasting, capacity expansion, and equipment selection. The significant savings that AVANTEL reported may persuade other telecommunications companies to also use the system.
Automatic Dwelling Segmentation of the Buenos Aires Province for the 2010 Argentinian Census
Authors: Bonomo Flavia , Donne Diego Delle , Durán Guillermo , Marenco Javier
Published: May 2013

In planning for a population census, determining which dwellings within a census tract each enumerator must visit is a logistical challenge. This challenge, which we call the dwelling segmentation problem, generally includes a set of constraints on the enumerators’ assigned routes and various criteria regarding the homogeneity and uniformity of the segmentation solutions. In this paper, we present a computational approach to solve this problem. We successfully applied our solution, which is a substantial improvement over manual methods, to the Province of Buenos Aires in the 2010 Argentinian census.
A Decision-Making Tool for a Regional Network of Clinical Laboratories
Authors: Andrade-Pineda Jose L. , Gonzalez-R Pedro L. , Framinan Jose M.
Published: May 2013

For healthcare systems that operate in large, geographically dispersed areas, the quality of the services provided requires the effective management of a complex transportation problem. We present a decision support system to help healthcare managers improve the delivery of biological samples collected from patients in hospitals and outpatient clinics to laboratories that perform tests on them. We develop an optimization model for supporting strategic decisions on the transport of samples and the assignment of work in a large healthcare network with geographically dispersed hospitals, clinics, and testing laboratories. We embed our model in a Web-based tool to provide planners with interactive functions, enabling them to explore solutions and interactively access data to facilitate the analysis of what-if scenarios. The tool proved invaluable in helping the Andalusian Healthcare System obtain significant improvements in efficiency, quality of service, and outsourcing costs.
Scheduling Arrivals to a Stochastic Service Delivery System Using Copositive Cones
Authors: Kong Qingxia , Lee Chung-Yee , Teo Chung-Piaw , Zheng Zhichao
Published: May 2013

In this paper we investigate a stochastic appointment-scheduling problem in an outpatient clinic with a single doctor. The number of patients and their sequence of arrivals are fixed, and the scheduling problem is to determine an appointment time for each patient. The service durations of the patients are stochastic, and only the mean and covariance estimates are known. We do not assume any exact distributional form of the service durations, and we solve for distributionally robust schedules that minimize the expectation of the weighted sum of patients' waiting time and the doctor's overtime. We formulate this scheduling problem as a convex conic optimization problem with a tractable semidefinite relaxation. Our model can be extended to handle additional support constraints of the service durations. Using the primal–dual optimality conditions, we prove several interesting structural properties of the optimal schedules. We develop an efficient semidefinite relaxation of the conic program and show that we can still obtain near-optimal solutions on benchmark instances in the existing literature. We apply our approach to develop a practical appointment schedule at an eye clinic that can significantly improve the efficiency of the appointment system in the clinic, compared to an existing schedule.
Robust Partitioning for Stochastic Multivehicle Routing
Authors: Carlsson John Gunnar , Delage Erick
Published: May 2013

The problem of coordinating a fleet of vehicles so that all demand points on a territory are serviced and the workload is most evenly distributed among the vehicles is a hard one. For this reason, it is often an effective strategy to first divide the service region and impose that each vehicle is only responsible for its own subregion. This heuristic also has the practical advantage that over time, drivers become more effective at serving their territory and customers. In this paper, we assume that client locations are unknown at the time of partitioning the territory and that each of them will be drawn identically and independently according to a distribution that is actually also unknown. In practice, it might be impossible to identify precisely the distribution if, for instance, information about the demand is limited to historical data. Our approach suggests partitioning the region with respect to the worst-case distribution that satisfies first- and second-order moments information. As a side product, our analysis constructs for each subregion a closed-form expression for the worst-case density function, thus providing useful insights about what affects the completion time most heavily. The successful implementation of our approach relies on two branch-and-bound algorithms: whereas the first finds a globally optimal partition of a convex polygon into two convex subregions, the second finds a local optimum for the harder n-partitioning problem. Finally, simulations of a parcel delivery problem will demonstrate that our data-driven approach makes better use of historical data as it becomes available.
Approximation Algorithms for the Stochastic Lot-Sizing Problem with Order Lead Times
Authors: Levi Retsef , Shi Cong
Published: May 2013

We develop new algorithmic approaches to compute provably near-optimal policies for multiperiod stochastic lot-sizing inventory models with positive lead times, general demand distributions, and dynamic forecast updates. The policies that are developed have worst-case performance guarantees of 3 and typically perform very close to optimal in extensive computational experiments. The newly proposed algorithms employ a novel randomized decision rule. We believe that these new algorithmic and performance analysis techniques could be used in designing provably near-optimal randomized algorithms for other stochastic inventory control models and more generally in other multistage stochastic control problems.
Optimal Budget Allocation for Sample Average Approximation
Authors: Royset Johannes O. , Szechtman Roberto
Published: May 2013

