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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
141

Mapping the methylation status of the miR-145 promoter in saphenous vein smooth muscle cells from individuals with type 2 diabetes

Riches-Suman, Kirsten, Huntriss, J., Keeble, C., Wood, I.C., O'Regan, D.J., Turner, N.A., Porter, K.E. 2016 December 1921 (has links)
Yes / Type 2 diabetes mellitus prevalence is growing globally, and the leading cause of mortality in these patients is cardiovascular disease. Epigenetic mechanisms such as microRNAs (miRs) and DNA methylation may contribute to complications of type 2 diabetes mellitus. We discovered an aberrant type 2 diabetes mellitus–smooth muscle cell phenotype driven by persistent up-regulation of miR-145. This study aimed to determine whether elevated expression was due to changes in methylation at the miR-145 promoter. Smooth muscle cells were cultured from saphenous veins of 22 non-diabetic and 22 type 2 diabetes mellitus donors. DNA was extracted, bisulphite treated and pyrosequencing used to interrogate methylation at 11 CpG sites within the miR-145 promoter. Inter-patient variation was high irrespective of type 2 diabetes mellitus. Differential methylation trends were apparent between non-diabetic and type 2 diabetes mellitus–smooth muscle cells at most sites but were not statistically significant. Methylation at CpGs −112 and −106 was consistently lower than all other sites explored in non-diabetic and type 2 diabetes mellitus–smooth muscle cells. Finally, miR-145 expression per se was not correlated with methylation levels observed at any site. The persistent up-regulation of miR- 145 observed in type 2 diabetes mellitus–smooth muscle cells is not related to methylation at the miR-145 promoter. Crucially, miR-145 methylation is highly variable between patients, serving as a cautionary note for future studies of this region in primary human cell types.
142

MicroRNA‐21 drives the switch to a synthetic phenotype in human saphenous vein smooth muscle cells

Alshanwani, A.R., Riches-Suman, Kirsten, O'Regan, D.J., Wood, I.C., Turner, N.A., Porter, K.E. 2018 April 1916 (has links)
Yes / Cardiovascular disease is a leading cause of morbidity and mortality. Smooth muscle cells (SMC) comprising the vascular wall can switch phenotypes from contractile to synthetic, which can promote the development of aberrant remodelling and intimal hyperplasia (IH). MicroRNA‐21 (miR‐21) is a short, non‐coding RNA that has been implicated in cardiovascular diseases including proliferative vascular disease and ischaemic heart disease. However, its involvement in the complex development of atherosclerosis has yet to be ascertained. Smooth muscle cells (SMC) were isolated from human saphenous veins (SV). miR‐21 was over‐expressed and the impact of this on morphology, proliferation, gene and protein expression related to synthetic SMC phenotypes monitored. Over‐expression of miR‐21 increased the spread cell area and proliferative capacity of SV‐SMC and expression of MMP‐1, whilst reducing RECK protein, indicating a switch to the synthetic phenotype. Furthermore, platelet‐derived growth factor BB (PDGF‐BB; a growth factor implicated in vasculoproliferative conditions) was able to induce miR‐21 expression via the PI3K and ERK signalling pathways. This study has revealed a mechanism whereby PDGF‐BB induces expression of miR‐21 in SV‐SMC, subsequently driving conversion to a synthetic SMC phenotype, propagating the development of IH. Thus, these signaling pathways may be attractive therapeutic targets to minimise progression of the disease. / King Saud University; College of Medicine , Riyadh, Saudi Arabia
143

Role of microRNA-145 in DNA damage signalling and senescence in vascular smooth muscle cells of Type 2 diabetic patients

