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1
Råberg, Knut Sigurd. "Nyhavna arkivbibliotek". Thesis, Norges teknisk-naturvitenskapelige universitet, Fakultet for arkitektur og billedkunst, 2014. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-26690.
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Sætre, Marie, i Line Myrenget. "Å skifte status : trosnøytralt seremonibygg på Nyhavna". Thesis, Norges teknisk-naturvitenskapelige universitet, Fakultet for arkitektur og billedkunst, 2012. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-17648.
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Lorenz, Veronika. "Komplexe Veränderungen in der Genexpression der Ecto-Nukleosid-5-Triphosphat-Diphosphohydrolase bei Hypoxanthin-Phosphoribosyltransferase-Defizienz". kostenfrei, 2008. http://www.opus-bayern.de/uni-regensburg/volltexte/2009/1207/.
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Galloon, Terry. "Biochemical and genetic properties of HPRT Cape Town". Master's thesis, University of Cape Town, 1987. http://hdl.handle.net/11427/26591.
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An unusual partial HPRT deficient mutant, HPRT Cape Town was observed to have a low activity in erythrocyte lysates at high concentrations of the purine substrates, hypoxanthine and guanine. This substrate inhibition was not observed with the substrate PPRP. The low activity was not associated with changes in the Km or Vmax for any of the substrates (Steyn and Harley, 1984). The kinetics of the proband's enzyme was studied in lymphoblast extracts. The characteristic substrate inhibition was observed which showed that this phenomenon was not confined to erythrocytes but was a more generalized phenomenon. This result implies that the decreased HPRT activity observed in the proband is due to substrate inhibition by the purine bases. The HPRT enzyme is coded for by a gene which is located on the X chromosome (Pai et al., 1980). The proband's daughter was therefore studied in order to determine the cause of the mutation. It was not known whether the substrate inhibition was the result of a mutation in the gene coding for the enzyme, a mutation which results in altered post-translational modification or the absence or alteration of factors influencing normal HPRT kinetics. The daughter's transformed lymphoblasts exhibited growth patterns in selective media that resembled those of her father. The daughter's enzyme prepared from lymphoblast extracts exhibited the characteristic substrate inhibition. These results suggest that this cell line results from the selection of a clone or clones which have suppressed the function of the X chromosome carrying the maternal and presumably normal HPRT allele. The daughter's enzyme prepared from erythrocyte lysates exhibited intermediate enzyme activity between that of the proband and a normal control. This result suggests that the daughter is an obligate heterozygote and that the defect is due to a mutation in the HPRT gene itself. The defect was studied at the gene level. No difference was observed in the banding patterns of the proband's DNA and control DNA which were digested with various restriction enzymes and hybridized to ³²p-labelled HPRT cDNA. The size of the HPRT mRNA of the proband was the same as the control. These results imply that there is no major gene alteration; this is expected since the proband only has a partial deficiency of the enzyme. The HPRT cDNA was subcloned into a riboprobe vector, pGEM-3. The T7 promoter was used to transcribe antisense RNA strands which were then hybridized to the proband's RNA and control RNA. No difference was observed in the size of the protected fragment. This result does not exclude the possibility of a point mutation as the cause of the defect in HPRT Cape Town.
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Boyd, Marie. "Evaluation of screening strategies for the detection of molecular pathologies". Thesis, University of Glasgow, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295318.
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Heshka, Timothy William. "Effects of hypoxanthine upon dopamine neurons : an animal model for Lesch-Nyhan disease". Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=59392.
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In Lesch-Nyhan disease, concentrations of hypoxanthine are elevated especially in the brain and cerebrospinal fluid; dopamine and its metabolites are reduced in the caudate and putamen. Hence we investigated the possibility that hypoxanthine has direct effects on dopamine neurons.Hypoxanthine, adenine or allopurinol was delivered unilaterally into the rat brain. Behavioural effects were monitored by apomorphine-induced rotation; ipsilateral turning was time and dose-dependent. Turning was competitively blocked by a non-specific DA antagonist, suggesting that dopamine neurons were altered. In hypoxanthine treated animals, a D1 antagonist specifically blocked rotation; catalepsy occurred after caffeine administration.
After two or three weeks treatment all groups had elevated purine levels in the caudate nuclei, while catecholamine levels were variably altered.
7
Bavaresco, Caren Serra. "Efeito in vitro das substâncias acumuladas na doença de Lesch-Nyhan sobre a atividade da Na+,K+-ATPase em estriado de ratos". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2004. http://hdl.handle.net/10183/5764.
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A doença de Lesch-Nyhan é um erro inato do metabolismo das purinas caracterizado pela deficiência na enzima hipoxantina- guanina fosforibosiltransferase. O bloqueio dessa reação resulta no acúmulo tecidual de hipoxantina, xantina e ácido úrico. A doença caracteriza-se por hiperuricemia, variado grau de retardo mental e motor, espasticidade e auto-mutilação. No sistema nervoso central, a Na+, K+ - ATPase é responsável pela manutenção da homeostase dos íons Na+ e K+, regulando o volume celular, a excitabilidade neuronal, o transporte de neurotransmissores e outras moléculas. Evidências na literatura demonstram que a redução na atividade da Na+, K+ - ATPase está relacionada com diversas doenças neurodegenerativas, tais como isquemia cerebral e doenças de Parkinson e de Alzheimer. No presente estudo, investigamos o efeito in vitro da hipoxantina, xantina e ácido úrico sobre a atividade da Na+, K+- ATPase em membrana plasmática sináptica de estriado de ratos. Estudamos, também, a cinética de inibição causada pela hipoxantina e de interação entre hipoxantina, xantina e ácido úrico. Nossos resultados demonstram que hipoxantina, xantina e ácido úrico inibem significativamente a atividade da Na+, K+- ATPase. O estudo dos mecanismos de inibição da atividade enzimática causados pela hipoxantina demonstrou um efeito inibitório não competitivo com o substrato ATP. Além disso, o estudo de interação cinética entre hipoxantina, xantina e ácido úrico sugere que esses compostos atuem em um mesmo sítio de ligação na enzima. Verificamos, também, o efeito da preincubação de homogeneizado de estriado de ratos na presença de hipoxantina (10 µM) sobre a atividade da Na+, K+- ATPase de membrana plasmática sináptica com a adição ou não de antioxidantes (glutationa e trolox), bem como alguns parâmetros de estresse oxidativo denominados TBARS (medida de lipoperoxidação) e TRAP (capacidade antioxidante tecidual não-enzimática) no intuito de verificar a participação do estresse oxidativo nos mecanismos de inibição enzimática provocados pela hipoxantina. Os resultados monstraram que a hipoxantina inibe significativamente a atividade da Na+, K+- ATPase. Adicionalmente, nossos resultados demonstraram que glutationa, mas não o trolox, na concentração de 1 mM, foi capaz de prevenir a inibição enzimática causada pela hipoxantina. Nossos resultados também mostraram que a hipoxantina, na mesma concentração, aumentou TBARS e diminuiu TRAP que essa substância induz o estresse oxidativo. É possível que a inibição na atividade da Na+, K+- ATPase possa estar envolvida nos mecanismos pelos quais as oxipurinas são neurotóxicas. Acreditamos que nossos resultados possam contribuir, pelo menos em parte, na compreensão da disfunção neurológica encontrada em pacientes portadores da doença de Lesch-Nyhan.