The sample average approximation approach to solving stochastic programs induces a sampling error, caused by replacing an expectation by a sample average, as well as an optimization error due to approximating the solution of the resulting sample average problem. We obtain estimators of an optimal solution and the optimal value of the original stochastic program after executing a finite number of iterations of an optimization algorithm applied to the sample average problem. We examine the convergence rate of the estimators as the computing budget tends to infinity, and we characterize the allocation policies that maximize the convergence rate in the case of sublinear, linear, and superlinear convergence regimes for the optimization algorithm.
Technical Note—Optimal Control Policy for Capacitated Inventory Systems with Remanufacturing
Authors: Gong Xiting , Chao Xiuli
Published: May 2013

This paper studies the optimal control policy for capacitated periodic-review inventory systems with remanufacturing. The serviceable products can be either manufactured from raw materials or remanufactured from returned products; but the system has finite capacities in manufacturing, remanufacturing, and/or total manufacturing/remanufacturing operations in each period. Using L-natural convexity and lattice analysis, we show that, for systems with a remanufacturing capacity and a manufacturing/total capacity, the optimal remanufacturing policy is a modified remanufacture-down-to policy and the optimal manufacturing policy is a modified total-up-to policy. Our study reveals that the optimal policies always give production priority to remanufacturing for systems with a remanufacturing capacity and/or a total capacity; but this priority fails to hold for systems with a manufacturing capacity.
Generating Applicable Synthetic Instances for Branch Problems
Authors: Lopes Leo , Smith-Miles Kate
Published: May 2013

Generating valid synthetic instances for branch problems—those that contain a core problem like knapsack or graph coloring, but add several complications—is hard. It is even harder to generate instances that are applicable to the specific goals of an experiment and help to support the claims made. This paper presents a methodology for tuning instance generators of branch problems so that synthetic instances are similar to real ones and are capable of eliciting different behaviors from solvers. A statistic is proposed to summarize the applicability of instances for drawing a valid conclusion. The methodology is demonstrated on the Udine timetabling problem. Examples and the necessary cyberinfrastructure are available as a project from Computational Infrastructure for Operations Research (COIN-OR).
Multiarea Stochastic Unit Commitment for High Wind Penetration in a Transmission Constrained Network
Authors: Papavasiliou Anthony , Oren Shmuel S.
Published: May 2013

In this paper we present a unit commitment model for studying the impact of large-scale wind integration in power systems with transmission constraints and system component failures. The model is formulated as a two-stage stochastic program with uncertain wind production in various locations of the network as well as generator and transmission line failures. We present a scenario selection algorithm for selecting and weighing wind power production scenarios and composite element failures, and we provide a parallel dual decomposition algorithm for solving the resulting mixed-integer program. We validate the proposed scenario selection algorithm by demonstrating that it outperforms alternative reserve commitment approaches in a 225 bus model of California with 130 generators and 375 transmission lines. We use our model to quantify day-ahead generator capacity commitment, operating cost impacts, and renewable energy utilization levels for various degrees of wind power integration. We then demonstrate that failing to account for transmission constraints and contingencies can result in significant errors in assessing the economic impacts of renewable energy integration.
Low systemic testosterone levels induce androgen maintenance in benign rat prostate tissue
Authors: Zhou Ye , Otto-Duessel Maya , He Miaoling , Markel Susan , Synold Tim , Jones Jeremy O
Published: May 2013

Prostate cancer (PC) is both an age- and an androgen-dependent disease. Paradoxically, systemic levels of androgens decline with age as the risk of PC rises. While there is no correlation between systemic androgen levels and the risk of PC, systemic androgen levels do not reflect the levels of androgens in prostate tissue. In metastatic PC, changes in the androgen biosynthesis pathway during hormone therapy result in increased levels of androgens in cancer tissue and contribute to continued androgen receptor (AR) signaling. It is possible that similar changes occur in normal prostate tissue as androgen levels decline with age and that this contributes to tumorigenesis. In the present study, we sought to determine whether the rat prostate is able to maintain functional levels of androgens despite low serum testosterone levels. Rats were castrated and implanted with capsules to achieve castrate, normal, sub-physiological, and supra-physiological levels of testosterone. After 6 weeks of treatment, LC–MS/MS was used to quantify the levels of testosterone and dihydrotestosterone (DHT) in the serum and prostate tissue. Quantitative RT-PCR was used to quantify the expression of genes involved in the androgen/AR signaling axis. Despite significantly different levels of testosterone and DHT being present in the serum, testosterone and DHT concentrations in prostate tissue from different testosterone-treatment groups were very similar. Furthermore, the expression of androgen-regulated genes in the prostate was similar among all the testosterone-treatment groups, demonstrating that the rat prostate can maintain a functional level of androgens despite low serum testosterone levels. Low-testosterone treatment resulted in significant alterations in the expression of androgen biosynthesis genes, which may be related to maintaining functional androgen levels.
Hypoxia upregulates the gene expression of mitochondrial aconitase in prostate carcinoma cells
Authors: Tsui Ke-Hung , Chung Li-Chuan , Wang Shyi-Wu , Feng Tsui-Hsia , Chang Phei-Lang , Juang Horng-Heng
Published: May 2013

