No description available.

Thesis (MMed)--Stellenbosch University, 2014 / ENGLISH ABSTRACT: Background With recent literature indicating certain clavicle shaft fracture types are best treated surgically; there is renewed interest in the anatomy of the clavicle. lntramedullary fixation of clavicle shaft fractures requires an adequate medullary canal to accommodate the fixation device used. This computer tomography anatomical study of the clavicle and its medullary canal describes its general anatomy and determines the suitability of its medullary canal to intramedullary fixation. Description of methods Four hundred and eighteen clavicles in 209 patients were examined using computer tomography imaging. The length and curvatures as well as the height and width of the clavicle and its canal at various pre-determined points were measured. ln addition the start and end of the medullary canal from the sternal and acromial ends of the clavicle were determined. The data was grouped according to age, gender and lateralization. Summary of results The average length of the clavicle was 151.15 mm with the average stemal and acromial curvature being 146 and 133 respectively. The medullary canal starts on average 6.59 mm from the sternal end and ends 19.56 mm from the acromial end with the average height and width of the canal at the middle third being 5.61 mm and 6.63 mm respectively. Conclusion The medullary canal of the clavicle is large enough to accommodate commonly used intramedullary devices in the nraprity of cases. The medullary canal extends far enough medially and laterally for an intramedullary device to adequatet'y bridge most middte third clavicle fractures. An alternative surgical option should be avalable in theatre when treating females as the medullary canal is too small to pass an intranedullary device past the fracture site on rare occasions.

Des altérations intra-osseuses liées à l’adiposité médullaire et à ses répercussions sur l’inflammation peuvent jouer un rôle important dans la physiopathologie de certaines maladies de la moelle osseuse (MO). Ces altérations locales, actuellement mal connues, correspondent à une modification de la répartition des différents constituants du tissu osseux et impliquent des interactions entre ostéogenèse et adipogenèse. Des études récentes ont démontré que la MO jaune constitue un tissu adipeux spécifique, différent des tissus adipeux blanc ou brun. Ces études suggèrent qu’elle pourrait avoir un rôle dans la pathogénie d’un grand nombre de pathologies de la moelle osseuse, notamment à la hanche.La spectroscopie par IRM (IRMS) présente l’intérêt d’évaluer, de façon quantitative et non invasive, le contenu graisseux au sein de la MO jaune, en complément des informations diagnostiques obtenues avec séquences IRM conventionnelles. Grâce aux IRM 3T, une amélioration de la qualité spectrale avec des temps d’acquisition adaptés à la pratique clinique peut être espérée. Or, cette technique n’a quasiment pas été évaluée à la hanche et aucune évaluation de la reproductibilité ni aucunes valeurs normales n’ont été étudiées, validées et publiées à ce jour.Le but de ce travail de recherche a donc été d’établir le rôle de la spectroscopie 1H par IRM 3T dans l’évaluation quantitative de la moelle osseuse de la hanche.Notre travail s’est articulé autour de trois axes, donnant lieu au développement des 3 parties de cette thèse.La première étude a porté sur la mise au point de la technique spectroscopique à la hanche et sur l’évaluation de la reproductibilité de cette technique avec une machine IRM 3 Tesla, puisque cela n’avait pas été étudié.J’ai démontré que la spectroscopie 1H MR à 3 Tesla est une technique fiable, permettant l’obtention de valeurs de contenu graisseux hautement reproductibles au sein de la moelle osseuse de la hanche et qu’aucune différence statistiquement significative du contenu graisseux n’existait entre les deux hanches. Ce travail a été accepté pour publication.Sur cette base, nous avons établi, au cours de la 2ème étude, des valeurs de normalité du contenu graisseux du fémur proximal chez des sujets sains en tenant en compte de l’âge et du sexe de l’individu, étape indispensable pour disposer de données de référence lors de l’évaluation des conditions pathologiques affectant la moelle osseuse à la hanche. Ce travail est actuellement soumis à publication.La 3ème étude, en cours, porte sur la recherche et l’identification potentielle de spectres anormaux de la moelle osseuse de la hanche chez des patients présentant une ONTF ou souffrant d’anorexie mentale. A l’heure actuelle, le recrutement de patients porteurs d’une ONTF est presque terminé et nous disposons de quelques résultats préliminaires. Quant au recrutement des patients atteints d’anorexie mentale, il est actuellement en cours. / Some bone alterations seem to be linked to medullary adiposity that could play a major role in the physiopathology of several disorders involving bone marrow. Although the mechanisms intervening between osteogenesis and adipogenesis are not completely understood, they could be responsible for modifications of bone marrow composition. Some recent studies have demonstrated that yellow bone marrow represents a specific fat tissue, different from white or brown adipose tissues.Moreover these studies suggested that yellow bone marrow could have a significant role in the pathogenesis of several bone marrow diseases, especially involving the hip.MRI spectroscopy permits a quantitative non-invasive evaluation of the fat content of bone marrow, completing the diagnostic findings obtained with traditional IRM examination. 3 T MRI enables an improvement of spectra quality with relatively short acquisition time and it is adequate to clinical practice.The value of this technique has been poorly evaluated at the hip and no reproducibility studies or no normal values have been determined or published so far.The goal of the present research was to assess the role of 1H MR spectroscopy in the quantitative evaluation of hip bone marrow.This aim of this research project was threefold.The first axis of research was oriented to set the spectroscopic technique and to evaluate its reproducibility in the evaluation of hip bone marrow using a 3 T magnet. To the best of our knowledge this had not been assessed earlier. We demonstrated that 1H 3 T MRI spectroscopy is a reliable technique that permits to obtain highly reproducible fat content values of the hip bone marrow. Moreover we proved that no statistical significant difference existed when comparing left and right fat content values in the same individual. The results of this work have been accepted for publication.On this basis we obtained, within the second axis of this research project, normal hip fat content values in healthy subjects taking into account the age and the gender. This study enables to dispose of normal reference values in order to assess pathological conditions of hip bone marrow.The third axis of this project is on going. It concerns the research and the identification of possible abnormal spectra of hip bone marrow in patients affected from femoral head osteonecrosis or anorexia nervosa. At this time point, the recruitment of patients with osteonecrosis is over and we dispose of some preliminary results. The recruitment of patients affected from anorexia nervosa is currently in course.