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Ruillier, Valentin. "Utilisation des cellules souches pluripotentes pour le criblage à haut débit de molécules thérapeutiques dans la maladie de Lesch-Nyhan". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLE011/document.
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Les mutations affectant la fonction d'enzymes impliquées dans le cycle des purines sont responsables d'une multitude de syndromes pédiatriques, caractérisés par des atteintes neurologiques et comportementales. A ce jour, aucune stratégie thérapeutique n'a été réellement efficace pour contrôler ces symptômes. La maladie de Lesch-Nyhan (MLN), associée à la perte de fonction de l'enzyme de recyclage HGPRT, constitue un bon modèle d'étude. Mon travail a consisté à utiliser la technologie des cellules souches induites à la pluripotence, reprogrammées à partir de fibroblastes de patients atteints des formes sévères de la MLN, pour identifier des phénotypes neuronaux associés à la perte de fonction de l'HGPRT. Ces marqueurs phénotypiques ont ensuite été utilisés pour identifier, par une approche de criblage à haut débit, de nouvelles molécules chimiques capables de corriger ces défauts. Plus de 3000 molécules ont été testées et 6 composés, tous dérivés de l'adénosine, ont pu être identifiés comme compensant le métabolisme par un mécanisme d'action indépendant de l'HGPRT. De manière intéressante, un des composés, la S-adenosylmethionine (SAM) a par le passé déjà démontré des effets bénéfiques sur les symptômes comportementaux typiques de la MLN dans plusieurs études de cas. Cela démontre que la stratégie abordée ici a permis l'identification de cibles thérapeutiques permettant d'améliorer les symptômes neurospychiatriques de cette pathologie et constitue un modèle réplicable pour différentes pathologies touchant le métabolisme cérébralMutations in genes coding for enzymes involved in purine synthesis or recycling lead to dramatic neurological conditions with poor pharmacological options. Lesch–Nyhan disease (LND) is caused by deficiency of the salvage pathway enzyme HGPRT that compromises recycling of guanine and hypoxanthine into GMP and IMP. LND is characterized by severe neuropsychiatric symptoms that are out of reach of pharmacological treatments. Here we use human cortical neural stem cells and neurons derived from iPSC of children affected by severe forms of LND to identify neural phenotypes associated with HGPRT-deficiency and of interest to develop a target-agnostic based drug screening system. We screened more than 3000 molecules and identified 6 compounds, all possessing an adenosine moiety, that corrected LND related neuronal phenotypes by promoting metabolism compensations in a HGPRT-independent manner. One of these compound, S-adenosylmethionine (SAM), has already been reported as providing amelioration of behavioral symptoms in some LND cases, demonstrating that our screening allowed the identification of pathways that can be relevant therapeutic targets to ease the devastating neuropsychiatric symptoms associated with this pathology. Interestingly, these pathways can be activated in LND patients via simple food supplementation. This experimental paradigm can also be easily adapted to other purine associated neurological disorders affecting normal brain development
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Petitgas, Céline. "Etude des mécanismes pathogéniques de la maladie de Lesch-Nyhan en relation avec le système dopaminergique chez un organisme modèle, Drosophila melanogaster". Thesis, Paris Sciences et Lettres (ComUE), 2019. http://www.theses.fr/2019PSLET049.
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L’adénine phosphoribosyltransférase (APRT) et l’hypoxanthine-guanine phosphoribosyltransférase (HGPRT) sont deux enzymes majeures impliquées dans le recyclage des purines chez les Mammifères, une voie métabolique essentielle permettant la récupération des bases puriques dérivées de l’alimentation ou de la dégradation des nucléotides. La voie de sauvetage des purines est en effet moins coûteuse en énergie que la voie de synthèse de novo et son dysfonctionnement induit diverses pathologies. En particulier, des mutations héréditaires supprimant l’activité de l’HGPRT sont associées à la maladie de Lesch-Nyhan (MLN), une pathologie infantile rare liée à l’X caractérisée par une hyperuricémie et de graves troubles neurocomportementaux tels que dystonie, spasticité et automutilations. Des études ont montré que les patients présentent une diminution significative des taux de dopamine dans les ganglions de la base, sans que l’on comprenne clairement le lien entre la neurotransmission dopaminergique et l’absence d’activité de l’HGPRT. L’objectif de cette thèse a donc été d’étudier la relation entre le sauvetage des purines et le système dopaminergique chez un organisme modèle, la drosophile, afin de mieux comprendre les mécanismes impliqués dans la MLN. La drosophile n’a pas d’homologue de l’HGPRT, ce qui suggère que l’homologue de l’APRT, désignée Aprt, est l’unique enzyme de recyclage des purines chez cet organisme. Nos travaux montrent que des drosophiles mutantes déficientes en Aprt présentent des défauts physiologiques en partie comparables à ceux associés à l’absence d’HGPRT chez l’Homme, notamment un taux élevé d’acide urique ainsi que des altérations des marqueurs dopaminergiques et des troubles neurocomportementaux. A l’inverse, des perturbations génétiques du système dopaminergique induisent une diminution de l’expression et de l’activité de l’Aprt. Nos résultats confirment ainsi la conservation d’un lien physiologique entre le recyclage des purines et le système dopaminergique chez la drosophile, et indiquent de plus que cette régulation fait intervenir la signalisation adénosinergique. Ce nouveau modèle pourrait donc s’avérer utile à terme pour identifier de nouvelles cibles thérapeutiques permettant d’améliorer le traitement de cette maladie dramatiqueAdenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are two major enzymes involved in purine recycling in mammals, an essential metabolic pathway that allows the recovery of free purine bases derived from diet or the degradation of nucleotides. The purine salvage pathway is indeed less energy costly than de novo purine synthesis and its dysfunction induces various pathologies. In particular, inherited mutations suppressing HGPRT enzyme activity are associated with Lesch-Nyhan disease (LND), a rare X-linked metabolic and neurophysiological disorder in children, characterized by hyperuricemia and severe neurobehavioural disturbances such as dystonia, spasticity and compulsive self-injury. Studies have shown that LND patients have markedly reduced dopamine levels specifically in the basal ganglia, but the mechanisms linking the lack of HPRT activity and dopaminergic neurotransmission have not been elucidated to date. In this thesis work, we have been studying the relation between purine metabolism and the dopaminergic system in a model organism, Drosophila, with the aim to find new clues about the mechanisms involved in LND. No HGPRT homologue is present in the Drosophila genome, which suggests that the APRT homologue, named Aprt, is the only purine-recycling enzyme in this organism. Our work shows that Aprt-deficient flies have defects partly comparable to those associated with HGPRT deficiency in humans, notably an increase in uric acid levels, as well as alterations in dopaminergic markers and neurobehavioural defects. Conversely, genetic disruptions of the dopaminergic system decrease the expression and activity level of Aprt. Our results therefore confirm the conservation of a physiological link between purine recycling and the dopaminergic system in Drosophila, and further indicate that this regulation requires adenosinergic signaling. This new model could therefore prove valuable to find new therapeutic targets and possibly improve the cure of this dramatic disease
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Bavaresco, Caren Serra. "Alterações bioquímicas e comportamentais em ratos submetidos à administração intra-estriatal de hipoxantina". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2008. http://hdl.handle.net/10183/13329.
