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In the late years, the use of acellular dermal matrix (ADM) has extended rapidly in the field of breast reconstruction. However, with the follow-up visits, we discovered some deformities on the lateral part of the lower pole, due to the folding of the ADM. The aim of this letter is to share some tricks developed in our clinical practice that would permit the surgeon to avoid getting these irregularities in the aesthetic result of breast reconstruction with ADM. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Derme Acelular , Implantes de Mama , Mamoplastia/métodos , HumanosRESUMO
BACKGROUND: Recent trials have shown hydroxyethyl starch (HES) solutions increase the risk of acute kidney injury (AKI) in critically ill patients. It is uncertain whether these adverse effects also affect surgical patients. We sought to determine the renal safety of modern tetrastarch (6% HES 130/0.4) use in cardiac surgical patients. METHODS: In this multicentre prospective cohort study, 1058 consecutive patients who underwent cardiac surgery from 15th September 2012 to 15th December 2012 were recruited in 23 Spanish hospitals. RESULTS: We identified 350 patients (33%) administered 6% HES 130/0.4 intraoperatively and postoperatively, and 377 (36%) experienced postoperative AKI (AKI Network criteria). In-hospital death occurred in 45 (4.2%) patients. Patients in the non-HES group had higher Euroscore and more comorbidities including unstable angina, preoperative cardiogenic shock, preoperative intra-aortic balloon pump use, peripheral arterial disease, and pulmonary hypertension. The non-HES group received more intraoperative vasopressors and had longer cardiopulmonary bypass times. After multivariable risk-adjustment, 6% HES 130/0.4 use was not associated with significantly increased risks of AKI (adjusted odds ratio 1.01, 95% CI 0.71-1.46, P=0.91). These results were confirmed by propensity score-matched pairs analyses. CONCLUSIONS: The intraoperative and postoperative use of modern hydroxyethyl starch 6% HES 130/0.4 was not associated with increased risks of AKI and dialysis after cardiac surgery in our multicentre cohort.
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Injúria Renal Aguda/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Derivados de Hidroxietil Amido/efeitos adversos , Injúria Renal Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Terapia de Substituição RenalRESUMO
A randomized controlled trial was performed in 17 Colombian dairy herds to determine the cure risk among cows subclinically infected with Streptococcus agalactiae exposed to 2 antibiotic therapies. Composite milk samples were collected before milking at the onset of the trial (pretreatment) and 2 subsequent times over a period of approximately 63 d. The intramammary application (IMM) of ampicillin-cloxacillin was compared with the intramuscular application (IM) of penethamate hydriodide, and cure risks after an initial and retreatment application were assessed. Cure risk after the initial treatment was higher (82.4%) for the IMM treatment than for IM therapy (65.8%). However, no difference was observed in the cure risk of refractory cases after retreatment (IMM=52.6% vs. IM=51.2%). The cumulative cure risk (both initial and retreatment) was 90.4 and 82.9% for the IMM and IM products, respectively. A 2-level random effects logistic model that controlled for pretreatment cow-level somatic cell count, indicated that IM treatment (odds ratio=0.37) had a lower cure risk than IMM and a tendency for a lower cure risk with increasing baseline somatic cell count. Our findings suggest that both products and administration routes can reduce the prevalence of S. agalactiae in affected herds, but the IMM product had a better efficacy in curing the infection. In addition to the treatment protocol, the cow somatic cell count should be considered when making management decisions for cows infected with S. agalactiae.
