O desenvolvimento de um método eficiente de avaliação prognóstica precoce seria de grande utilidade na seleção de lactentes com plexopatia braquial obstétrica para cirurgias de reconstrução do plexo braquial. Realizamos estudos de condução motora em 54 pacientes entre 10 e 60 dias de vida. Foram comparadas lado a lado as amplitudes dos potenciais de ação musculares compostos dos nervos axilar (músculo deltóde), musculocutâneo (músculo bíceps), radial proximal (músculo tríceps), radial distal (músculo extensor comum dos dedos), mediano (eminência tenar) e ulnar (eminência hipotenar). A relação entre a amplitude do potencial motor do lado lesado sobre o lado são foi chamada de Índice de Viabilidade Axonial (IVA), sendo este calculado tanto a partir da amplitude negativa como da amplitude pico-a-pico. Os pacientes foram seguidos clinicamente e classificados em três grupos: Grupo A, com recuperação total até os seis meses de vida; Grupo B, recuperação satisfatória até os doze meses de vida, e Grupo C, recuperação insatisfatória até os doze meses de vida. Analisamos a curva ROC (Receive Operator Characteristic Curve) de cada IVA para definir o melhor ponto de corte para detecção dos pacientes do Grupo C (mau prognóstico). Para o nervo axilar, o ponto de corte ideal foi IVA menor que 10%, com sensibilidade de 88,2% e especificidade de 89,2% ou 91,9%. Para o nervo musculocutâneo, o ponto de corte foi a ausência de potencial de ação motor, com sensibilidade de 88,2% e especificidade de 73,0%. Para o nervo radial proximal, o ponto de corte foi IVA menor que 20%, com sensibilidade de 82,4% ou 94,1% e especificidade de 97,3% ou 100%. Para o nervo radial distal, o ponto de corte foi IVA menor que 50%, com sensibilidade de 76,5% ou 82,4% e especificidade de 97,3%. Para o nervo ulnar, o ponto de corte foi IVA menor que 50%, com sensibilidade de 58,8% e especificidade de 97,3% ou 100%. O IVA do nervo mediano teve um desempenho ruim e seu uso não pode ser recomendado. Os IVAs dos nervos radial proximal, radial distal e ulnar apresentaram maior especificidade do que o critério clínico mais utilizado para a avaliação prognóstica, ou seja, ausência de função bicipital aos três meses de vida. A sensibilidade dos IVAs dos nervos axilar, musculocutâneo, radial proximal e radial distal foram equivalentes à do critério clínico. A utilização do estudo de condução motora entre 10 e 60 dias de vida forneceu uma avaliação prognóstica mais precoce e mais específica do que o critério clínico, podendo ser utilizada para indicação cirúrgica destes pacientes. / Early prognostic assessment of obstetric brachial plexopathies would be a major step for rational selection of infants for brachial plexus surgery. We performed nerve conduction studies in 54 patients from 10 to 60 days of life. We compared sideto-side the compound muscle action potentials amplitudes from the axillary (deltoid muscle), musculocutaneous (biceps), proximal radial (triceps), distal radial (extensor digitorum communis), median (thenar eminence) and ulnar nerves (hypothenar eminence). The ratio between the amplitude of the affected limb and that of the healthy side was called Viability Axonal Index (VAI), which was calculated using both the negative and the peak-to-peak amplitudes. The patients were followed-up and classified in three groups: Group A, with full recovery at six months of age; Group B, with satisfactory recovery at twelve months of age, and Group C, with poor recovery at twelve months of age. We analyzed the ROC (Receive Operator Characteristic) curve of each VAI to define the best cut-off point for detection of Group C patients (bad prognosis). The best cut-off point for the axillary nerve was a VAI of less than 10%, whith sensibility of 88.2% and specificity of 89.2% or 91.9%. For the musculocutaneous nerve, the cut-off point was an absent motor action potential, with sensibility of 88.2% and specificity of 73.0%. For the proximal radial nerve, the cut-off point was a VAI of less than 20%, with sensibility of 82.4% or 94.1% and specificity of 97.3% or 100%. For the distal radial nerve, the cut-off point was a VAI of less than 50%, with sensibility of 76.5% or 82.4% and specificity of 97.3%. For the ulnar nerve, the cut-off point was a VAI of less than 50%, which sensibility of 58.8% and specificity of 97.3% or 100%. The VAI from the median nerve had a poor performance and its use could not be recommended. The VAIs from proximal radial, distal radial and ulnar nerves had better specificities compared to the most used clinical criterion: absence of biceps function at three months of age. The VAIs sensitivities from axillary, musculocutaneous, proximal radial and distal radial nerves were equivalent to the clinical criterion. The use of motor conduction studies between 10 and 60 days of age yielded an earlier and more specific prognostic estimation than the clinical criterion, and could be used for indication of surgery in these patients.