Hypoxia induces metabolic alteration in cancer cells by stabilizing hypoxia-inducible factor 1α (HIF-1α (HIF1A)), which regulates the bioenergetic genes of glycolysis and lipid metabolic pathways. However, the target genes of hypoxia-induced metabolic alterations in the prostate remain uncertain. Mitochondrial aconitase (mACON) (ACONM) is an enzyme that is central to carbohydrate and energy metabolism and is responsible for the interconversion of citrate to isocitrate as part of the citric acid cycle in the human prostate. We evaluated the effects of the molecular mechanisms of hypoxia onmACONgene expression in PC-3 and LNCaP human prostate carcinoma cells. Immunoblotting assays revealed that hypoxia modulated mACON and lactate dehydrogenase A (LDHA) protein expression, while these effects were attenuated whenHIF-1αwas knocked down. Hypoxia induced fatty acid synthase (FASN) in PC-3 cells while hypoxia blockedFASNgene expression in LNCaP cells after 24-h incubation. Results of real-time RT-qPCR, immunoblotting, and transient gene expression assays revealed that hypoxia treatment or co-transfection withHIF-1αexpression vector enhanced gene expression ofmACON, implying that hypoxia modulatedmACONat the transcriptional level. Hypoxia-inducedmACONpromoter activity is dependent on the DNA fragment located at −1013 to −842 upstream of the translation initiation site.l-mimosine, an iron chelator, stabilized HIF-1α but downregulatedmACONgene expression, suggesting that iron chelation blocked the hypoxia-inducedmACONgene expression. These results suggest that hypoxia dysregulates the expressions ofLDHA,FASN, andmACONgenes, and the hypoxia-inducedmACONgene expression is via the HIF-1α-dependent and iron-dependent pathways in prostate carcinoma cells.
Male pubertal development: are endocrine-disrupting compounds shifting the norms?
Authors: Zawatski William , Lee Mary M
Published: May 2013

Endocrine-disrupting compounds (EDCs) are synthetic or natural compounds that interfere with endogenous endocrine action. The frequent use of chemicals with endocrine active properties in household products and contamination of soil, water, and food sources by persistent chemical pollutants result in ubiquitous exposures. Wildlife observations and animal toxicological studies reveal adverse effects of EDCs on reproductive health. In humans, a growing number of epidemiological studies report an association with altered pubertal timing and progression. While these data are primarily reported in females, this review will focus on the small number of studies performed in males that report an association of polychlorinated biphenyls with earlier sexual maturity rating and confirm subtle effects of lead, dioxins, and endosulfan on delaying pubertal onset and progression in boys. Recent studies have also demonstrated that EDC exposure may affect pubertal testosterone production without having a noticeable effect on sexual maturity rating. A limitation to understand the effects of EDCs in humans is the potential for confounding due to the long temporal lag from early-life exposures to adult outcomes. The complex interplay of multiple environmental exposures over time also complicates the interpretation of human studies. These studies have identified critical windows of vulnerability during development when exposures to EDCs alter critical pathways and affect postnatal reproductive health. Contemporaneous exposures can also disrupt the hypothalamic–pituitary–gonadal axis. This paper will review the normal process of puberty in males and summarize human data that suggest potential perturbations in pubertal onset and tempo with early-life exposures to EDCs.
2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue
Authors: Oliva Karen , Barker Gillian , Rice Gregory E , Bailey Mark J , Lappas Martha
Published: May 2013