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Antibacterianos/administração & dosagem , Mastite Bovina/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Ampicilina/administração & dosagem , Animais , Bovinos , Contagem de Células/veterinária , Cloxacilina/administração & dosagem , Colômbia , Feminino , Injeções Intramusculares/veterinária , Penicilina G/administração & dosagem , Penicilina G/análogos & derivados , Penicilina G/uso terapêutico , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/isolamento & purificaçãoRESUMO
INTRODUCTION: the aim of this study is to test the encoding deficit hypothesis in Alzheimer disease (AD) using a recent method for correcting memory tests. To this end, a Spanish-language adaptation of the Free and Cued Selective Reminding Test was interpreted using the Item Specific Deficit Approach (ISDA), which provides three indices: Encoding Deficit Index, Consolidation Deficit Index, and Retrieval Deficit Index. METHODS: We compared the performances of 15 patients with AD and 20 healthy control subjects and analysed results using either the task instructions or the ISDA approach. RESULTS: patients with AD displayed deficient encoding of more than half the information, but items that were encoded properly could be retrieved later with the help of the same semantic clues provided individually during encoding. Virtually all the information retained over the long-term was retrieved by using semantic clues. Encoding was shown to be the most impaired process, followed by retrieval and consolidation. Discriminant function analyses showed that ISDA indices are more sensitive and specific for detecting memory impairments in AD than are raw scores. CONCLUSIONS: These results indicate that patients with AD present impaired information encoding, but they benefit from semantic hints that help them recover previously learned information. This should be taken into account for intervention techniques focusing on memory impairments in AD.
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Doença de Alzheimer/psicologia , Transtornos da Memória/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Transtornos da Memória/etiologia , Rememoração Mental , Testes Neuropsicológicos , Semântica , Aprendizagem VerbalRESUMO
INTRODUCTION: Medical simulation is associated with intense emotions which influence human behavior. We aim to investigate how prebriefing impacts on learners' emotions during a high-fidelity simulation (HFS) session. METHODS: This is a prospective randomized controlled study. Participants were randomly allocated to receive a standardized prebriefing (SP group) versus not receiving it (NSP group). Debriefing following the «good judgment¼ approach, structured in reactions, understanding and summary phases, was used in both groups. In order to assess emotions, we used the circumplex model of affect applying the Affect Grid scale, which was performed prior to prebriefing, following case performance and following debriefing. Debriefing times were also assessed. RESULTS: A total of 128 physicians participate in the study (64 vs. 64). Following case performance, this HFS session was experienced with significantly more pleasant emotions compared to baseline, that were maintained during debriefing (pâ¯<â¯0.01) while alertness increased after case performance diminishing after debriefing (pâ¯<â¯0.01). There were no statistical significant differences between groups. In the NSP group, total debriefing (pâ¯=â¯0.003) and understanding phase (pâ¯=â¯0.002) times were significantly longer. CONCLUSIONS: This HFS session was experienced as pleasant with high alertness with no specific emotional impact attributable to prebriefing. Prebriefing leads to a freer flowing debriefing.
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INTRODUCTION: Patients with SARS-CoV-2 infection may present cardiovascular involvement including myocarditis, arrhythmias and QT interval prolongation. Our objective was to evaluate the impact of COVID-19 and its treatment on ventricular repolarization and development of arrhythmias in critically ill patients. METHODS: Retrospective cohort study of critically ill COVID-19 patients during a 3-month period in whom at least one ECG was available. Relevant clinical data and specific treatment administered for COVID-19 were recorded. Prolonged QTc was considered prolonged when it measured ≥ 460â¯ms in women and ≥450â¯ms in men. The incidence and type of arrhythmias during the same period were recorded. RESULTS: A total of 77 patients with a mean age of 62⯱â¯13 years, 20 women and 57 men, were evaluated. Sixty percent of the patients were hypertensive, 52% had a BMI > 30, and 70% developed acute renal failure during admission. Some 56% of the patients presented QTc prolongation. Forty-four percent presented some type of arrhythmia during their stay in the ICU, 21% of which were atrial arrhythmias. Overall mortality was 53%, with no differences between patients with or without prolonged QTc. CONCLUSIONS: In our series, a high proportion of critical patients with COVID-19 presented prolonged QTc and arrhythmias. The factors involved have been related to the elevation of cardiac biomarkers, the myocardial involvement of the virus and concomitant medication received in the ICU.