O ácido 2,4 diclorofenoxiacético (2,4-D) é um herbicida amplamente utilizado na agricultura sendo moderadamente tóxico para os seres humanos e demais animais. Apresenta neurotoxicidade, mas seu mecanismo de ação no sistema nervoso não está totalmente esclarecido. Há indícios de que este herbicida atue nos neurônios serotoninérgicos e dopaminérgicos de maneira seletiva, mas não há estudos suficientes para afirmarem sua exata ação sobre o sistema nervoso periférico. Entre os efeitos advindos da intoxicação com 2,4-D estão manifestações gastrointestinais. O presente trabalho teve como objetivo verificar os efeitos da administração do 2,4-D diluído em água nos neurônios mioentéricos do duodeno de ratos. Para tanto, 36 ratos (Rattus norvegicus) foram separados em três grupos (n = 12): controle (C); tratamento com 2,5 &#956;g/Kg de 2,4-D (B) e tratamento com 5 &#956;g/Kg de 2,4-D (A). Após 15 dias de experimento, os animais foram anestesiados, eutanasiados e seus duodenos foram retirados. Os neurônios mioentéricos foram evidenciados por meio de preparados de membrana corados pelo método de Giemsa e pela técnica de evidenciação neuronal pela ação da NADH-diaforase. Estes preparados de membrana foram analisados ao microscópio de luz para contagem dos neurônios e através de programa computadorizado de análise de imagens foi feita a mensuração do perfil do corpo celular (PCC) desses neurônios. A análise quantitativa demonstrou diminuição no número de neurônios do duodeno nos animais que receberam 2,4-D, em ambas as técnicas (p<0,05). Predominaram nos três grupos de animais neurônios de tamanho entre 101 e 300&#956;m2. A incidência de neurônios grandes (entre 301 e 600 µm2) foi significantemente maior (p<0,05) nos animais tratados com 2,4-D. Os resultados sugerem que o 2,4-D afeta o plexo mioentérico, sendo sua ação neurotóxica manifestada pela diminuição no número de neurônios e aumento no número de neurônios grandes. / The 2,4 dichlorophenoxyacetic acid (2,4-D) it is a herbicid thoroughly used in the agriculture and it is poisonous for the human beings and other animals. It presents neurotoxicity but its action mechanism in the nervous system is not totally known. There are evidences that herbicid actuate on selective mode in serotoninergics and dopaminergics neurons, but there isn?t significant studies to prove its discuss action on the peripheric nervous system. Among the effects succeeding of the intoxication with 2,4-D are gastrointestinal manifestations. The present work had as objective verifies the effects of the administration for 15 days of 5 &#956;g and 2,5 &#956;g/Kg of body weight of 2,4-D diluted in water in the duodenum myenteric neurons of the rats. In order to do so, 15 rats (Rattus norvegicus) were divided into three groups (n = 12): controls (C); treatment with 2,5&#956;g/Kg of 2,4-D (B); and treatment with 5&#956;g/Kg of 2,4-D (A). 15 days later, the animals were anesthetized, killed without pain and your duodenums were removed. The myenteric neurons were stained employing the Giemsa and the NADH-diaforase methods by means of whole mounts preparations. These whole mounts preparations were analyzed in light microscope to count the neurons and through image analysis software to measured the cellular body profile (CBP) of these neurons. The quantitative analysis evidenced reduction in the number of duodenum neurons in animals which received 2,4-D, in both techniques (p<0,05). Predominated in three groups neurons with size between 101 and 300 &#956;m2. Incidence of big neurons (between 301 e 600 &#956;m2) was significantly higher (p<0,05) in the treated with 2,4-D. The results suggest that the 2,4-D affect the myenteric plexus, and its action is expressed by reduction in neurons number and increase in incidence of big neurons.