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A síndrome de Lesch Nyhan é um erro inato do metabolismo das purinas, de característica recessiva, ligado ao sexo. Caracteriza-se, bioquimicamente, pela deficiência na atividade da enzima hipoxantina-guanina fosforribosiltransferase (HGPRT), resultando principalmente no acúmulo tecidual de hipoxantina. O quadro clínico manifestado é bastante característico incluindo alterações motoras e cognitivas, retardo mental, espasticidade e automutilação. Considerando que os mecanismos envolvidos nas alterações cerebrais encontradas nessa síndrome ainda são pouco conhecidos, os objetivos do presente estudo foram investigar o efeito da administração intraestriatal de hipoxantina sobre parâmetros bioquímicos cerebrais (atividades da Na+, K+- ATPase e acetilcolinesterase (AChE), parâmetros de estresse oxidativo, hidrólise dos nucleotídeos da adenina) e comportamentais (tarefas do labirinto aquático de Morris, campo aberto e esquiva inibitória) em ratos. Os resultados mostraram que a administração intra-estriatal de hipoxantina reduziu as atividades das enzimas Na+, K+- ATPase e AChE em estriado, hipocampo e no córtex cerebral de ratos. A infusão de hipoxantina aumentou a quimioluminescência,, substâncias reativas ao ácido tiobarbitúrico (TBARS) e atividade da enzima glutationa peroxidase (GPx), e reduziu a capacidade antioxidante tecidual (TRAP) e as atividades das enzimas superóxido dismutase (SOD) e catalase (CAT) em estriado de ratos. As hidrólises dos nucleotídeos da adenina também foram inibidas pela administração de hipoxantina. Os efeitos relatados possivelmente ocorreram através da geração de radicais livres, uma vez que a administração de vitaminas E e C previniu tais efeitos, com exceção do TRAP. Considerando as alterações neuroquímicas induzidas pela administração de hipoxantina observadas em nosso modelo experimental, a próxima etapa desse trabalho foi investigar o papel da administração de hipoxantina sobre a memória/ aprendizagem em ratos na tarefa do labirinto aquático de Morris e esquiva inibitória. A atividade motora dos animais também foi avaliada na tarefa de campo aberto. Os resultados mostraram que a hipoxantina provocou um déficit de V memória/ aprendizado em ambas as tarefas realizadas, contudo não alterou o comportamento motor dos animais. Nossos resultados, em conjunto, mostram que a administração intra-estriatal de hipoxantina provoca uma série de alterações bioquímicas e comportamentais as quais podem, pelo menos em parte, contribuir para as disfunções neurológicas características observadas nesta síndrome. Além disso, se nossas evidências se confirmarem em humanos, a utilização de antioxidantes, tais como as vitaminas E e C, poderão ser utilizados como estratégias terapêuticas a fim de evitar as alterações neurológicas nos pacientes portadores da síndrome de Lesch Nyhan.Lesch Nyhan is an inborn X-linked recessive disease of purine metabolism characterized by deficiency of hypoxanthine-guanine phosphoribosyltranspherase (HGPRT) activity, resulting mainly in tissue accumulation of hypoxanthine. Affected patients present motor and cognitive deficits, spasticity, and self-mutilation behavior. Considering that the mechanisms involved in brain dysfunction found in this syndrome are poorly understood, the general objective of this study was to investigated the effect on intrastriatal hypoxanthine administration on some cerebral biochemical parameters (activities of Na+, K+- ATPase and acetylcholinesterase (AChE), oxidative stress parameters, adenine nucleotide hydrolysis) and behavioral (water-maze, step-down inhibitory avoidance and open field tasks) in rats. Results showed that intrastriatal hypoxanthine administration inhibited Na+, K+- ATPase and AChE in striatum, hippocampus and cerebral cortex of rats. We also verified that hypoxanthine administration increased chemiluminescence, thiobarbituric acid reactive substance (TBARS) and glutathione peroxidase (GPx) activity and reduced total radical-trapping antioxidant parameter (TRAP) and also superoxide dismutase (SOD) and catalase (CAT) activities in striatum of rats. Moreover, adenine nucleotide hydrolysis was also inhibited by hypoxanthine administration. These effects could be probably related to free radical generation since pretreatment with vitamins E and C prevented those effects, excepting for TRAP. Considering the neurochemical alterations provoked by hypoxanthine administration in this experimental model, the next step in this study was to investigate the effect of intrastriatal hypoxanthine administration on memory/ learning of rats in water-maze and step-down inhibitory avoidance tasks. The motor activity of the rats was evaluated by open field task. Results showed that hypoxanthine administration impaired memory/ learning in both tasks, however the motor activity of rats was not altered. Taken together, our results showed that intrastriatal hypoxanthine administration induced various biochemical and behavioral modification that could contribute, at least in part, to the characteristically neurological dysfunction observed in this syndrome. Moreover, if our evidences also occur in human, supplementation with antioxidants, like vitamins E and C, could be used as therapeutically strategies in order to avoid the neurological disturbances present in Lesch Nyhan patients.
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Julita, Emeline. "Modélisation de la dysfonction des neurones dopaminergiques associée à la maladie de Lesch-Nyhan à l'aide des cellules souches induites à la pluripotence". Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLE047.
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La maladie de Lesch-Nyhan (MLN) est une maladie rare dont la prévalence est estimée à une naissance sur 380 000. Il s’agit d’une maladie métabolique d’origine génétique liée au chromosome X, impliquant le gène de la HGPRT (hypoxanthine-guanine-phosphoribosyl-transférase). Les mutations dans ce gène entrainent un déficit d’activité de l’enzyme qui joue un rôle central dans le métabolisme des purines. Cette baisse d’activité provoque un défaut de fonctionnement de la voie de recyclage des purines induisant l’accumulation d’acide urique dans les articulations (goutte) et les reins (lithiase) qui peut être contrôlée par la prise d’allopurinol. En revanche, ces symptômes sont généralement accompagnés de troubles neurologiques quant à eux encore totalement inexpliqués et non traités. Ces derniers se traduisent par un handicap moteur important avec des mouvements anormaux (dystonie) et des troubles du tonus (hypotonie axiale). Dans les cas les plus graves des troubles du comportement peuvent également survenir se manifestant par des évènements importants d'automutilation (morsure des lèvres et des doigts). Des études menées en imagerie cérébrale, ont permis d’identifier chez les malades une diminution de la concentration cérébrale en dopamine mais aucune étude n’a encore pu lier de façon évidente le déficit en dopamine et la HGPRT, rendant difficile le développement de thérapies efficaces. L’objectif de ce travail a été de tirer avantage des propriétés d’auto renouvellement et de pluripotence des cellules souches induites à la pluripotence humaines (iPSC) pour produire d'authentiques neurones dopaminergiques (nDA) puis de les utiliser afin de déterminer dans quelle mesure la HGPRT est essentielle au développement et à l’homéostasie des nDA. Pour cela nous avons sélectionnés des fibroblastes obtenus à partir de biopsie de peau d’enfants atteints par la MLN que nous avons reprogrammé en iPSC. Ces iPSC ont été caractérisées et en particulier, l’expression protéique et l’activité enzymatique de la HGPRT a été contrôlée afin de valider notre modèle pathologique. Un protocole de différenciation de neurones dopaminergiques à partir d’iPSC a ensuite été mis au point pour permettre l’étude des différents stades de développement des neurones DA. Celui-ci permet d’obtenir des précurseurs exprimant pour 60% des cellules les marqueurs caractéristiques des précurseurs du mésencéphale ventral (MV), tout en respectant les différentes