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COVID-19 , Síndrome do QT Longo , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , COVID-19/complicações , COVID-19/epidemiologia , Estudos de Coortes , Estudos Retrospectivos , Estado Terminal , Pandemias , Prevalência , SARS-CoV-2 , Síndrome do QT Longo/epidemiologia , Síndrome do QT Longo/complicações , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/etiologiaRESUMO
⢠The activation of high-affinity root transport systems is the best-conserved strategy employed by plants to cope with low inorganic phosphate (Pi) availability, a role traditionally assigned to Pi transporters of the Pht1 family, whose respective contributions to Pi acquisition remain unclear. ⢠To characterize the Arabidopsis thaliana Pht1;9 transporter, we combined heterologous functional expression in yeast with expression/subcellular localization studies and reverse genetics approaches in planta. Double Pht1;9/Pht1;8 silencing lines were also generated to gain insight into the role of the closest Pht1;9 homolog. ⢠Pht1;9 encodes a functional plasma membrane-localized transporter that mediates high-affinity Pi/H⺠symport activity in yeast and is highly induced in Pi-starved Arabidopsis roots. Null pht1;9 alleles exhibit exacerbated responses to prolonged Pi limitation and enhanced tolerance to arsenate exposure, whereas Pht1;9 overexpression induces the opposite phenotypes. Strikingly, Pht1;9/Pht1;8 silencing lines display more pronounced defects than the pht1;9 mutants. ⢠Pi and arsenic plant content analyses confirmed a role of Pht1;9 in Pi acquisition during Pi starvation and arsenate uptake at the root-soil interface. Although not affecting plant internal Pi repartition, Pht1;9 activity influences the overall Arabidopsis Pi status. Finally, our results indicate that both the Pht1;9 and Pht1;8 transporters function in sustaining plant Pi supply on environmental Pi depletion.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteínas de Transporte de Fosfato/metabolismo , Fosfatos/metabolismo , Fósforo/deficiência , Raízes de Plantas/metabolismo , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/genética , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Arseniatos/toxicidade , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas/genética , Fenótipo , Proteínas de Transporte de Fosfato/genética , Fósforo/farmacologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Plantas Geneticamente Modificadas , Simportadores de Próton-Fosfato/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismoRESUMO
BACKGROUND: Although without a widespread popularity, the septocutaneous gluteal artery perforator flap (sc-GAP) can be an excellent choice in breast reconstruction. The purpose of the article is to further study the preoperative imaging anatomy and surgical technique for a safe operation. PATIENTS AND METHODS: A clinical experience in four unilateral breast reconstructions is reported, and an analysis is made of the computed tomography angiography (CTA) variables (36 studies/72 sides) that might define the microsurgical consistency and reliability of the technique. RESULTS: After a careful preoperative imaging evaluation, the surgical operation confirmed a predictable, although not straightforward, anatomy. All the flaps were raised in the supine position. With a remarkably quick postoperative recovery, the resulting scar was well hidden and did not significantly distort the gluteal aesthetics although contralateral contouring liposuction might be desirable in unilateral cases. Good aesthetic results were obtained in all the patients. In the evaluation of the CTA studies, a right/left septocutaneous perforator arising from the superficial branch of the superior gluteal artery could be found in 80.6% of the patients, with a few patients having 2-3 perforators on one side. Although with an overall suitable pedicle length (mean 7.4 cm), the arterial diameter at the suture site was found to be small (mean 1.6 mm). CONCLUSION: Given the adequate body habitus and reconstructive requirements, the sc-GAP can be a good choice even in large breasts. However, the technique requires the appropriate surgical expertise and mandates a thorough preoperative imaging evaluation that defines whether the technique should be done in a particular patient.