Hemmings, K.E., Riches-Suman, Kirsten, Bailey, M.A., O'Regan, D.J., Turner, N.A., Porter, K.E. 05 May 2021 (has links)
Yes / Increased cardiovascular morbidity and mortality in individuals with type 2 diabetes (T2DM) is a significant clinical problem. Despite advancements in achieving good glycaemic control, this patient population remains susceptible to macrovascular complications. We previously discovered that vascular smooth muscle cells (SMC) cultured from T2DM patients exhibit persistent phenotypic aberrancies distinct from those of individuals without a diagnosis of T2DM. Notably, persistently elevated expression levels of microRNA-145 co-exist with characteristics consistent with aging, DNA damage and senescence. We hypothesised that increased expression of microRNA-145 plays a functional role in DNA damage signalling and subsequent cellular senescence specifically in SMC cultured from the vasculature of T2DM patients. In this study, markers of DNA damage and senescence were unambiguously and permanently elevated in native T2DM versus non-diabetic (ND)-SMC. Exposure of ND cells to the DNA-damaging agent etoposide inflicted a senescent phenotype, increased expression of apical kinases of the DNA damage pathway and elevated expression levels of microRNA-145. Overexpression of microRNA-145 in ND-SMC revealed evidence of functional links between them; notably increased secretion of senescence-associated cytokines and chronic activation of stress-activated intracellular signalling pathways, particularly the mitogen-activated protein kinase, p38a. Exposure to conditioned media from microRNA-145 overexpressing cells resulted in chronic p38a signalling in naïve cells, evidencing a paracrine induction and reinforcement of cell senescence. We conclude that targeting of microRNA-145 may provide a route to novel interventions to eliminate DNA-damaged and senescent cells in the vasculature and to this end further detailed studies are warranted.
144

Identification of functional enhancers at open chromatin regions involved in sex specificity and xenobiotic metabolism using in vivo STARR-seq in mouse livers

Chang, Ting-Ya 20 September 2024 (has links)
Enhancers regulate gene expression through epigenetic mechanisms influenced by internal and external stimuli. In mouse liver, growth hormone and environmental chemical exposures activate enhancers regulating gene expression in part through changes in chromatin accessibility. Identifying functional enhancers in the complex environment of mouse liver is challenging. This thesis presents HDI-STARR-seq, a massively parallel STARR-seq reporter assay that combines hydrodynamic injection (HDI)-driven plasmid delivery to mouse liver cells in vivo with expression from the liver-specific Albumin promoter to assay functional changes in enhancer-driven transcription induced by sex-dependent hormonal stimulation and xenobiotic exposure. HDI-STARR-seq employs a minimal albumin promoter, shows minimal innate immune response and apparently facilitates plasmid chromatinization recapitulating endogenous liver chromatin states. The assay is robustly reproducible in a small reporter library (~100 regions) and can be scalable for genome-wide analysis using 25,000-50,000 synthetic DNA fragments or enzyme-released mouse liver genomic fragments. Single nucleus-based 10x Genomics Multiome analysis identified accessible mouse liver chromatin regions genome-wide, their linked target genes in hepatocytes, and their differential accessibility between sexes and following exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand. Using HDI-STARR-seq, functional enhancer activity was determined for 1,789 accessible chromatin regions across biological conditions, identifying many sex-biased, GH-regulated enhancers undergoing chromatin changes. The regulated enhancers were associated with enrichment for H3K4me1 and H3K27ac histone marks, showed regulated activities that matched activating histone marks and contained Hnf4a and other enriched motifs in male-biased, GH-repressed enhancer sets. Further, the impact of TCPOBOP exposure for 1 day or 2 weeks on HDI-STARR-seq activity was evaluated in mice of both sexes at 1,834 accessible chromatin regions. Induced H3K27ac and static H3K4me1 were enriched at TCPOBOP-responsive enhancers, as were DR4 motifs bound by CAR/RXR heterodimers. Motifs bound by Tcf, involved in cell proliferation, were enriched in HDI-STARR-seq active enhancers only after 2-week TCPOBOP exposure, indicating activation of a late responding signaling pathway. This research gives novel insights into the relationship between functional enhancer activity in mouse liver and hormonal and xenobiotic regulated epigenetic landscapes, and establishes the utility of HDI-STARR-seq for discovery of biologically relevant enhancer sequences in vivo. / 2026-09-18T00:00:00Z
145

Externe Stabilisierung von Venenbypässen durch Fibrinkleber führt zur Intimahyperplasie und aneurysmatischen Venengraftdegeneration. / Extravascular perivenous fibrin support leads to aneurysmal degeneration and intimal hyperplasia in arterialized vein grafts in the rat.