étapes clés du développement des nDA. Après l’induction de la différenciation des précurseurs en neurones, la population neuronale est composée d’au moins 20% de nDA exprimant les deux enzymes de la voie de synthèse de la dopamine TH et AADC. Ces différentes étapes du développement des nDA ont ensuite été analysées en comparant des cellules porteuses de mutations associées à la MLN et des cellules contrôles. Une anomalie neuro-développementale survenant à un stade précoce de la formation des nDA a été identifiée. Lors de l’étape ultime de différenciation, la proportion de précurseurs du MV capables de sortir du cycle cellulaire et donnant des neurones matures est plus faible dans les cultures de cellules porteuses des mutations MLN. Cette étude a permis dans un premier temps de démontrer qu’il était possible de modéliser une maladie impactant un gène essentiel dans le métabolisme à l’aide des iPSC. De plus, nous avons montré qu’il est possible d’identifier l’étape critique dans la genèse des nDA en utilisant des neurones humains dérivés d’iPSC issus d’enfants atteints de MLN. Cette approche apporte ainsi une meilleure compréhension sur les mécanismes responsables de la pathologie, et de nouveaux axes de recherche pour des approches thérapeutiquesLesch-Nyhan disease (LND) is a rare genetic disease with a prevalence estimated to 1:380,000. LND is a metabolic Xchromosome linked disorder that essentially affects boys and involves HGPRT gene (hypoxanthine-guanine phosphoribosyltransferase). Mutations in this gene result in a deficit of enzyme activity that plays a central role in the metabolism of purines. This activity deficiency induces a dysfunction on purine recycling pathway and promotes accumulation of uric acid in the joints (gout) and kidneys (stones) controlled using allopurinol. Next to these metabolic symptoms are neurological disorders which are not understood and efficiently controlled. These involve abnormal movements (dystonia) and low tonus (axial hypotonia). A unique feature of LND is the occurrence of self-injurious behaviors known as SIB (biting of lips and fingers). Brain imaging studies have revealed in LND patient a decrease of cerebral dopamine concentration but no study has yet been able to clearly link dopamine defect and HGPRT loss of activity, making it difficult to develop effective therapies. The aim of my study was to take advantage of the self-renewal and pluripotency properties of human induced pluripotent stem cells (iPSC) to produce dopaminergic neurons (nDA), then to use them to determine in which extend HGPRT is essential to the development and homeostasis of nDA. To that purpose, we selected fibroblasts obtained from skin biopsies of LND children that we have reprogrammed into iPSC. These iPSC were characterized and in particular, protein expression and enzymatic activity of HGPRT was assessed to validate our pathological model. We developed a protocol to differentiate dopaminergic neurons from iPSC to allow the study of different stages of nDA development. It provides mature precursors of nDA, expressing the typical marker of ventral midbrain (VM), while respecting the different key stages of nDA development. Upon terminal differentiation, these precursors produce at least 20% of nDA that express the two main enzymes of the dopamine synthesis pathway, namely TH and AADC. These different stages of nDA development were analyzed comparing LND and control IPSC. Neurodevelopmental abnormality occurring at an early stage of nDA formation was identified. At the final stage of differentiation, the proportion of MV precursors able to exit the cell cycle and differentiate as mature neurons is lower in LND culture compared to controls. This study provided evidences that it is possible to model a metabolic disease with iPSC and that they are essential tools to study neurodevelopmental disorders. This approach provides a better understanding of mechanisms responsible for the disease, and new research directions for therapeutic approaches
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Marques, Catarina Sofia Ribeiro. "Oximetria tecidular em doentes com insuficiência cardíaca NYHA classe III/IV". Master's thesis, Universidade da Beira Interior, 2012. http://hdl.handle.net/10400.6/1223.
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Introdução: Este trabalho de investigação pretende testar se a oximetria tecidular detecta a insuficiência cardíaca avançada estável relativamente à população sem doença, se valores mais baixos de oximetria tecidular estarão associados à descompensação da insuficiência cardíaca avançada e se é possível estimar um cut-off de oximetria tecidular abaixo do qual haja previsão de doença. Pretende avaliar se existe alguma correlação entre a oxigenação tecidual e os tipos de Insuficiência Cardíaca.
Métodos: De 14 de Novembro de 2011 a 24 de Dezembro de 2011 mediu-se a saturação em oxigénio da hemoglobina tecidular (StO2) na eminência hipotenar a indivíduos internados por descompensação aguda da Insuficiência Cardíaca NYHA III/IV, no dia em que tinham alta hospitalar. Decorridos 2 meses, pesquisou-se na base de dados ALERT® ER a presença de doença e se o óbito ou a hospitalização ocorreram. Comparou-se a média da StO2 com o valor de referência da população e compararam-se as médias de StO2 entre indivíduos doentes e não doentes, entre hospitalizados e não hospitalizados e entre os tipos de Insuficiência Cardíaca. Testou-se a associação entre a presença de doença e a oximetria tecidular. Elaborou-se a curva ROC®.
Resultados: Dos 39 indivíduos, 12 adoeceram devido a descompensação da Insuficiência Cardíaca, sendo que 9 foram hospitalizados e desses, 2 faleceram. Pacientes com Insuficiência cardíaca estável têm valores de StO2 (77,54±0,864) inferiores à população sem doença (p-value 0,0). Não existiu diferença entre as médias de StO2 entre indivíduos doentes e não doentes, entre hospitalizados e não hospitalizados e entre os tipos de Insuficiência cardíaca. Não existiu associação entre valores baixos de StO2 e a presença de doença. A realização do teste de oximetria tecidular não é melhor que o acaso na previsão da doença curva ROC (p-value 0,681).
Conclusão: A população com Insuficiência Cardíaca estável tem valores de oximetria tecidular mais baixos que a população sem doença. Não se obteve associação entre a oximetria tecidular e a presença de doença. A oximetria tecidular não identificou um subgrupo de doentes com IC em maior risco de descompensação.
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CASTELLI, ALESSANDRA. "CORRECTION OF AN X-LINKED GENETIC DEFECT BY MICROCELL-MEDIATED CHROMOSOME TRANSFER". Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/229559.
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Several approaches to the correction of genetic defects have been investigated in the last two decades, including those based on retroviral and lentiviral vectors. Although viral vectors are a powerful instrument for gene therapy and are being used in human trials, they present drawbacks such as risk of insertional mutagenesis and limited insert size. Homologous recombination techniques, which has long been applied to mouse stem cell engineering, have recently been used in combination with novel tools exploited the activity of nucleases coupled to targeting methods such those based on zinc fingers, TALEN and CRISPR, which allow targeting to specific DNA sequences to a great extent. However some genetic defects, and in particular genomic abnormalities such as large deletions, are not suitable to correction with these tools. Here I suggest that large structural abnormalities of the X chromosome can be treated by chromosome transfer mediated by microcells (MMCT). The rationale underlying my work was the fact that by MMCT all the sequences and structures needed for proper expression of the affected gene(s) are transferred into the defective cell and no non-human sequence is added to the cell. Furthermore, additional X chromosomes are usually silenced and cells with more than two X chromosomes are essentially normal, as shown by XXX trisomic human organisms.