A Anatomia comparativa de mamíferos vem sendo tema de pesquisas, nas áreas biomédica e biológica com o objetivo de se buscar conhecimentos que possam auxiliar na busca sobre o entendimento do binômio unidade-variedade, dentre os símios tem sido particularmente enfocados o Babuíno e o Rhesus que, entretanto, não são próprios do Novo Mundo. O Cebus apella, animal das matas do continente Sul-americano, distribuindo-se geograficamente por quase todo o Brasil, apresenta satisfatória adaptação à vida em cativeiro condição em que, inclusive, se reproduz com facilidade. Assim, é de nosso interesse focalizar, o Cebus apella, analisando a origem, a composição e os nervos resultantes de seu plexo braquial. O objetivo imediato deste trabalho é, dar seqüência ao conhecimento de sua Anatomia, visando também o fornecimento de subsídios para interpretações anatómo-funcionais do Cebus apella, comparativamente a outros animais. O objetivo a médio e a longo prazos é o estabelecimento do padrão anatômico deste animal, culminando com a elaboração de um Atlas - texto sobre a Anatomia do macaco Cebus apella. Utilizamos 20 animais, sendo 10 machos e 10 fêmeas, adultos, pertencentes ao acervo de pesquisas da Universidade Federal de Uberlândia. A preparação das peças anatômicas foi feita segundo a metodologia usual em estudos anatômicos. Os principais nervos oriundos do plexo braquial são: supraescapular, subescapular, musculocutâneo, radial, mediano, ulnar, axilar, toracodorsal, peitoral maior e peitoral menor. Em 57% dos espécimes dissecados o plexo braquial do Cebus está constituído por raízes de C5 a T1, em 21,4% de C5 a T2, em 14,3% de C4 a T1 e em 7,3% de C4 a T2. O plano dorsal do plexo braquial contribui para a formação dos nervos: frênico, peitoral maior e peitoral menor. O plano médio origina os nervos musculocutâneo, mediano, ulnar e cutâneo medial do antebraço, enquanto o plano ventral dá origem aos nervos supraescapular, subescapular, axilar, radial e torácico longo. Discute-se a ocorrência de pré e de pós-fixação do plexo, bem como a de seu deslocamento cranial e caudal. Em conclusão o plexo braquial do Cebus apella está constituído por raízes de C5 a T1 e é organizado em um plano ventral mais simples, um médio de complexidade intermediária e um dorsal mais complexo. / Comparative Anatomy of mammals has been a relevant theme of researches in the biomedical and biological areas with the objective of looking for more information that can aid for searching on the understanding of the unit-variety complex. Among the simians, Baboon and Rhesus have been particularly focused, although they are not from the New World. The monkey Cebus apella, animal of the forests of the South American continent, being geographically distributed for almost the whole Brazil, presents satisfactory adaptation to the captive life showing a great easiness of reproduction. Thus, we intended to study the monkey Cebus apella, analyzing the origin, the composition and the resulting nerves of its brachial plexus. The immediate objective of this study was to add information to the knowledge of its Anatomy, seeking the supply of subsidies for anatomo-functional interpretations of Cebus apella comparatively to humans and domestic animals. Further, we propose to establish the anatomical pattern of this animal, culminating with the elaboration of an Atlas - text on the Anatomy of the monkey Cebus apella. Twenty adult animals, 10 male and 10 female, belonging to the collection of anatomical pieces of the Anatomy Laboratory of the Federal University of Uberlândia were obtained and prepared through fixation and dissection. The major nerves originating from the brachial plexus were: the suprascapular, the subscapular, the musculo-cutaneous, the radial, the median, the ulnar, the axillary, the thoraco-dorsal, the pectoralis major and the pectoralis minor. In the dissected specimens, the brachial plexus of Cebus apella was constituted by the roots from C5 to T1 (55,00 ± 11,12%), from C5 to T2 (25,00 ± 9,68%), from C4 to T1 (15,00 ± 7,98%) and from C4 to T2 (5,00 ± 4,87%). The ventral plan of the brachial plexus contributed for the formation of the following nerves: the phrenic, the subclavius, the pectoralis major, and the pectoralis minor. The medium plan originated the musculo-cutaneous, the median, the ulnar, and the forearm medial cutaneous nerves, while the dorsal plan originated the suprascapular, the subscapular, the axillary, the radial, thoraco-dorsal and the long thoracic nerves. In addition, the occurrence of pre- and post- fixation of the plexus as well as its cranial and caudal displacement have been discussed. In conclusion, the brachial plexus of Cebus apella constituted by the roots from C5 to T1 is organized in a simpler ventral plan, a medium plan of intermediate complexity and a more complex dorsal plan.