Gestational diabetes mellitus (GDM) is a significant risk factor for the type 2 diabetes epidemic in many populations. Maternal adipose tissue plays a central role in the pathophysiology of GDM. Thus, the aim of this study was to determine the effect of GDM on the proteome of adipose tissue. Omental adipose tissue was obtained at the time of term Caesarean section from women with normal glucose tolerance (NGT) or GDM. 2D-difference gel electrophoresis (DIGE), followed by mass spectrometry, was used to identify protein spots (n=6 patients per group). Western blotting was used for confirmation of six of the spot differences (n=6 patients per group). We found 14 proteins that were differentially expressed between NGT and GDM adipose tissue (≥1.4-fold,P<0.05). GDM was associated with an up-regulation of four proteins: collagen alpha-2(VI) chain (CO6A2 (COL6A2)), fibrinogen beta chain (FIBB (FGB)), lumican (LUM) and S100A9. On the other hand, a total of ten proteins were found to be down-regulated in adipose tissue from GDM women. These were alpha-1-antitrypsin (AIAT (SERPINA1)), annexin A5 (ANXA5), fatty acid-binding protein, adipocyte (FABP4), glutathione S-transferase P (GSTP (GSTP1)), heat-shock protein beta-1 (HSP27 (HSPB1)), lactate dehydrogenase B chain (LDHB), perilipin-1 (PLIN1), peroxiredoxin-6 (PRX6 (PRDX6)), selenium-binding protein 1 (SBP1) and vinculin (VINC (VCL)). In conclusion, proteomic analysis of omental fat reveals differential expression of several proteins in GDM patients and NGT pregnant women. This study revealed differences in expression of proteins that are involved in inflammation, lipid and glucose metabolism and oxidative stress and added further evidence to support the role of visceral adiposity in the pathogenesis of GDM.
Increased adiposity and insulin correlates with the progressive suppression of pulsatile GH secretion during weight gain
Authors: Steyn F J , Xie T Y , Huang L , Ngo S T , Veldhuis J D , Waters M J , Chen C
Published: May 2013

Pathological changes associated with obesity are thought to contribute to GH deficiency. However, recent observations suggest that impaired GH secretion relative to excess calorie consumption contributes to progressive weight gain and thus may contribute to the development of obesity. To clarify this association between adiposity and GH secretion, we investigated the relationship between pulsatile GH secretion and body weight; epididymal fat mass; and circulating levels of leptin, insulin, non-esterified free fatty acids (NEFAs), and glucose. Data were obtained from male mice maintained on a standard or high-fat diet. We confirm the suppression of pulsatile GH secretion following dietary-induced weight gain. Correlation analyses reveal an inverse relationship between measures of pulsatile GH secretion, body weight, and epididymal fat mass. Moreover, we demonstrate an inverse relationship between measures of pulsatile GH secretion and circulating levels of leptin and insulin. The secretion of GH did not change relative to circulating levels of NEFAs or glucose. We conclude that impaired pulsatile GH secretion in the mouse occurs alongside progressive weight gain and thus precedes the development of obesity. Moreover, data illustrate key interactions between GH secretion and circulating levels of insulin and reflect the potential physiological role of GH in modulation of insulin-induced lipogenesis throughout positive energy balance.
SLiM: Simulating Evolution with Selection and Linkage
Authors: Messer Philipp W
Published: May 2013

SLiM is an efficient forward population genetic simulation designed for studying the effects of linkage and selection on a chromosome-wide scale. The program can incorporate complex scenarios of demography and population substructure, various models for selection and dominance of new mutations, arbitrary gene structure, and user-defined recombination maps.
Genome Engineering ofDrosophilawith the CRISPR RNA-Guided Cas9 Nuclease
Authors: Gratz Scott J , Cummings Alexander M , Nguyen Jennifer N , Hamm Danielle C , Donohue Laura K , Harrison Melissa M , Wildonger Jill , O’Connor-Giles Kate M
Published: May 2013

We have adapted a bacterial CRISPR RNA/Cas9 system to precisely engineer the Drosophila genome and report that Cas9-mediated genomic modifications are efficiently transmitted through the germline. This RNA-guided Cas9 system can be rapidly programmed to generate targeted alleles for probing gene function in Drosophila.
Fenilcetonúria: estudo clínico e mediante biópsia cerebral
Authors: Diament Aron J. , Lefèvre Antonio B.
Published: May 2013

Foram relatados 6 casos de fenilcetonúria (oligofrenia fenilpirúvica), sendo os pacientes, irmãos dois a dois, pertencentes a três famílias distintas. Foram feitos estudos genealógico, clínico e laboratorial, incluindo a dosagem de fenilalanina sérica. O interesse maior foi o de mostrar a normalidade do estudo histopatológico realizado por meio de biópsias cerebrais em 4 casos, apesar de não ter sido feito estudo histoquímico, atualmente considerado como necessário. Esta normalidade das biópsias não teve qualquer relação com o nível mental, com as alterações eletrencefalográficas cu com atrofias cerebrais assinaladas em alguns casos mediante encefalografia gasosa. Todos os casos foram tratados com dieta especial (tipo Lofenalac) complementada com alimentos de baixo teor em fenilalanina. Dosagens de fenilalanina sérica estão sendo feitas antes e depois do uso de tais dietas, sendo ainda muito cedo para qualquer conclusão.
Convulsions in childhood: electroencephalographs aspects
Authors: Pupo Paulo Pinto , Reis Filho Isnard
Published: May 2013