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Artérias , Nádegas , Cicatriz , Angiografia por Tomografia Computadorizada/métodos , Mamoplastia , Retalho Perfurante , Complicações Pós-Operatórias , Adulto , Anatomia Regional/métodos , Artérias/diagnóstico por imagem , Artérias/cirurgia , Nádegas/irrigação sanguínea , Nádegas/diagnóstico por imagem , Nádegas/cirurgia , Cicatriz/diagnóstico , Cicatriz/etiologia , Diagnóstico por Imagem/métodos , Estética , Feminino , Humanos , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Avaliação de Resultados em Cuidados de Saúde , Seleção de Pacientes , Retalho Perfurante/irrigação sanguínea , Retalho Perfurante/transplante , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodosRESUMO
Recently, it has been suggested that tranexamic acid should be administered only in those patients with hyperfibrinolysis determined using viscoelastic assays, as severely injured patients may present with fibrinolytic shutdown. However the last European guidelines on management of major bleeding and coagulopathy following trauma endorse the use of tranexamic acid to the trauma patient who is bleeding or at risk of significant hemorrhage as soon as possible without waiting for viscoelastic results. We present a severely blunt trauma patient treated with on-scene administration of tranexamic acid that developed immediate pulmonary embolism.
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Antifibrinolíticos , Transtornos da Coagulação Sanguínea , Ácido Tranexâmico , Antifibrinolíticos/uso terapêutico , Fibrinólise , Hemorragia/induzido quimicamente , Humanos , Ácido Tranexâmico/uso terapêuticoRESUMO
Recently, it has been suggested that tranexamic acid should be administered only in those patients with hyperfibrinolysis determined using viscoelastic assays, as severely injured patients may present with fibrinolytic shutdown. However the last European guidelines on management of major bleeding and coagulopathy following trauma endorse the use of tranexamic acid to the trauma patient who is bleeding or at risk of significant hemorrhage as soon as possible without waiting for viscoelastic results. We present a severely blunt trauma patient treated with on-scene administration of tranexamic acid that developed immediate pulmonary embolism.
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BACKGROUND/AIMS: Cognitive dysfunction is a major handicap in multiple sclerosis (MS). Its prevalence varies due to disease heterogeneity and methodological issues. A neuropsychological battery of intermediate size was designed for and explored in the screening of cognitive dysfunction in MS patients. METHODS: The battery was administered to a hospital-based sample of 191 MS patients and 50 matched controls. Eleven test scores measuring verbal fluency, verbal learning, attention, calculation and visuoperceptual ability were selected on the basis of sensitivity and lack of redundancy. Two alternative approaches were compared for diagnosis of cognitive dysfunction based, firstly, on the number of failed tasks, and secondly, on a single standardized global score. RESULTS: The approach based on the number of failed tasks discriminated better than did the global approach between patients and controls. Using a cutoff of two altered scores, a cognitive dysfunction prevalence of 34% was obtained. The score yielded after summing errors in all tests was the most frequently altered and proved particularly useful for detecting minimally impaired patients. CONCLUSION: The purpose-designed battery was adequate for the screening of cognitive dysfunction in MS patients. The better accuracy of the single-task approach might reflect MS heterogeneity.
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Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Esclerose Múltipla/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , PrevalênciaRESUMO
INTRODUCTION: The emotional environment created during a simulation session can influence learning. Positive emotions improve perceptual processing and facilitate learning, while negative emotions can reduce working memory, resulting in poorer learning outcomes. OBJECTIVES: The aim of this study was to investigate the impact of simulation training on emotions during all phases of a high-fidelity simulation using standard prebriefing and «good judgement debriefing ¼ techniques. METHODS: This was an observational study that included 74 anesthesiologists participating in a simulation-based training. A standardized prebriefing was followed by «good judgement debriefing¼. In order to assess emotions, we used the circumplex model of emotion, and asked participants to complete the affect grid scale before prebriefing (Stage 1), before starting the simulation (Stage 2), before debriefing (Stage 3) and following debriefing (Stage 4). RESULTS: The affect grid scores obtained from 67 participants were analyzed. Following debriefing, the experience of the polytrauma patient simulation was significantly more pleasant compared to previous stages (P<0.01). In addition, participants perceived the activity as becoming increasingly active as it progressed (P<0.01). CONCLUSIONS: High-fidelity trauma simulation creating a safe environment using a standardized prebriefing and «good judgement debriefing¼ is experienced as a pleasant and active activity at all stages of the simulation. Further investigation is needed to assess the impact of these results on learning.