Prognostic factors come in a variety of forms and may be patient, tumour or environmental related. This thesis examines the interaction of prognostic factors for a variety of tumour types. It particularly focuses on single nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) gene. The first section on meningiomas describes the frequency of sex steroid receptors in meningiomas. In this study, absence of progesterone receptors is associated with high tumour grade and male gender. Tumours that are progesterone receptor negative have an odds ratio for recurrence of 5.Choroid plexus carcinomas are aggressive malignant tumours generally occurring in young children. Gross total surgical resection has been shown to be a highly significant factor in tumour recurrence and survival. This study describes a treatment paradigm of neoadjuvant ICE chemotherapy in these children which decreases the vascularity and increase the chance of a complete removal. The operative blood loss with this regimen is reduced to 0.22 blood volumes from 1.11 blood volumes without neoadjuvant chemotherapy. The VEGF gene is highly polymorphic and SNPs of the region have previously been shown to influence VEGF protein expression. This study looks at cohorts of both adult gliomas and a variety of paediatric brain tumours; comparing them to controls. There are several associations described between the development of certain tumours and specific SNP genotypes. In addition to this, certain genotypes and haplotypes have an influence on survival of adult grade 2 astrocytomas and paediatric medulloblastomas and ependymomas. There are consistent themes to the prognostic genotypes throughout both the adult and the paediatric tumours.Prognostic factors come in a variety forms as described in this thesis. It is vital to understand the complex interaction between factors to best utilise them for the benefit of patients.

Estudos de prognóstico clínico consistem na predição do curso de uma doença em pacientes e são utilizados por profissionais da saúde com o intuito de aumentar as chances ou a qualidade de sua recuperação. Sob a perspectiva computacional, a criação de um modelo prognóstico clínico é um problema de classificação, cujo objetivo é identificar a qual classe (dentro de um conjunto de classes predefinidas) uma nova amostra pertence. Este projeto visa a criar modelos prognósticos de lesões traumáticas do plexo braquial, um conjunto de nervos que inervam os membros superiores, utilizando dados de pacientes adultos com esse tipo de lesão. Os dados são provenientes do Instituto de Neurologia Deolindo Couto (INDC) da Universidade Federal do Rio de Janeiro (UFRJ) e contêm dezenas de atributos clínicos coletados por meio de questionários eletrônicos. Com esses modelos prognósticos, deseja-se identificar de maneira automática os possíveis preditores do curso desse tipo de lesão. Árvores de decisão são classificadores frequentemente utilizados para criação de modelos prognósticos, por se tratarem de um modelo transparente, cujo resultado pode ser examinado e interpretado clinicamente. As Florestas Aleatórias, uma técnica que utiliza um conjunto de árvores de decisão para determinar o resultado final da classificação, podem aumentar significativamente a acurácia e a generalização dos modelos gerados, entretanto ainda são pouco utilizadas na criação de modelos prognósticos. Neste projeto, exploramos a utilização de florestas aleatórias nesse contexto, bem como a aplicação de métodos de interpretação de seus modelos gerados, uma vez que a transparência do modelo é um aspecto particularmente importante em domínios clínicos. A estimativa de generalização dos modelos resultantes foi feita por meio de métodos que viabilizam sua utilização sobre um número reduzido de instâncias, uma vez que os dados relativos ao prognóstico são provenientes de 44 pacientes do INDC. Além disso, adaptamos a técnica de florestas aleatórias para incluir a possível existência de valores faltantes, que é uma característica presente nos dados utilizados neste projeto. Foram criados quatro modelos prognósticos - um para cada objetivo de recuperação, sendo eles a ausência de dor e forças satisfatórias avaliadas sobre abdução do ombro, flexão do cotovelo e rotação externa no ombro. As acurácias dos modelos foram estimadas entre 77% e 88%, utilizando o método de validação cruzada leave-one-out. Esses modelos evoluirão com a inclusão de novos dados, provenientes da contínua chegada de novos pacientes em tratamento no INDC, e serão utilizados como parte de um sistema de apoio à decisão clínica, de forma a possibilitar a predição de recuperação de um paciente considerando suas características clínicas. / Studies of prognosis refer to the prediction of the course of a disease in patients and are employed by health professionals in order to improve patients\' recovery chances and quality. Under a computational perspective, the creation of a prognostic model is a classification task that aims to identify to which class (within a predefined set of classes) a new sample belongs. The goal of this project is the creation of prognostic models for traumatic injuries of the brachial plexus, a network of nerves that innervates the upper limbs, using data from adult patients with this kind of injury. The data come from the Neurology Institute Deolindo Couto (INDC) of Rio de Janeiro Federal University (UFRJ) and they are characterized by dozens of clinical features that are collected by means of electronic questionnaires. With the use of these prognostic models we intended to automatically identify possible predictors of the course of brachial plexus injuries. Decision trees are classifiers that are frequently used for the creation of prognostic models since they are a transparent technique that produces results that can be clinically examined and interpreted. Random Forests are a technique that uses a set of decision trees to determine the final classification results and can significantly improve model\'s accuracy and generalization, yet they are still not commonly used for the creation of prognostic models. In this project we explored the use of random forests for that purpose, as well as the use of interpretation methods for the resulting models, since model transparency is an important aspect in clinical domains. Model assessment was achieved by means of methods whose application over a small set of samples is suitable, since the available prognostic data refer to only 44 patients from INDC. Additionally, we adapted the random forests technique to include missing data, that are frequent among the data used in this project. Four prognostic models were created - one for each recovery goal, those being absence of pain and satisfactory strength evaluated over shoulder abduction, elbow flexion and external shoulder rotation. The models\' accuracies were estimated between 77% and 88%, calculated through the leave-one-out cross validation method. These models will evolve with the inclusion of new data from new patients that will arrive at the INDC and they will be used as part of a clinical decision support system, with the purpose of prediction of a patient\'s recovery considering his or her clinical characteristics.