El-Sayed Ahmad, Ali 03 July 2012 (has links)
EINLEITUNG: Die externe Stabilisierung von Venengrafts soll die Scherkräfte auf die Venenwand vermindern und dadurch die Ausbildung einer Neointimaproliferation reduzieren. In experimentellen Modellen wurde diese Hypothese im Kurzzeitversuch überprüft. Es fanden sich in diesem Zeitraum widersprüchliche Ergebnisse. Ziel unserer Untersuchung war es, in einem neuen Modell der arterialisierten segmentalen Vena-jugularis-Transposition auf die infrarenale Aorta den Einfluss einer externen Fibrinkleberstabilisierung auf die Neointimabildung des Venengrafts im Langzeitversuch darzustellen. MATERIAL UND METHODEN: Männlichen Wistar-Ratten wurden Segmente der Vena jugularis entnommen und in Flussrichtung, nach Entfernen eines Aortensegmentes, in die infrarenale Aorta eingebracht. Somit entspricht dieses einem Venenbypassmodell mit komplett arterialisiertem Venengraft. Vor
146

Ultra-sonografia convencional e com Doppler colorido no diagnóstico de estenose da veia porta e da veia hepática em crianças submetidas a transplante hepático segmentar / Portal and Hepatic venous stenoses after pediatric segmental liver transplantation: the role of real time and Doppler ultrasound

Suzuki, Lisa 10 May 2006 (has links)
INTRODUÇÃO: Nos pacientes pediátricos, em razão das limitações relacionadas ao tamanho dos receptores, são utilizados segmentos do fígado provenientes de \"cadáver\" ou de doador vivo (\"fígado reduzido\"). As complicações decorrentes das anastomoses cirúrgicas podem ser de natureza vascular e biliar, sendo que a maior causa de perda do enxerto deve-se à trombose ou estenose da artéria hepática, veia porta e veias hepáticas. A ultra-sonografia convencional e com Doppler colorido (US-DC) pode ser utilizada para avaliação dessas complicações. Todavia, apesar da alta sensibilidade e especificidade deste método, há poucas descrições a respeito de parâmetros que podem ser utilizados para o estudo das alterações vasculares. OBJETIVO: Estabelecer parâmetros de ultra-sonografia convencional e com Doppler colorido (US-DC) para o diagnóstico de estenose da VP e VH no transplante hepático reduzido em crianças. MÉTODO: Estudo retrospectivo de 134 US-DC realizado em 48 crianças submetidas a transplante hepático segmentar no Instituto da Criança do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (ICr-HC-FMUSP), entre janeiro de 2002 e julho de 2005. No estudo da VP, os seguintes parâmetros foram analisados: calibre da VP na anastomose; velocidade máxima na anastomose (VP1); velocidade máxima no segmento pré-anastomose (VP2) e relação entre as velocidades máximas na anastomose/préanastomose (VP1/VP2). No estudo da VH, foram analisados: velocidade máxima na anastomose (VH1); velocidade na VH (VH2) e relação entre as velocidades máximas na anastomose/VH (VH1/VH2). Pacientes com estenose confirmada pela angiografia foram incluídos no grupo estenose e pacientes com angiografia ou cirurgia normal ou com boa evolução clínica foram incluídos grupo controle. RESULTADOS: Quatorze US-DC tiveram estenose da VP confirmadas pela portografia. O calibre da VP na anastomose foi menor no grupo estenose do que no grupo controle (média 2,5mm e 6,3mm respectivamente); PV1 e PV1/PV2 foram maiores no grupo estenose do que no grupo controle (média PV1 = 172cm/s, PV1/PV2 = 5,1 / PV1 = 83cm/s, PV1/PV2 = 1,8 respectivamente). O calibre da VP < 3,3mm apresentou a melhor correlação com a portografia (sensibilidade = 93% e especificidade = 88%), seguidos de VP1 > 128cm/s (sensibilidade = 86% e especificidade = 84%) e VP1/VP2 > 2,4 (sensibilidade = 79% e especificidade = 86%). Doze US-DC tiveram estenose da VH confirmada pela angiografia. A VH1 e HV1/VH2 foram maiores no grupo estenose do que no grupo controle (média VH1 = 202.2cm/s, VH1/VH2 = 6,0 / VH1 = 136,8cm/s, VH1/VH2 = 3,0 respectivamente). A relação VH1/VH2 > 4 apresentou a melhor correlação com a angiografia (sensibilidade = 83% e especificidade = 84%) seguido de VH1 > 128cm/s (sensibilidade = 83% e especificidade = 52%). CONCLUSÃO: Calibre da VP < 3,3mm na anastomose e relação das velocidades VH1/VH2 > 4 são altamente sensíveis e específicos no diagnóstico das estenoses da anastomose da VP e VH respectivamente, no póstransplante hepático em crianças / INTRODUCTION: Cadáveric split liver and living donor liver transplantation is mostly performed in children because of a shortage of suitable hepatic allograft in this population. Real time and Doppler ultrasound (CD-US) is the initial imaging modality for detection and follow-up of early and delayed vascular and non-vascular complications after liver transplant, but there are only few studies concerning its value in the diagnosis of venous complications. OBJECTIVE: Determine real time and Doppler ultrasound (CD-US) diagnostic parameters of portal (PV) and hepatic vein (HV) stenoses after segmental liver transplantation in children and assess their sensitivity and specificity. METHOD: Retrospective study of 134 CD-US performed in 48 patients submitted to segmental liver transplantation at Child Institute of University of Sao Paulo Medical School from January 2002 through July 2005. PV parameters: diameter at the anastomosis, velocities at the anastomosis (PV1) and at the pre-anastomosis segments (PV2) and the ratio PV1/PV2. HV parameters: velocities at the HV anastomosis to the inferior vena cava (HV1), at HV (HV2) and the ratio HV1/HV2. Stenosis group: patients with stenosis confirmed by angiography. Control group: patients presenting normal angiography or uneventhfull surgery or good clinical outcome. RESULTS: Fourteen CD-US had PV stenosis confirmed by portography. Diameter of PV at the anastomosis: narrower in the stenosis group (2.5mm) than in the control group (6.3mm) (p<.5). Mean PV1 and PV1/PV2: higher in the stenosis group than in the control group (PV1 = 172 cm/s, PV1/PV2 = 5.1/PV1 = 83cm/s, PV1/PV2 = 1.8). Statistical analysis determined as predictive of PV stenosis: PV diameter < 3.3mm (sensitivity of 93% and specificity of 88.4%); PV1 > 128cm/s (sensitivity of 86% and specificity of 84%) and PV1/PV2 > 2.4 (sensitivity of 79% and specificity of 86%). Twelve CD-US had HV stenosis confirmed by angiography. Mean HV1 and HV1/HV2: higher in the study group (HV1 = 202.2cm/s, HV1/HV2 = 6.0 / HV1 = 136.8cm/s, HV1/HV2 = 3.0) (p<.05). Statistical analysis determined as predictive of HV stenosis: PV1 > 128cm/s (sensitivity of 83% and specificity of 52%) and HV1/HV2 > 4 (sensitivity of 83% and specificity of 84%). CONCLUSION: PV diameter < 3.3mm at the anastomosis and HV1/HV2 > 4.0 are highly predictive for detection of PV and HV stenosis respectively, after pediatric segmental liver transplantation
147