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Anestesiologistas/psicologia , Emoções , Traumatismo Múltiplo/psicologia , Treinamento por Simulação/métodos , Cuidados de Suporte Avançado de Vida no Trauma/psicologia , Análise de Variância , Anestesiologistas/educação , Humanos , Traumatismo Múltiplo/terapia , SensaçãoRESUMO
Late-onset neurological disease has rarely been reported in patients with glutaryl-CoA dehydrogenase (GCDH) deficiency. We present two siblings with GCDH deficiency. One of them presented with the classic neurological disease (patient 1). Routine investigation of family members revealed that her apparently unharmed 13-year-old sister was also affected (patient 2). Patient 2 started to have academic difficulties in the months prior to our assessment. Her clinical examination was normal, with the exception of a cranial circumference of 57 cm (slightly over the 98 th centile). A severe leukoencephalopathy was demonstrated on MRI. Neuropsychological assessment showed an IQ within the normal-low range and a mild impairment of memory and executive function. Previous reports on late-onset neurological disease in GCDH deficiency have revealed that progressive leukoencephalopathy develops over time. Following the recently published guideline for the diagnosis and management of GCDH deficiency, both patients are receiving dietary treatment in combination with L-carnitine supplementation. We emphasize the need to search for chronic neurological changes of late-onset type in apparently unaffected GCDH deficiency cases diagnosed in routine family investigations.
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Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/patologia , Glutaril-CoA Desidrogenase/deficiência , Adolescente , Carnitina/uso terapêutico , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Memória , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/patologia , Neurologia/métodos , Testes NeuropsicológicosRESUMO
Leukemia inhibitory factor (LIF) is a cytokine that shows conflicting effects on in vitro produced (IVP) bovine embryos. Bovine LIF (bLIF) has been cloned and used in culture, but there is no commercially available bLIF. Thus, researchers use human LIF (hLIF) to supplement the culture medium for bovine embryos because of its greater sequence homology compared to murine LIF (mLIF). We compared the effects of mLIF and hLIF on the development of bovine embryos in culture with the effects described for bLIF. Oocytes were matured and fertilized in vitro and cultured in modified synthetic oviduct fluid with BSA. On Day 6 post-insemination, morulae were cultured for 48h in the presence of: (1) mLIF, 100ngml(-1); (2) hLIF, 100ngml(-1); or (3) no LIF. Reduced blastocyst rates were observed on Day 8 for hLIF at the middle and expanded stages, while mLIF had no effect. In contrast, Day 8 blastocysts showed decreased cell counts both in terms of inner cell mass (ICM) and ICM/total cell proportions in the presence of mLIF, while hLIF had no effect. No changes were seen in trophectoderm (TE) and total cell counts. The increased hatching rates and TE cell counts previously described for bLIF, together with the disparate effects exhibited by hLIF and mLIF during blastocyst formation indicate these compounds are inappropriate to replace bLIF. We recommend that heterospecific LIF should not be used to supplement the culture medium for bovine embryo or embryonic stem cells.
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Bovinos/embriologia , Desenvolvimento Embrionário/fisiologia , Fertilização in vitro/veterinária , Fator Inibidor de Leucemia/farmacologia , Animais , Contagem de Células/veterinária , Feminino , Humanos , Modelos Lineares , Masculino , CamundongosRESUMO
Gene therapy is a very attractive strategy in experimental cancer therapy. Ideally, the approach aims to deliver therapeutic genes selectively to cancer cells. However, progress in the improvement of gene therapy formulations has been hampered by difficulties in measuring transgene delivery and in quantifying transgene expression in vivo. In clinical trials, endpoints rely almost exclusively on the analysis of biopsies, which provide limited information. Non-invasive monitoring of gene delivery and expression is a very attractive approach as it can be repeated over time in the same patient to provide spatiotemporal information on gene expression on a whole body scale. Thus, imaging methods can uniquely provide researchers and clinicians the ability to directly and serially assess morphological, functional and metabolic changes consequent to molecular and cellular based therapies. This review highlights the various methods currently being developed in preclinical models.