The electroencephalographic records of 700 children, up to 6 years old, with a history of only convulsions without other clinical manifestations are analysed. The EEG findings in patients with febrileand non febrile convulsions,in waking and sleeping state and according to their age (0-2 and 3-6 years old), were compared statistically. From this study three main conclusions can be drawn: 1) there is a significant percentage of cerebral abnormalities among the children with isolated convulsions; 2) there is a significantly higher incidence of focal abnormalities in patients with non febrile convulsionsthan in those with febrile convulsions,suggesting that convulsions in each group may correspond to different cerebral conditions; 3) in the electroencephalographic study of these children with convulsions one must take into account the state of the patient during the recording (awake or asleep). It would be an error to consider results as they were of a homogeneous group.
Complicação rara e reversível de síndrome convulsiva: hipotonia generalizada e alterações da atividade intelectual
Authors: Lison Michel Pierre , Ribeiro M. V. Moura , Mega Décio
Published: May 2013

Os autores relatam uma síndrome hipotônica transitória com perturbações da atividade intelectual, que surgiu no decorrer da evolução de um caso de epilepsia, em criança de um ano de idade. Uma tentativa de interpretação fisiopatogênica das manifestações clínicas e eletrencefalográficas é realizada à luz dos conhecimentos atuais sobre certas disfunções reticulares e suas respectivas expressões bioelétricas.
Leptomeningite e tumor da região optoquiasmática
Authors: Silva J. A. Gonçalves da , Saraiva Sylvio , Spina-França A.
Published: May 2013

São registrados dois casos de tumores situados no assoalho da fossa craniana média (carcinoma sólido da hipófise e craniofaringeoma) acompanhados de leptomeningite de etiologia não determinada. Especialmente no segundo caso esta se caracterizava pela ocorrência de repetidos surtos de exacerbação. Em ambos o diagnóstico inicial foi de leptomeningite, tendo sido o insucesso das medidas terapêuticas adotadas que levou a estudos radiológicos, na tentativa de evidenciar focos que pudessem estar mantendo a infecção. Em ambos os casos o exame radiológico forneceu dados que permitiram orientar o diagnóstico de tumor do assoalho da fossa craniana média. As condições clínicas, no entanto, impediram que fossem adotadas em tempo útil medidas terapêuticas que visassem diretamente o tumor, vindo os pacientes a falecer. A possibilidade da ocorrência de meningites em tumores dessa região é discutida, bem como a natureza séptica ou asséptica da reação inflamatória. Os casos apresentados permitem concluir que, em processos meningíticos de evolução longa, acompanhados de surtos de agudização, nos quais nem mesmo durante os surtos agudos é encontrado o agente etiológico no LCR, a possibilidade da ocorrência de tumores do assoalho da fossa média do crânio deve ser estudada. O estudo deve ser feito precocemente, para permitir a adoção de medidas terapêuticas adequadas, visando diretamente o tumor, em tempo hábil, na tentativa de evitar que os surtos meningíticos venham a comprometer a vida do paciente.
Diagnóstico diferencial das distrofias musculares com referência especial às alterações enzimáticas
Authors: Heick H. , Laudahn G.
Published: May 2013

Depois de apresentar os dados clínicos e genéticos relativos a 221 casos de distrofia muscular progressiva (125 casos do tipo Duchenne, 63 do tipo cintura pélvica e 25 do tipo fácio-escápulo-umeral), os autores analisam os resultados das dosagens sôro-enzimáticas que fizeram; em alguns casos foram pesquisas também as atividades de 25 enzimas em homogeneizados de tecido muscular. Os mesmos exames foram feitos em casos de miopatias de outra etiologia e de distrofias musculares neuropáticas e mielopáticas. Foi verificado que o teor das sôro-enzimas aumenta em todas as formas de distrofia muscular progressiva hereditária. No tipo Duchenne as-atividades enzimáticas são elevadas desde o nascimento das crianças acometidas, precedendo o aparecimento da sintomatologia clínica. Com o progredir da moléstia e com o decorrer dos anos os teores sôro-enzimáticos tendem a diminuir, podendo reduzir-se aos valores normais nas fases finais da moléstia. No tecido muscular não existe diferença significante, no que respeita à composição enzimática, entre os diversos tipos de distrofia muscular progressiva e hereditária. Com exceção de poucas enzimas cuja atividade é maior nos tecidos conjuntivo e adiposo que progressivamente substituem o tecido muscular que entra em atrofia, o teor das mio-enzimas diminui com o progredir da moléstia, como expressão do crescente esgotamento do citoplasma da célula muscular. Nas distrofias musculares neuropáticas e mielopáticas as alterações são idênticas, embora de menor intensidade. Algumas diferenças quantitativas podem ser explicadas pela idade dos pacientes e pela intensidade do processo. A mesma diferença pode ser demonstrada mediante exames histopatológicos: nas formas que acometem crianças (Werdnig-Hoffmann) as fibras musculares ainda não denervadas se apresentam com aspecto normal, ao passo que, nas formas do adulto (Kugelberg-Welander), possivelmente pelo desgaste provocado pelos esforços musculares, tais fibras freqüentemente apresentam alterações idênticas às encontráveis nas distrofias musculares miopáticas hereditárias.
Espasmos em flexão: estudo clínico e eletrencefalográfico de pacientes tratados com Ro 4-5360
Authors: Lison P. , Mega Décio
Published: May 2013