Vitamin A is an essential nutrient; it is not synthesized by mammals and therefore must be obtained through the diet. During times of fasting or dietary vitamin A insufficiency, retinol, the alcohol form of the vitamin is released from the liver, its main storage tissue, for circulation in complex with retinol-binding protein 4 (RBP) to provide an adequate supply to peripheral tissues. Stimulated by Retinoic Acid 6 (STRA6), the transmembrane RBP receptor, mediates retinol uptake across blood-tissue barriers such as the retinal pigment epithelium of the eye, the placenta and the choroid plexus of the brain. Our understanding as to how this protein functions has been greatly enhanced by the high-resolution 3D structure of zebrafish STRA6 in complex with calmodulin (CaM) solved by single-particle cryogenic-electron microscopy. However, the nature of the interaction of STRA6 with retinol remains unclear. Here, I present the high-resolution structures of zebrafish and sheep STRA6 reconstituted in nanodisc lipid bilayers in the presence and absence of retinol. The nanodisc reconstitution system has allowed us to study this protein in a close to physiological environment and examine its interaction with the cell membrane and relationship with its ligand, retinol. We also present the structure of sheep STRA6 in complex with human RBP. The structure of the STRA6-RBP complex confirms predictions in the literature as to the nature of the protein-protein interaction needed for retinol transport. Calcium-bound CaM is bound to STRA6 in the RBP-STRA6 structure, consistent with a regulatory role of this calcium binding protein in STRA6-RBP interaction. The analysis of the three states of STRA6 – pre, post and during interaction with retinol – provide unique insights into the mechanism of STRA6-mediated cellular retinol uptake.

Ultrasound-guided selective C5 nerve root blocks have been described in several case reports as a safe and effective means to anesthetize the distal clavicle while maintaining innervation of the upper extremity and preserving diaphragmatic function. In this study, cadavers were injected with 5 mL of 0.5% methylene blue dye under ultrasound guidance to investigate possible proximal and distal spread of injectate along the brachial plexus, if any. Following the injections, the specimens were dissected and examined to determine the distribution of dye and the structures affected. One injection revealed dye extended proximally into the epidural space, which penetrated the dura mater and was present on the spinal cord and brainstem. Dye was noted distally to the divisions in 3 injections. The anterior scalene muscle and phrenic nerve were stained in all 4 injections. It appears unlikely that local anesthetic spread is limited to the nerve root following an ultrasound-guided selective C5 nerve root injection. Under certain conditions, intrathecal spread also appears possible, which has major patient safety implications. Additional safety measures, such as injection pressure monitoring, should be incorporated into this block, or approaches that are more distal should be considered for the acute pain management of distal clavicle fractures.

Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50-95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22-75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.

Hip arthroscopy is a minimally invasive alternative to open hip surgery. Despite its minimally invasive nature, there can still be significant reported pain following these procedures. The impact of combined sciatic and lumbar plexus nerve blocks on postoperative pain scores and opioid consumption in patients undergoing hip arthroscopy was investigated. A retrospective analysis of 176 patients revealed that compared with patients with no preoperative peripheral nerve block, significant reductions in pain scores to 24 hours were reported and decreased opioid consumption during the post anesthesia care unit (PACU) stay was recorded; no significant differences in opioid consumption out to 24 hours were discovered. A subgroup analysis comparing two approaches to the sciatic nerve block in patients receiving the additional lumbar plexus nerve block failed to reveal a significant difference for this patient population. We conclude that peripheral nerve blockade can be a useful analgesic modality for patients undergoing hip arthroscopy.

No description available.