Therefore, MMTV has the potential to correct several diseases whose underlying abnormality lies on the X chromosome. With this aim in mind, we devised an in vitro model to show the feasibility of the approach. Our plan was to transfer an exogenous X chromosome into the embryonic stem cell (ESC) line HM1 which is defective in the hprt gene, whose mutation in humans cause the Lesch-Nyhan syndrome, a severe neurological pathology. A mouse normal chromosome was transferred from normal MEF to the A9 cell line, a neoplastic cell which has a great capability to form micronuclei. The HM1 was the recipient cell line, while the A9-X was the donor one. The A9-X cells were micronucleated and microcells of small size were filtered and fused to HM1 cells in the presence of PEG. Cells were cultured in HAT medium, which selects for the expression of a correct HPRT protein by the fused cells. A few colonies were obtained and their karyotype was determined to be XXY. These cells showed the presence of a correct HPRT transcript and grow in the selective HAT medium. These results suggest that a single chromosome can be transferred to ESC line in order to correct the genetic anomaly and opens the way to the correction of more complex structural abnormalities of the X chromosome, such as that associated to the fragile X.
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Brendler, Helena Biasibetti. "Administração intraestriatal de hipoxantina altera perfil inflamatório e neuroenergético via estresse oxidativo em estriado de ratos". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/159510.
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A hipoxantina, principal oxipurina envolvida na via de salvação das purinas no cérebro, acumula-se na doença de Lesch-Nyhan, um erro inato do metabolismo das purinas. Os sintomas clínicos manifestam-se precocemente na vida dos pacientes, incluindo alterações motoras e cognitivas, retardo mental e automutilação. Embora os mecanismos subjacentes da disfunção cerebral na doença de Lesch-Nyhan sejam pouco compreendidos, o acúmulo de hipoxantina parece contribuir para os danos neurológicos. O objetivo deste estudo foi investigar os efeitos da administração intraestriatal de hipoxantina em ratos infantis e adultos jovens submetidos à cirurgia estereotáxica. Neste estudo, analisamos primeiramente o efeito da hipoxantina sobre os parâmetros neuroinflamatórios e oxidativos em estriados de ratos infantis e adultos jovens. Foram avaliados também alguns parâmetros neuroenergéticos. Ratos Wistar de 21 e 60 dias de vida foram submetidos à cirurgia estereotáxica e foram divididos em dois grupos: controle (infusão de solução salina 0,9%) e hipoxantina (10 IJM). A administração intraestriatal de hipoxantina aumentou os níveis de IL-6 e TNF-a e o imunoconteúdo da subunidade NF-kB I p65 nuclear em estriado de ambas as idades de ratos. A ativação microglial e astrocitária foram observadas pelo aumento do imunoconteúdo de lba1 e GFAP, respectivamente, no estriado de ratos de 21 dias. Todos os parâmetros oxidativos foram alterados, sugerindo uma forte relação neurotóxica de hipoxantina e estresse oxidativo. Em ratos de 60 dias de vida, a hipoxantina aumentou a atividade da succinato desidrogenase e do complexo 11 e diminuiu a atividade da citocromo c oxidase e seu imunoconteúdo. A injeção de hipoxantina diminuiu a porcentagem marcação de membrana mitocondrial e aumentou marcação de potencial mitocondrial. A hipoxantina também diminuiu o número de células vivas e aumentou o número de células apoptóticas. Em ratos de 21 dias de vida, a hipoxantina alterou alguns parâmetros do metabolismo energético e diminui a atividade de Na+,K+-ATPase, provavelmente por danos às proteínas, visto pela redução de conteúdo de sulfidrilas. Nossos achados mostram que a administração de hipoxantina alterou parâmetros neuroinflamatórios e neuroenergéticos, possivelmente por meio de desequilíbrio oxidativo, sugerindo que esses processos podem estar envolvidos, pelo menos em parte, com os distúrbios neurológicos encontrados em pacientes com doença de Lesch-Nyhan.Hypoxanthine, the major oxypurine metabolite involved in purine's salvage pathway in the brain, is accumulated in Lesch-Nyhan disease, an in bom errar of metabolism of purine. The clinicai symptoms manifest early in the patients' lives, including motor and cognitiva alterations, mental retardation and self-mutilation. Although the underlying mechanisms of brain dysfunction in Lesch-Nyhan disease are poorly understood, the accumulation of hypoxanthine appears to contribute to neurological damage. The purpose of this study was to investigate the effects of hypoxanthine intrastriatal administration in infant and young adult rats submitted to stereotactic surgery. We firstly analyzed the effect of hypoxanthine on neuroinflammatory and oxidative parameters in striatum of infant and young adult rats. We also evaluated some neuroenergetic parameters. Wistar rats of 21 and 60 days of life underwent stereotactic surgery and were divided into two groups: contrai (infusion of saline 0.9%) and hypoxanthine (10 IJM). lntrastriatal administration of hypoxanthine increased IL- 6 and TNF-a leveis and nuclear immunocontent of NF-KB/p65 subunit in striatum of rats of both ages. Microglial and astrocyte activation was seen by the increase in lba1 and GFAP immunocontent, respectively, in striatum of infant rats. Ali oxidative parameters were altered, suggesting a strong neurotoxic hypoxanthine role on oxidative stress. In 60-day-old rats hypoxanthine increased succinate dehydrogenase and complex 11 activities and diminished cytochrome c oxidase activity and immunocontent. Hypoxanthine injection decreased the percentage of cells with mitochondrial membrana label and increased mitochondrial mass potential labeling. Hypoxanthine also diminished the number of live cells and increased the number of apoptotic cells. In 21-days-old rats hypoxanthine altered some energy metabolism parameters and decreased Na•,K•-ATPase activity probably by protein damage, seen in the reduction of sulfhydryl content. Our findings show that the administration of hypoxanthine altered neuroinflammatory and neuroenergetic parameters, possibly through oxidative imbalance, suggesting that these processes may be involved, at least in part, with the neurological disorders found in patients with Lesch-Nyhan disease.
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Carlsson, Eric, i Kristoffer Falstad. "Patienters vardagliga upplevelse av att leva med kronisk hjärtsvikt : En litteraturöversikt". Thesis, Hälsohögskolan, Högskolan i Jönköping, HHJ, Avd. för omvårdnad, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-35719.
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Bakgrund: Hjärtsvikt är vanligt förekommande, ca 26 miljoner i världen och 250 000 i Sverige lever med diagnosen. Hjärtsvikt är ett komplext tillstånd med påverkan på många olika delar av livet. Behandlingen för hjärtsvikt är även detta komplext och att se individens situation är viktigt för framgångsrik behandling. Syfte: Att beskriva patienters upplevelse av att leva med kronisk hjärtsvikt i vardagen. Metod: En litteraturöversikt med 13 kvalitativa artiklar inkluderade de har analyserats med Fribergs femstegsmodell. Resultat: Resultatet visar på hur patienter med hjärtsvikt upplever att deras vardagliga liv har blivit förändrat av hjärtsvikt. Hur de upplever de nödvändiga förändringar de gör för att hantera en vardag med hjärtsvikt. Resultatet presenteras i kategorierna; stöd och kraft från omgivningen, mötet med sjukvården, rädsla samt förändringar i vardagen. Slutsats: Att leva med kronisk hjärtsvikt innebär en påverkan på patientens vardag. Social isolering, trötthet, andnöd, fysiska begränsningar och rädsla inför framtiden är några av de upplevelser som framkommer vid hjärtsvikt. Sjuksköterskan har här möjligheter att stötta och informera patienten att skapa förutsättningar att hantera vardagen med hjärtsvikt.Background: Heart failure is a common condition, about 26 million in the world and 250 000 in Sweden are living with the diagnosis. Heart failure is a complex condition and have effects on many parts of life. Treatment for heart failure is also complex and to see the individual’s situation is important for a successful treatment. Aim: To describe patients’ experience of living with heart failure in everyday life. Methods: A literature review with 13 studies included they have been analyzed with the Friberg Five Step-model. Results: The result shows that patients with heart failure experiences that their everyday life has changed because of heart failure. How they experience necessary changes they do to manage everyday life with heart failure. The results is presented in these categories; support and power from the surrounding, meeting the healthcare, fear and changes in everyday life. Conclusion: Living with chronic heart failure has an impact on the patient's daily life. Social isolation, fatigue, shortness of breath, physical limitations and fear of the future are some of the experiences that emerge in heart failure. The nurse has opportunities to support and inform the patient to create the conditions for managing everyday life with heart failure.