Sete pacientes com espasmos em flexão não controlados com medicações anticonvulsivas usuais foram submetidos a tratamento com Ro 4-5360 (Mogadon), à razão de 5 a 10 mg por dia. Foram discutidos os resultados clínicos e os achados eletrencefalográficos. Especial ênfase foi dedicada às correlações eletroclínicas. Os autores concluem: 1) Houve redução rápida e significativa na intensidade e na freqüência dos surtos de espasmos em flexão em todos os casos tratados com Mogadon. 2) Os melhores resultados foram observados em crianças que apresentavam desenvolvimento psicomotor normal até o aparecimento dos espasmos em flexão. 3) O intervalo entre o início dos espasmos em flexão e o início do tratamento com Mogadon e o insucesso de tratamentos anteriores com ACTH não foram fatores desfavoráveis quanto aos resultados da terapêutica benzcdiazepínica. 4) Houve ligeira regressão do retardo psicomotor, em 5 dos 7 casos, não acompanhando a nítida melhora das manifestações convulsivas, melhora cuja precocidade e intensidade foram mais acentuadas nas crianças em que o desenvolvimento psicomotor era inicialmente normal. 5) Nos casos que apresentavam hipsarritmia, houve desaparecimento da manifestação ao fim de uma semana de tratamento. 6) O aparecimento de sincronização rápida por espículas de amplitude uniforme e de topografia difusa no eletrencefalograma, dos pacientes tratados com Mogadon, parece ser função da incidência de elementos rápidos de tipo irritativo nos traçados realizados antes do tratamento. 7) Na vigência do aparecimento da sincronização por espículas difusas surgiram crises tônicas generalizadas em duas crianças que não apresentavam este tipo antes do tratamento, sendo de notar que essas manifestações eletrencefalográficas e clínicas diminuíram ulteriormente e desapareceram após três meses de tratamento. 8) Em três casos, passada a fase de alterações paroxisticas difusas, permaneceram anomalias focais, apontando para possível "ponto de impacto" inicial da agressão cerebral, de acordo com o conceito de Vallat e Lepetit.
Riso na epilepsia
Authors: Jardim Edymar , Armbrust-Figueiredo Jorge
Published: May 2013

São estudados três casos de síndrome convulsiva temporal, com manifestações concomitantes de riso na sua fase inicial. As características principais foram a imotivação e á incoercibilidade do riso. Esses sintomas desapareceram com o uso de anticonvulsivantes.
Alterações funcionais da junção neuromuscular provocadas em ratos pela administração diária e prolongada de um agente curarizante
Authors: Zanini Antonio Carlos
Published: May 2013

A ratos adultos, machos, foi administrado durante 8 semanas, uma vez ao dia, o iodeto do dimetiléter da d-tubocurarina (DMT), pela via intraperitoneal. Os animais foram distribuídos em 3 lotes: os do 1.°, receberam 5,5 gama de DMT/kg/dia; os do 2.°, 16,6 gama/kg/dia; os do 3.° (controle), 1 ml da solução isotônica de cloreto de sódio. A força muscular dos animais foi avaliada uma vez por semana, de acordo com o método descrito no texto, antes e após a injeção intraperitoneal da referida substância. Com o decorrer da experimentação, observou-se que: a) houve diminuição significativa da força muscular dos animais, avaliada após esvaecimento da atividade curarizante do DMT; b) a determinação da força muscular, feita logo após a injeção, mostrou que a dose de 5,5 gama/kg/dia provoca um aumento da suscetibilidade dos animais à ação curarizante do DMT; c) o efeito inibidor provocado pela dose de 16,6 gama/kg/dia de DMT aumentou no início mas diminuiu significantemente após a 5ª semana, muito embora houvesse uma progressiva diminuição da força muscular, sugerindo independência entre os dois efeitos. Com base nesses resultados, são discutidos alguns fenômenos que podem ocorrer na instalação e tratamento da miastenia grave.
Ensaio clínico com novo psicotrópico (P-4657B) em pacientes hospitalizados
Authors: Signorini Jamil , Vieira Nelson Cortez , Marques-Assis Luís , Martins Clovis
Published: May 2013