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Diagnóstico por Imagem/métodos , Neoplasias/diagnóstico , Animais , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Humanos , Neoplasias/genética , Neoplasias/terapiaRESUMO
INTRODUCTION: Interpretation of the performance on cognitive tests for neuropsychological assessment in multiple sclerosis (MS) differs according to the educational level of the examinee. AIMS: To provide normative data for the Brief Neuropsychological Battery (BNB) for MS stratified by age and education, as well as to demonstrate the utility of the battery for discriminating between healthy controls and patients with MS. SUBJECTS AND METHODS: Data from 701 healthy volunteers from the original normative sample were stratified by age and education using regression analyses of standard scores. Performance of the healthy control group was compared to a group of 112 patients with MS. RESULTS: Significant differences on the BNB were found between groups, mainly in tasks of information processing speed, working memory and verbal memory. Age and sex variables did not have a significant effect on the results. CONCLUSIONS: Our data indicate that the BNB for MS is sensitive for identifying cognitive impairments in MS, specifically in tasks measuring working memory.
TITLE: Bateria neuropsicologica breve en la esclerosis multiple. Baremacion normativa estratificada por edad y nivel educativo.Introduccion. La interpretacion del rendimiento en los tests cognitivos utilizados en la evaluacion neuropsicologica de pacientes con esclerosis multiple difiere en funcion del nivel educativo del evaluado. Objetivos. Aportar datos normativos de la bateria neuropsicologica breve (BNB) en la esclerosis multiple, estratificados por edad y nivel educativo, y demostrar la utilidad de la bateria para discriminar entre sujetos sanos y pacientes con esclerosis multiple. Sujetos y metodos. Se utilizaron los datos de 701 controles sanos de la muestra de baremacion original de la BNB en la esclerosis multiple, y se estratificaron por edad y nivel educativo mediante analisis de regresion de puntuaciones escalares. Se comparo el rendimiento del grupo control con un grupo de 112 pacientes con esclerosis multiple. Resultados. Se hallaron diferencias significativas entre los grupos en las variables de la BNB, en especial en tareas de velocidad de procesamiento, memoria de trabajo y memoria verbal. La edad y el sexo no mostraron efectos relevantes. Conclusiones. Los datos indican que la BNB en la esclerosis multiple es una herramienta sensible para identificar alteraciones cognitivas en la esclerosis multiple, con especial enfasis en las tareas de memoria de trabajo.
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Esclerose Múltipla/psicologia , Testes Neuropsicológicos , Adolescente , Adulto , Fatores Etários , Atenção , Percepção Auditiva , Estudos de Casos e Controles , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Avaliação da Deficiência , Escolaridade , Feminino , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Distúrbios da Fala/diagnóstico , Distúrbios da Fala/etiologia , Distúrbios da Fala/psicologia , Aprendizagem Verbal , Adulto JovemRESUMO
Cancer is a multigenic disorder involving mutations of both tumor suppressor genes and oncogenes. A large body of preclinical data, however, has suggested that cancer growth can be arrested or reversed by treatment with gene transfer vectors that carry a single growth inhibitory or pro-apoptotic gene or a gene that can recruit immune responses against the tumor. Many of these gene transfer vectors are modified viruses. The ability for the delivery of therapeutic genes, made them desirable for engineering virus vector systems. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Because these vector systems have unique advantages and limitations, each has applications for which it is best suited. Retroviral vectors can permanently integrate into the genome of the infected cell, but require mitotic cell division for transduction. Adenoviral vectors can efficiently deliver genes to a wide variety of dividing and nondividing cell types, but immune elimination of infected cells often limits gene expression in vivo. Herpes simplex virus can deliver large amounts of exogenous DNA; however, cytotoxicity and maintenance of transgene expression remain as obstacles. AAV also infects many non-dividing and dividing cell types, but has a limited DNA capacity. This review discusses current and emerging virusbased genetic engineering strategies for the delivery of therapeutic molecules or several approaches for cancer treatment.