Dominant-activating mutations in the RET (rear-ranged during transfection) proto-oncogene, which encodes a receptor tyrosine kinase, is often associated with the development of medullary thyroid carcinoma (MTC). The proximal promoter region of the RET gene consists of a guanine-rich sequence containing five runs of three consecutive guanine residues that serve as the binding site for transcriptional factors. As we have recently shown, this stretch of nucleotides in the promoter region is highly dynamic in nature and tend to form non-B DNA secondary structures called G-quadruplexes, which suppress the transcription of the RET gene. In the present study, ellipticine and its derivatives were identified as excellent RET G-quadruplex stabilizing agents. Circular dichroism (CD) spectroscopic studies revealed that the incorporation of a piperidine ring in an ellipticine derivative, NSC311153 improves its binding with the G-quadruplex structure and the stability induced by this compound is more potent than ellipticine. Furthermore, this compound also interfered with the transcriptional mechanism of the RET gene in an MTC derived cell line, TT cells and significantly decreased the endogenous RET protein expression. We demonstrated the specificity of NSC311153 by using papillary thyroid carcinoma (PTC) cells, the TPC1 cell line which lacks the G-quadruplex forming sequence in the promoter region due to chromosomal rearrangement. The RET downregulation selectively suppresses cell proliferation by inhibiting the intracellular Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways in the TT cells. In the present study, we also showed that the systemic administration of a water soluble NSC311153 analog in a mouse MTC xenograft model inhibited the tumor growth through RET downregulation.