É experimentado um novo psicotrópico — o P-4657B (Thiothixene) — em 14 doentes mentais crônicos (12 esquizofrênicos, um débil mental e um com depressão involutiva). O medicamento foi utilizado em doses que variaram entre 20 e 75 mg/dia, em período que oscilou entre 22 e 130 dias. Em um caso houve piora da sintomatologia; melhoras ocorreram em 5 casos, dois dos quais obtiveram alta experimental. No que se refere aos sintomas, melhores resultados foram obtidos em relação ao contato e à capacidade pragmática. Não foram notados efeitos colaterais severos, tendo sido verificadas manifestações neurodislépticas, discretas, em apenas três casos, sem relação com a dose empregada. Os autores concluem ser o Thiothixene um psicotrópico útil na terapêutica de doentes mentais crônicos, especialmente de esquizofrênicos nos quais predominem a deficiência de contato e o apragmatismo e sugerem a experimentação desse medicamento em psicoses agudas.
Sobressalto patológico: aspectos clínicos e eletrencefalográficos
Authors: Kliemann Frederico Dahne , Ferreira Nelson Pires
Published: May 2013

Os autores relatam o caso de um paciente apresentando crises de sobressalto provocadas por estímulos auditivos, sensitivos e visuais, sem crises epilépticas espontâneas nem retardo psicomotor. Estudam os aspectos clínicos e eletrencefalográficos e revisam a situação da entidade entre as assim chamadas epilepsias reflexas.
Meningioma em placa atingindo toda a convexidade cerebral
Authors: Almeida M. de , Salum Jamil , Mantovani Cleusa M. , Marcondes Marcelo
Published: May 2013

É apresentado caso de extenso meningioma em placa atingindo toda a convexidade e determinando grande hiperostose da calota craniana. O quadro clínico caracterizou-se por aumento do volume do crânio, cefaléia, déficit de visão e convulsões. As radiografias e o estudo necroscópico mostraram que as tábuas ósseas foram substituídas por espículas dispostas radialmente. O aspecto histológico, típico de meningioma, não sugeria malignidade.
Alterações cerebelares em pacientes com cardiopatia crônica chagásica
Authors: Alencar Alexandre
Published: May 2013

Foram estudados 12 cerebelos de pacientes com cardiopatia crônica chagásica, 9 cerebelos de pacientes com cardiopatias não chagásicas (ambos os grupos constituídos de indivíduos falecidos em fase de insuficiência cardíaca congestiva) e dois cerebelos de indivíduos normais, falecidos acidentalmente. Nos pacientes chagásicos foi verificada redução numérica nas células de Purkinje, alterações de natureza regressiva nas células remanescentes, alterações das cestas peripurkinjeanas e mobilização microglial. Estas modificações foram também encontradas nos cerebelos dos cardiopatas não chagásicos. As alterações observadas foram interpretadas como resultantes da hypoxemia do sistema nervoso central devido à falência cardíaca.
Alterações quantitativas das células de purkinje na moléstia de chagas experimental no camundongo
Authors: Jardim Edymar
Published: May 2013

O autor estudou quantitativamente as células de Purkinje em cortes semi-seriados do cerebelo de camundongos inoculados experimentalmente com T. cruzi,tendo verificado considerável destruição neuronal na fase aguda da enfermidade.
Aspectos histoquímicos do plexo mientérico na doença de chagas experimental
Authors: Sena Plínio Garcez de , Teles Filho Moysés
Published: May 2013

Foi comparada, na doença de Chagas experimental em ratos brancos, a atividade esterásica entre animais infectados e animais de um grupo controle. Do ponto de vista histológico ocorreram poucas alterações no plexo de Auerbach. Entretanto, a evidente diminuição da atividade esterásica parece demonstrar que os animais infectados perdem, mesmo antes da ocorrência de lesões histológicas, a citada atividade enzimática.
A metisergide no tratamento da epilepsia temporal
Authors: Armbrust-Figueiredo Jorge
Published: May 2013