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Svensson, Helena, i Hilda Melander. "Fatigue i fem dimensioner : en enkätstudie om fatigue i relation till kön, NYHA-klass och EF-kategori hos personer med hjärtsvikt". Thesis, Sophiahemmet Högskola, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:shh:diva-3635.
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Antalet personer som lever med hjärtsvikt ökar. Fatigue är ett av de vanligaste symtomen vid hjärtsvikt och kan beskrivas som en överväldigande fysisk, kognitiv och känslomässig trötthet som inte kan lindras med normala återhämtningsmetoder. Trots att fatigue har stor negativ påverkan på livskvalitet och egenvård uppmärksammas det sällan i lika stor utsträckning som övriga symtom vid hjärtsvikt. För att sjuksköterskor ska kunna erbjuda personcentrerad omvårdnad till denna komplexa och växande patientgrupp krävs ökad kunskap om hur fatigue tar sig uttryck hos personer med hjärtsvikt. Syftet med denna studie var att beskriva förekomst av fem olika dimensioner av fatigue i relation till kön, NYHA-klass och EF-kategori hos personer med hjärtsvikt. Metoden för studien var kvantitativ, med en induktiv ansats och icke-experimentell design. Datainsamlingen utfördes med hjälp av The Multidimensional Fatigue Inventory (MFI-20), en validerad enkät som identifierar fem olika dimensioner av fatigue; generell fatigue, fysisk fatigue, mental fatigue, minskad motivation och minskad aktivitet. Genom ett konsekutivt urval inkluderades 92 personer som besvarade MFI-20 i samband med ett besök på en dagvårdsmottagning för hjärtsvikt. MFI-20-enkäterna analyserades med hjälp av det statistiska mjukvaruprogrammet SPSS. Resultatet i denna studie visade att kvinnor uppgav signifikant högre nivåer av fatigue än män i tre av fem dimensioner. Oavsett kön uppgavs högst nivåer i dimensionen fysisk fatigue. Vidare indikerade resultatet att personer med högre NYHA-klass uppgav högre nivåer av fatigue och personer med HFpEF uppgav högre nivåer av fatigue än de med HFrEF. Slutsatsen är att sjuksköterskor behöver arbeta utifrån vetskapen om att fatigue är vanligt förekommande hos personer med hjärtsvikt, i signifikant högre nivåer hos kvinnor än hos män. Studiedeltagarna uppgav högst nivåer av fysisk fatigue, och omvårdnad och patientinformation behöver utformas därefter. Genom personcentrerad omvårdnad kan sjuksköterskor uppmärksamma fatigue och stötta varje person i dennes egenvård i takt med sjukdomsprogressionen. Rutiner och effektiva instrument behöver utvecklas för att kunna bedöma fatigue och utvärdera tillhörande omvårdnadsåtgärder. Vidare forskning krävs kring varför personer med bevarad pumpförmåga uppgett högre nivåer av fatigue än de med nedsatt pumpförmåga.The prevalence of persons with heart failure is increasing. Fatigue is one of the most common symptoms of heart failure and can be described as an overwhelming physical, cognitive and emotional tiredness that is not relieved by normal recovery strategies. Despite the fact that fatigue has a negative impact on quality of life and self care, it rarely receives the same attention as other heart failure symptoms. To enable nurses to offer a patient- centered care to this complex and growing group of patients, increased knowledge concerning how fatigue is affecting persons with heart failure is needed. The aim of the study was to describe five dimensions of fatigue in relation to gender, NYHA-class and EF-category among persons with heart failure. The method of the study was quantitative, with an inductive approach and non- experimental design. Data collection was performed using The Multidimensional Fatigue Inventory (MFI20), a validated questionnaire which identifies five dimensions of fatigue; general fatigue, physical fatigue, mental fatigue, reduced motivation and reduced activity. Through a consecutive sample 92 participants were included and answered MFI-20 during an visit at a heart failure outpatient clinic. The MFI-20 questionnaires were analyzed using the statistical software program SPSS. The result of this study showed that women reported significantly higher levels of fatigue than men in three out of five dimensions. Regardless of gender the highest levels were reported in physical fatigue. Furthermore the result showed that worse NYHA-categories was associated with higher levels of fatigue. Study participants with HFpEF reported higher levels of fatigue than participants with HFrEF. The conclusion is that nurses need to base their work on the knowledge that fatigue is a common symptom in persons with heart failure, with significantly higher levels in in women than in men. Study participants reported higher levels of physical fatigue, and nursing care and patient information should be designed accordingly. Through patient- centered care nurses can identify fatigue and support patient self care as the heart failure progress. Development of routines and effective instruments is needed to assess fatigue and evaluate nursing care, as well as further research concerning fatigue in persons with HFpEF.
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Salman, Ali MD. "Depressive Symptoms, Quality of Life, and Vitamin Supplements in Ambulatory Heart Failure Patients". Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1212769869.
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Del, Rio Reina. "Quality of Life and Hospital Readmissions among Patients with NYHA Class III Heart Failure Following Implantation of Cardiomems(TM) Sensor| A Mixed Methods Study". Thesis, Sage Graduate School, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10974669.
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Heart failure is a disease with high morbidity and mortality in the U.S. and globally. There are about 5.7 million people in the U.S with heart failure, and about 10 million in Europe. The disease is present more frequently in patients over 65 years old. Data from the ongoing Framingham Heart Study has shown that the one-year mortality rate is 22% and the 5-year mortality rate is 42%. While there have been significant advancements in the care of patients with heart failure, there is still no cure. In addition, Medicare has estimated that the number one cause for hospital admissions in the U.S. is heart failure, according to ICD-9 and ICD-10 reimbursement codes.
The CardioMEMS™ Heart Failure System is the first implantable device in the U.S. that has shown to decrease the number of HF-related hospital readmissions in patients implanted with the sensor and reported in the original CHAMPION trial. This study focused upon the evaluation of HF patients’ perception of quality of life and whether there was a statistically significant decrease in the number of HF-related hospital readmissions among those implanted with the CardioMEMS™ sensor.
This study was conducted in three phases: one qualitative and two quantitative phases. The qualitative aspect included individual interviews with NYHA Class III HF patients who had the CardioMEMS™ sensor implanted.
Qualitative study findings revealed that patients with HF experienced fatigue that impacted their activities of daily living, particularly those involving family. It also revealed that despite the fact that none of the respondents had been hospitalized for a HF-related reason, most did not perceive an improvement in their quality of life since implantation of the CardioMEMS™ sensor based on individual participant interviews.