Resumo: O carcinoma medular de tireóide familiar (CMTF) é uma doença autossômica dominante relacionada a mutações do proto-oncogene RET, que ocorre principalmente nas regiões cisteínas da proteína RET dependentes dos códons 10 e 11. Responde por 5 a 15% dos casos de CMT hereditários. Para caracterizar o CMT de natureza familiar, este deve estar presente em pelo menos 4 indivíduos de uma mesma família. O presente trabalho objetivou o estudo clínico-genético de uma família portadora de carcinoma medular de tireóide. Esta família consiste de 25 indivíduos (13 homens e 2 mulheres) distribuídos em três gerações. Destes, seis apresentam a doença ativa: um homem da 1ª geração e dois homens e três mulheres da 2ª geração. Nenhum membro da 3ª geração desenvolveu a doença até agora. Foram coletadas amostras de sangue periférico de 19 desses indivíduos. Nestas amostras foram realizadas amplificações dos segmentos gênicos de interesse pela técnica da reação em cadeia da polimerase (PCR) e os respectivos seqüenciamentos. Até o momento, detectou-se em dois indivíduos, mutação no códon 10 (cys611tyr). Esta mutação tem uma incidência baixa (1-3%) nos casos de CMTF, mas, no entanto, implica em alto risco de agressividade do tumor. Além disso, detectou-se a presença de 3 polimorfismos (G691S, L769L, S904S), nos éxons 11, 13 e 15. Enquanto que a mutação cys611tyr está relacionada ao desenvolvimento do CMTF, sua relação com os polimorfismos encontrados e o papel desta relação com esses tumores não está esclarecida. A realização do rastreamento genético das mutações no RET deve ser considerada pela sua praticidade, custo-benefício e sensibilidade e especificidade do método. Além disso, a determinação de mutações nos familiares com CMT implicará em indicação cirúrgica preventiva e aconselhamento genético familiar. / Abstract: Familial medullary thyroid carcinoma (FMTC) is an autosomic dominant disorder related to mutations in the RET proto-oncogene. These mutation occur mostly in the extracellular rich cistein domains of the RET protein, related to the codons 10 and 11. The FMTC represents 5-15% of hereditary medullary thyroid carcinoma (MTC). To characterize MTC of familial origin, at least four members of a family must be affected. The present study focused upon clinical-genetics characteristics of a 25-member family (13 men and 12 women) distributed through three generations. Six of them had MTC: one first generation man, two men and three women from the second generation. Up until now, no member from the third generation has developed the disease. We studied 19 of these individuals for mutations in the RET protooncogene. A cys611tyr mutation was found in two of the kindreds. This mutation has a low incidence (1-3%) in FMTC, but implies in high aggressiveness risk. Moreover, we found the polymorphisms G691S, L769L, S904S in the exons 11, 13 and 15, respectively. While cys611tyr mutation is responsible for cases of FMTC, its relationship to these polymorphisms and the consequences of this interrelation to tumor development is still unknown. The screening for RET proto-oncogene mutations in relatives of MTC patients must be considered for its practicability, low cost, high specificity and sensibility. Besides, the determination of mutations in FMTC patients' kindred will conduct them to prophylactic surgery and familial counseling. / Orientador: Célia Regina Nogueira / Coorientador: Denise Perone / Banca: Glaúcia Mozeto / Banca: Laura Ward / Doutor

Various opioids were used to investigate the role they might play in the cardiovascular responses to fatiguing isometric contractions. Changes in blood pressure were measured in cats anaesthetised with α-chloralose. Fatiguing isometric contractions of the hind limb muscles (ergoreceptor activation) were generated using a microprocessor controlled stimulator (50 Hz, 0.2 ms, 200-800 mV). Baroreceptor inactivation was elicited by carotid artery occlusion. Muscle contraction caused an increase in mean arterial pressure of 51 (SEM 12) mm Hg and carotid occlusion an increase of 56(9) mm Hg above resting levels in control conditions. Injection of dynorphin (0.5-5.0 μg·5 μl-1) into the cerebral aqueduct just rostra1 to the 4th ventricle eliminated the pressor response to muscular contraction (mean arterial pressure at rest, 80-118 mm Hg: on fatigue, 72-129 mm Hg) but did not affect the pressor response to carotid occlusion in the same cats. Similarly, injections of met-enkephalin (1-100 μg·5 μl-1) or β-endorphin (10-100 μg·5 μl-1) eliminated the ergoreceptor induced changes in mean arterial pressure during isometric contractions but had no effect on the changes caused by carotid occlusion. Pressor responses to nerve crush were not eliminated. These results support the suggestion that a catecholaminergic-opioidergic pathway in part mediates the cardiovascular responses to ergoreceptor afferent but probably not baroreceptor afferent input.