A metisergide (butanolamida do ácido 1-metil-lisérgico) foi empregada experimentalmente em 78 pacientes com epilepsia psicomotora e com alterações focais (ondas "sharp") de projeção em um dos lobos temporais, no EEG. Foram usadas doses diárias de 2 a 6 mg, associadas a 0,1 g de fenobarbital. Dos 78 pacientes, 59 responderam de maneira favorável ao tratamento, sendo que 47 deixaram de sofrer crises e 12 apresentaram diminuição acentuada da freqüência e intensidade das crises. As manifestações psíquicas também melhoraram com o tratamento, ao contrário do que geralmente acontece com outras drogas. As alterações eletrencefalográficas desapareceram ou melhoraram em 64% dos pacientes. Reações secundárias ocorreram em 39 dos pacientes, na fase inicial do tratamento, e foram de curta duração, desaparecendo espontâneamente.
Ultrassom focalizado: nova arma terapêutica na cirurgia estereotáxica
Authors: Marino Jr. Raul
Published: May 2013

O autor faz um apanhado das teorias fundamentais do ultrassom focalizado e seu uso em cirurgia estereotáxica cerebral. É feita análise comparativa entre as vantagens do ultrassom frente às demais técnicas de lesão estereotáxica e são considerados os dados de importância quanto ao tipo de apralehagem empregada e o modo de sua utilização. Como ilustração de suas possibilidades práticas, são referidas as aplicações deste tipo de irradiação no tratamento do parkinsonismo, de hipercinesias, da neuralgia do trigêmeo, de neuromas de amputação e da síndrome de Menière, na prática de comissurotomias e de lobotomias pré-frontais, na obtenção de lesões em trabalhos experimentais.
Comentários neurocirúrgicos e fisiológicos sobre a secção da haste pituitária em seres humanos (miscotomia)
Authors: Le Beau J. , Foncin J. F. , Nicolaidis S.
Published: May 2013

Nossa primeira hipofisectomia para tratamento de carcinoma metastático do seio foi feita em novembro de 1951 e a secção da haste pituitária (miscotomia) para o mesmo fim foi iniciada em novembro de 1956. Quando se consegue impedir a regeneração vascular hipotálamo-hipofisária os resultados gerais da miscotomia são pouco diferentes daqueles obtidos com a hipofisectomia. Empregamos a miscotomia sempre que, por condições locais ou gerais, a remoção total da hipófise parece constituir grande risco cirúrgico. Temos publicado estudos anatomo-fisiológicos desde 1958 mostrando: (a) as variações da necrose do lobo anterior da hipófise que não são totais nem definitivas (regeneração pituitária) e a importância das artérias trabeculares a este respeito; b) a grande capacidade de regeneração vascular a partir do hipctálamo e dirigindo-se para a parte restante do lobo anterior da hipófise, o que constitui um novo sistema anatomo-funcional portal; c) após isolamento permanente da pituitária ocorre proliferação das células de prolactina (células orangeófilas) e hipertrofia compensadora da pars tuberalis. A remoção cirúrgica de tecido hipofisário normal nos permitiu descrever, pela primeira vez no ser humano, as células ACTH (1964) e as células FSH (1966).
Subacute sclerosing leucoencephalitis: an epidemiological, clinical and biochemical study of 31 cases
Authors: Canelas Horácio M. , Juliäo O. Freitas , Lefèvre Antônio B. , Assis J. Lamartine de , Tognola Waldir A. , Jorge Francisco B. de , Fonseca Lineu C. , Xavier-Lima A.
Published: May 2013

Thirty-one cases of SSLE are reported. The diagnosis was based on the clinical picture, the marked increase of gammaglobulins in the cerebrospinal fluid, the typical electroencephalographic pattern, and the pathological examination. Intracellular inclusion bodies were found at the postmortem examination of 8 among 13 cases and in 1 of 7 cerebral biopsies. The mean age was 11.7 years, with the limits of 3 and 22 years. Males prevailed markedly over females (23:8). Patients from rural regions were the bulk of the series (77.4%). No definite regional predominance was demonstrated by the analysis of the geographic distribution. A seasonal influence was not evidenced. In 16 patients followed up to death, the average duration of the disease was 7 months, with a range from 2 to 20 months. In the clinical picture the constancy of myoclonus or losses of tonus, and psychiatric disorders was evidenced. The first symptom was the psychiatric alteration in 55.6% of the cases, myoclonus in 35.5% and grand mal seizures in 33.3%. Rigidity and pyramidal signs were very frequent, while the cerebellar syndrome was rare. Ophtalmoscopic alterations (edematous or pale disk, choroidits) were found in a third of the cases. In two cases an epizootic of household chicken was coincident with the onset of the disease. The blood copper concentrations determined in 8 cases were always above the normal range, while ceruloplasmin remained within the normal limits. The blood sulfur levels were high in 3 patients studied. The blood magnesium levels were variable in 6 patients studied.