The first quantitative aspect of the study assessed the perception of quality of life of these same patients based upon individual MLFHQ scores. Findings from MLHFQ results revealed that there was a negative impact in respondents’ quality of life, particularly in the physical dimensions of the MLHFQ. Interestingly, those scores were somewhat lower than what is found in the literature.
The second of the quantitative phase analyzed the number of HF-related hospital admissions in patients with the CardioMEMS™ sensor based on a 1:28 retrospective case-control matching study design. Analysis showed that patients implanted with the CardioMEMS™ sensor had a statistically significant decrease in the number of HF-related hospital admissions. Incidental findings also showed a statistically significant decrease in the number of HF-related hospital readmissions in patients with NYHA Class III HF after implantation of the CardioMEMS™. This is compelling evidence of the need for further studies in this new technology and its impact on patients with NYHA Class III HF.
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Buck-Müller, Nina. "Einfluss des beta-Rezeptorantagonisten Nebivolol auf hämodynamische Parameter, Verträglichkeit und Lebensqualität bei Patienten mit chronischer Herzinsuffizienz der NYHA-Klasse II und III zur Basistherapie (Herzglykosid, ACE-Inhibitor, Diuretikum)". [S.l. : s.n.], 2002. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB10236389.
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Lein, Fong-Ron, i 連峰榮. "The Effects of HPRT on Lesch-Nyhan Syndrome". Thesis, 1996. http://ndltd.ncl.edu.tw/handle/07650896623502684674.
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Hobman, Tom C. "Molecular studies in two unrelated Lesch-Nyhan Syndrome families". 1987. http://hdl.handle.net/1993/24438.
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Shao, Shiao-Wen, i 邵筱雯. "The illness representation mediate the relationship between NYHA functional classification and quality of life in heart failure patients". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/53myy5.
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碩士國立陽明大學
臨床暨社區護理研究所
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Heart failure (HF) is the final common sign of all kinds of heart diseases, and the prevalence is continuously elevated followed by aging and medical progression. Along with the development of medical profession, the goal of treatments is no longer extending human lives, but alleviating symptoms and improving functions, thus enhancing the quality of life (QoL). There are more and more investigations for the QoL of people with HF, but in those researches studying the related factors of improving QoL, the effectiveness is still not good enough. Therefore, we utilized the self-regulation model stated by Leventhal in 2003 which mentioned that patients will give illness representations to those stimulations of diseases and then have coping behaviors and outcome appraisals, to investigate the relationships between disease characteristics and illness representations, and the mediating influences of illness representations to disease characteristics and QoL in patients with HF. Seventy-six.NYHA I to IV HF subjects were recruited from an internal cardiology ward of one northern medical centerby purposive sampling methodand cross-sectional study. Research data were collected by Illness Representation Questionnaire and Minnesota Living With Heart Failure Questionnaire (MLWHFQ) Chinese version, and sorted and analyzed by SPSS 20.0. Hierarchical linear regression analysis was used to determine the correlations, and Sobel test was used to determine the mediating relationship. The results showed that NYHA functional classification was highly significantly correlated with all 7 dimensions of illness representations and QoL (all p <.001), and all 7 dimensions of illness representations were significantly correlated with QoL (all p <.01). NYHA functional classification and illness representationsare the predictors for QoL. The results of hierarchical linear regression showed the R2 of NYHA functional classification to QoL was .27, the R2 of illness representations to QoL was .44. The results of Sobel test showed that 5 dimensions (timeline acute/chronic, timeline cyclical, illness consequences, personal control and emotional representation) of illness representations were revealed partial mediating influences between NYHA functional classification and QoL. NYHA functional classification is not only correlated with QoL, but affects QoL via illness representations indirectly. Our research results can help nursing professionals to understand such patients’ illness representations, and provide a reference for the care and intervention of the future. Therefore, we suggest that if medical and nursing professionals would like to improve patients’QoL, they should not only focus on patients’ physiological symptoms, but have to understand patients’ illness representations, and thus can enhance QoL effectively.
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Klein, Anne-Kathrin [Verfasser]. "Humane autologe intrakoronare Stammzelltransplantation zur Myokardregeneration bei dilatativer Kardiomyopathie (NYHA-Stadium II bis III) / vorgelegt von Anne-Kathrin Klein". 2010. http://d-nb.info/1010986678/34.
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Durstewitz, Kathleen. "Einfluss von typischen Komorbiditäten auf die Ausprägung der Symptomatik bei Herzinsuffizienz mit eingeschränkter und erhaltener linksventrikulärer Funktion". Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-000D-F02A-D.
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Cardoso, Bárbara de Pinho. "Clínicas de insuficiência cardíaca : indicações e resultados". Master's thesis, 2009. http://hdl.handle.net/10316/33594.
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Trabalho final do 6º ano médico com vista à atribuição do grau de mestre no âmbito do ciclo de estudos de mestrado integrado em medicina da Faculdade de Medicina de Coimbra.A. Introdução: Numerosos estudos são unânimes ao demonstrar o impacto das Clínicas de insuficiência cardíaca na melhoria da qualidade de vida e estado funcional de doentes com insuficiência cardíaca grave, a par da redução das suas taxas de re-hospitalização e dos custos. B. Objectivos: Verificação, em duas Clínicas de insuficiência cardíaca portuguesas, do impacto positivo descrito na literatura internacional relativamente às taxas de prescrição médica, parâmetros clínicos e número de internamentos por insuficiência cardíaca. C. Métodos. 1. Concepção: Estudo retrospectivo e multicêntrico. 2. População e contexto: Analisámos dados relativos a doentes com insuficiência cardíaca sistólica (Fracção de ejecção ventricular esquerda ≤ 40%) seguidos nas consultas de insuficiência cardíaca dos serviços de cardiologia dos Hospitais de S. João, Porto e da Universidade de Coimbra. 3. Intervenção: Optimização da terapêutica farmacológica segundo as recomendações internacionais. Educação e aconselhamento dos doentes, visando o aumento da adesão à terapêutica. 4. Avaliação: Comparámos a terapêutica instituída, a fracção de ejecção ventricular esquerda e a classe funcional da New York Heart Association à data da primeira versus a última consulta. Foram ainda comparados o número de internamentos por insuficiência cardíaca ocorridos nos seis meses anteriores à admissão à Clínica versus os registados nos seis meses antes da data da última consulta. D. Resultados: Foram integrados no estudo 201 doentes com insuficiência cardíaca sistólica [162 (81%) ♂ e 39 (19%) ♀; idade 55 ± 14; etiologia isquémica: 35% e etiologia não isquémica: 65%]. O tempo médio de seguimento foi de 4.9 ± 3.6 anos, no final do qual se registou um aumento significativo das taxas de prescrição de IECA/ARA (p<0.001), Bloqueadores-β (p<0.001), espironolactona (p<0.001) e digoxina (p=0.004). Não houve variação da frequência de prescrição de diuréticos (p=0.636). Comparativamente com a primeira consulta, à data da última verificou-se um aumento da fracção de ejecção ventricular esquerda (26 ± 7 versus 33 ± 13 , p<0.001) e uma melhoria da classe funcional (Classe da New York Heart Association 2.5 ± 0.9 versus 2.0 ± 0.8, p<0.001); Classe da New York Heart Association no final do seguimento I: 25%, II: 52%, III: 20%, IV: 3% versus Classe da New York Heart Association à data da primeira consulta I: 13%, II: 39%, III: 37%, IV: 11% (p<0.001). Registámos também uma diminuição muito significativa do número de hospitalizações por insuficiência cardíaca por doente (0.7 ± 0.8 versus 0.2 ± 0.5; p<0.001) nos seis meses anteriores à data da última consulta versus os seis meses anteriores à primeira. E. Conclusões: Nas duas clínicas analisadas, verificou-se, no final do seguimento, um aumento das taxas de prescrição de bloqueadores neuro-hormonais. Foi ainda registado um impacto positivo na limitação da progressão da doença e na diminuição do número de internamentos por descompensação da insuficiência cardíaca. A. Introduction: It has been demonstrated that heart failure disease management programs improve patients' quality of life and functional status while reducing the frequency of hospitalizations. B. Aims: To confirm, in two portuguese heart failure clinics, the positive impact on guidelinerecommended drug prescription rates, clinical outcomes and heart failure-related hospital readmission rates observed in international clinical trials. C. Methods. 