No description available.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Orientador: Gláucia Maria Ferreira da Silva Mazeto / Resumo: Contexto: O carcinoma medular de tireoide (CMT) é um tumor raro, cujo diagnóstico precoce é extremamente relevante uma vez que sua evolução pode ser bastante agressiva. A dosagem sérica de calcitonina pode indicar o diagnóstico do CMT e é utilizada como marcador da presença de doença durante o seguimento dos pacientes. No Hospital das Clínicas da Faculdade de Medicina de Botucatu (HC-FMB), a dosagem do hormônio passou a ser realizada em 2008, sendo sua solicitação de livre acesso. Objetivos: Avaliar as solicitações de dosagem de calcitonina sérica no HC-FMB, independentemente do diagnóstico ou procedimento terapêutico realizados. Pacientes e Métodos: Foram avaliadas, retrospectivamente, todas as dosagens de calcitonina realizadas no Laboratório de Análises Clínicas do HC-FMB, no período de setembro de 2008 a junho de 2017. Foram então comparados os casos com calcitonina detectável ou não, aqueles com e sem CMT e os casos com solicitação de dosagem considerada adequada ou inadequada/não informada. Foi ainda quantificado o custo com as dosagens adequadas e inadequadas/não informadas. Resultados: Foram realizadas 1453 dosagens de calcitonina, em 915 pacientes, com concentrações detectáveis que variaram de 2,00 pg/mL a 527,00 pg/mL (mediana= 4,1 pg/mL). A mais frequente justificativa da coleta foi nódulo tireoidiano (73,9%). Dezenove pacientes (2,1%) apresentaram diagnóstico final de CMT. A maior parte dos casos apresentou calcitonina indetectável (82,7%). A maioria dos pacientes... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Context: Medullary thyroid cancer (MTC) is a rare tumor, which early diagnosis is extremely relevant since its evolution can be quite aggressive. Serum calcitonin dosage may indicate the diagnosis of MTC and is used as a marker of the disease presence during the patients’ follow-up. At the Clinics Hospital of the School of Medicine of Botucatu (HC-FMB), the dosage of the hormone was first carried out in 2008, being its request of free access. Objectives: To evaluate the serum calcitonin dosage requirements in the HC-FMB, regardless of the diagnostic or therapeutic procedure carried out. Patients and Methods: All calcitonin dosages carried out at the Clinical Analysis Laboratory of HC-FMB from September 2008 to June 2017 were retrospectively evaluated. The cases with or without detectable calcitonin, as well as the cases with or without MTC, and the cases with adequate or inadequate/not informed dosage request were then compared. Costs with appropriate and inadequate/not informed dosages were also quantified. Results: 1453 calcitonin dosages have been carried out in 915 patients with detectable concentrations ranging from 2.00 pg/mL to 527.00 pg/mL (median = 4.1 pg/mL). The most frequent justification for the collection was thyroid nodule (73.9%). Nineteen patients (2.1%) were eventually diagnosed with MTC. The majority of cases had undetectable calcitonin (82.7%). The majority of MTC patients (73.7%) had detectable calcitonin, and 42.1% of those patients had concentrations ab... (Complete abstract click electronic access below) / Mestre

Através do ultra-som, um método de diagnóstico seguro e preciso, podemos estabelecer a relação córtico-medular (RCM) renal avaliando o volume da cortical e da medular acrescentando uma avaliação quantitativa ao método usado nas interpretações ultra-sonográficas, que ainda são de caráter qualitativa (subjetiva) e dependem da habilidade, do equipamento e da experiência do médico veterinário que estará fazendo o exame. Utilizamos 30 animais de diferentes raças, com idades entre 1 e 9 anos, machos e fêmeas, com pesos na faixa de 9 até 40 Kg, provenientes de clínicas veterinárias particulares. Todos passaram por exames clínico e físico, mostrando-se sadios e sem histórico de doença ou problemas renais, o que foi confirmado através de exames laboratoriais. Após as aferições por ultra-som as medidas foram colocadas em fórmulas, que deram os volumes de córtex e medula, seguindo então para uma relação mais precisa córtex/medula. Os resultados mostraram que os valores de RCM vão de 2,26 a 3,33 independentemente do volume renal, sexo, peso e idade, sendo estas variantes de baixa significância com a relação córtico-medular / Through the ultrasound, a insurance and exact diagnostic, we can establish renal corticomedullary correlation (RCM) evaluating the volume of the cortical and medullary adding a quantitative evaluation to the used method in the interpretations ultrasonographics, that still are of qualitative character (subjective) and depend on the ability, the equipment and the experience of the medical veterinarian who will be making the examination. We use 30 animals of different races, with ages between 1 and 9 years, males and females, with weights in the band of 9 up to 40 kg, proceeding from clinical particular veterinarians. All had passed for examinations clinical and physical, revealing healthy and without description of illness or renais problems, what it was confirmed through laboratoriais examinations. After the gaugings for ultrasound the measures had been placed in formulas, which had given to the volumes of cortex and medullary, following then for a more necessary corticomedullary correlation. The results had shown that the values of RCM independently go of 2,26 the 3,33 of the renal volume, sex, weight and age, being these variants of low significance with the corticomedullary correlation.