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Antineoplásicos/uso terapêutico , Terapia Genética/métodos , Neoplasias/terapia , Terapia Viral Oncolítica/métodos , Técnicas de Transferência de Genes , Vetores Genéticos , Neoplasias/virologiaRESUMO
A peripherally inserted central catheter (PICC) was inserted into a 44-year-old man to provide parenteral nutrition in a protein-calorie malnutrition secondary to a benign pyloric stenosis. On the fifth day while monitoring the catheter, the patient presented with a massive whitish pleural effusion after undergoing gastric endoscopy in order to treat pyloric stenosis. Chylothorax was initially suspected, and the patient was admitted to a recovery unit. Indocyanine green was administered through the PICC, obtaining a greenish discoloration in the pleural effusion 30 min later. This led to the diagnosis of a pleural effusion caused by a vessel perforation due to the PICC, leading to parenteral nutrition extravasation. Thoraco-abdominal computed tomography was performed, which confirmed an innominate vein perforation due to the PICC. PICC insertion may be associated with severe complications, such as central vessel perforation, and therefore the correct position of a central catheter should be always checked. Intravenous computed tomography contrast is the gold standard for central vascular perforation diagnosis. However if a pleural effusion occurs in this context, it is possible to use a dye, which administered intravenously can lead us to the correct diagnosis in situ. Indocyanine green was used for this purpose in this case.
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Derrame Pleural/etiologia , Adulto , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Humanos , Verde de Indocianina , Masculino , Nutrição Parenteral Total/efeitos adversosRESUMO
Chediak-Higashi syndrome (CHS) is an autosomal recessive disease characterized by the presence of abnormally large cytoplasmic organelles in all body granule producing cells. The molecular mechanism for this disease is still unknown. Functional disorders in membrane-related processes have been reported. Erythrocyte membranes from four CHS patients and 15 relatives including obligatory heterozygous were studied to examine potential alterations in the lipid and fatty acid profile of erythrocyte membranes associated with this syndrome. Plasma concentrations of cholesterol, triglycerides, phospholipids, and apolipoproteins AI and B100, and the lipid components of very low-, intermediate-, low- and high-density lipoproteins were also determined. CHS erythrocyte membranes were found to be enriched with lipids in relation to protein and to show: (1) an increase in cholesterol and choline-containing phospholipids (sphingomyelin and phosphatidylcholine) that predominate in the outer monolayer, which is higher than the increase in phosphatidylserine and phosphatidylethanolamine, that are chiefly limited to the inner monolayer in normal red blood cells; (2) a relative palmitic acid and saturated fatty acid increase and arachidonic acid and unsaturated fatty acid decrease, this resulting in a lower unsaturation index than controls. Changes in CHS erythrocyte membrane lipids seem to be unrelated to serum lipid disorders as plasma lipid and apolipoprotein concentrations were apparently in the normal range, with the exception of a modest hypertriglyceridemia in patients and relatives and a decreased concentration of HDL cholesterol in patients. These findings indicate that CHS erythrocyte membranes contain an abnormal lipid matrix with which membrane proteins are defectively associated. The anomalous CHS membrane composition can be explained on the postulated effects of the CHS1/Lyst gene.
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Síndrome de Chediak-Higashi/metabolismo , Membrana Eritrocítica/metabolismo , Ácidos Graxos/análise , Lipídeos de Membrana/sangue , Adolescente , Adulto , Síndrome de Chediak-Higashi/sangue , Criança , Pré-Escolar , Membrana Eritrocítica/química , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Lipídeos de Membrana/química , Proteínas de Membrana/sangue , Fosfolipídeos/sangue , Fosfolipídeos/químicaRESUMO
Endemic Chediak-Higashi Syndrome occurs in a restricted geographic area (Pregonero, State of Táchira, Venezuela). Neutrophils from these patients were unable to digest Candida albicans in vitro, but showed normal or increased metabolic activities. This finding supports the view that the endemic syndrome is bona fide Chediak-Higashi Syndrome.