1. Design: Retrospective, multicenter trial. 2. Patients and setting: Patients with systolic heart failure (Left ventricular ejection fraction ≤ 40%) were recruited from the heart failure clinics of two university hospitals (Hospital de S. João, Porto and Hospitais da Universidade de Coimbra). 3. Intervention: Optimization of drug therapy and comprehensive education and counseling, according to evidence-based heart failure practice and therapy guidelines. 4. Assessments: Comparison of heart failure drug prescription rates, left ventricular ejection fraction and functional status (New York Heart Association Class) at the time of the first visit versus the last visit. In addition, the number of heart failure-related hospital readmissions occured during the six months before the first visit versus those occured during the six months before the last visit, were compared. D. Results: Two hundred and one patients with systolic heart failure [162 (81%) ♂ e 39 (19%) ♀; mean age 55 ± 14 years old; ischemic ethiology: 35% and non-ischemic ethiology: 65%] were included in this study. After an average follow-up of 4.9 ± 3.6 years there was a significant improvement in ACEI/ARB (p<0.001), Beta-blockers (p<0.001), spironololactone (p<0.001) and digoxin (p=0.004) prescription rates. The prescription rate of diuretics did not increase (p=0.636). There was a significant improvement in left ventricular ejection fraction (26 ± 7 versus 33 ± 13 p<0.001). A reduction in patients' functional class was found (2.5 ± 0.9 versus 2.0 ± 0.8, p<0.001); New York Heart Association Class at the time of the last visit I: 25%, II: 52%, III: 20%, IV: 3% versus New York Heart Association Class at the time of the first visit I: 13%, II: 39%, III: 37%, IV: 11% (p<0.001). There was also a significant reduction in the number of heart failure hospitalizations/ patient (0.7 ± 0.8 versus 0.2 ± 0.5; p<0.001) occured during the six months before the first visit compared with the six months before the last visit. E. Conclusions: These two portuguese heart failure clinics proved to be effective in prescription rates of guideline-recomended heart failure drug therapies. Patients were shown to have significantly fewer heart failure rehospitalizations and improved left ventricular ejection fraction and functional status as compared to their preintervention status. Key Words: Systolic Heart failure, Heart failure clinics, Left ventricular ejection fraction, NYHA functional class, Heart failure-related hospital readmissions, Neurohormonal blockers.
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Hodapp, Antonia [Verfasser]. "Einfluss einer strukturierten, multimodalen, stationären Rehabilitations-Intervention auf NT-proBNP-Werte bei Patienten mit chronischer Herzinsuffizienz NYHA II-III : eine Multi-Center 6-Monats-Studie / vorgelegt von Antonia Hodapp geb. Schandelmeyer". 2009. http://d-nb.info/1003555195/34.
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Mušálková, Dita. "Molekulárně genetické a biochemické studie vybraných dědičných metabolických onemocnění, vývoj a aplikace nových metod". Doctoral thesis, 2016. http://www.nusl.cz/ntk/nusl-265169.
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Inherited metabolic disorders (IMD) form a diverse group of several hundred different diseases with a relatively high cumulative incidence (stated up to 1:600). They are associated with accumulation of the substrates and lack of the products in specific metabolic pathways, which is caused by deficiency of the enzyme or its activator, or dysfunction of the transport protein. However, the underlying cause is at the DNA level. The grounds for different phenotype manifestation in patients with the same genotype are often not known. During my work at the Institute of Inherited Metabolic Disorders, I designed several new methods for the research of IMD and applied them in the patients and their families. I created procedures for the isolation of lysosomal membranes that are used for the research of lysosomal storage disorders and general properties of lysosomes. Next, I introduced several novel assays for determination of the X-inactivation ratio, which led to a significant increase of informative women. Nowadays, we use these methods in heterozygous women with X-linked diseases in order to study the influence of X-inactivation on the manifestation of the diseases. The cases of a girl with mucopolysaccharidosis type II, a girl with OTC deficiency and a family with the mutation in HPRT1 gene are described...
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Buck-Müller, Nina [Verfasser]. "Einfluss des β-Rezeptorantagonisten [Beta-Rezeptorantagonisten] Nebivolol auf hämodynamische Parameter, Verträglichkeit und Lebensqualität bei Patienten mit chronischer Herzinsuffizienz der NYHA-Klasse II und III zur Basistherapie (Herzglykosid, ACE-Inhibitor, Diuretikum) / vorgelegt von Nina Buck-Müller". 2002. http://d-nb.info/965291502/34.
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Horduna, Irina. "La qualité de vie et la capacité fonctionnelle chez les patients atteints de fibrillation auriculaire et d'insuffisance cardiaque congestive". Thèse, 2011. http://hdl.handle.net/1866/6082.
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De déterminer si une stratégie de contrôle du rythme améliore la qualité de vie et / ou la capacité fonctionnelle par rapport à une stratégie de contrôle de la fréquence
cardiaque chez les patients atteints de fibrillation auriculaire et d'insuffisance cardiaque congestive.
Méthode:
Pour évaluer la qualité de vie, le questionnaire SF-36 a été administré à l'inclusion et à 4 mois chez 749 patients de l’étude AF-CHF. Les paramètres de capacité fonctionnelle évalués ont été la classe fonctionnelle NYHA (1376 patients) et la distance de marche de six minutes (1099 patients).
Résultats:
Le type du traitement assigné n'a pas eu un impact significatif sur la qualité de vie ou la capacité fonctionnelle.
Conclusion:
La qualité de vie et la capacité fonctionnelle sont similaires chez les patients randomisés au contrôle du rythme par rapport au contrôle de la fréquence. Les hommes non-obèses avec moins de comorbidités semblent plus susceptibles de s'améliorer.To determine if a rhythm control strategy improves quality of life and/or functional capacity compared to a rate control strategy in patients with atrial fibrillation and congestive heart failure. Methods: To assess QoL, the Medical Outcomes Short Form-36 (SF-36) was administered to 749 patients included in the AF-CHF study at baseline and at 4 months. Functional capacity was assessed by NYHA class determined at baseline, 3 weeks, 4 months, and at 4-month intervals thereafter in 1376 patients and by 6 minutes walk test conducted at baseline, 3 weeks, 4 months, 1 year, and annually thereafter in 1099 patients. Results: The type of the assigned treatment had no significant impact on quality of life scores nor on functional capacity. Conclusion: Quality of life and functional capacity improved to a similar extent in patients randomised to rhythm versus rate-control strategies. Non-obese male patients with less comorbidities seem more likely to improve.