Développement d’un modèle expérimental porcin d’autorétroperfusion myocardique à coeur battant : évaluation des réponses hémodynamiques et cardiaques avant et après occlusion de l’artère interventriculaire antérieure : potentialités d’applications cliniques / Development of a porcine beating-heart model of self-myocardial retroperfusion : evaluation of hemodynamic and cardiac responses to ischemia and clinical applications

Grandmougin, Daniel 01 June 2018 (has links)
Partie I : Objectifs. Ce travail propose une étude anatomique du coeur de porc afin d’élaborer des recommandations pour la réalisation d’une chirurgie cardiaque expérimentale. Matériels et méthodes. 16 porcs ont été étudiés. Le réseau coronaire artériel a été étudié chirurgicalement (n=13) et angiographiquement (n=10). Le réseau veineux coronaire a été analysé par dissections anatomiques (n=13) et injections rétrogrades de bleu de méthylène via le sinus coronaire (n=8). Résultats. Le positionnement intrapéricardique spécifique du coeur de porc, limite l’accès à l’aorte ascendante et à l’oreillette droite et nécessite des précautions particulières pour la réalisation d’une sternotomie et d’une canulation de l’aorte ascendante avec cardioplégie antérograde par la racine de l’aorte. Le réseau coronaire artériel est comparable au réseau humain (réseau droit dominant: 70%). Le sinus coronaire reçoit 4 afférences contre 3 chez l’homme. L’étude de la distribution de surface du réseau veineux nécessite la ligature préalable de la veine azygos gauche et confirme une asymétrie de perfusion au détriment du VD. La paroi antérieure du VD étant drainée par des petites veines cardiaques indépendantes du sinus coronaire. Conclusions. La connaissance des spécificités anatomiques cardiaques du porc a permis d’établir des recommandations pour la réalisation du modèle d’autorétroperfusion myocardique et plus largement de procédures chirurgicales cardiaques expérimentales sécurisées. Partie II : Objectifs. La perfusion rétrograde dans le sinus coronaire est utilisée pour la diffusion d’une solution de cardioplégie. Nous avons développé un modèle porcin d’autorétroperfusion myocardique à coeur battant (SMR) utilisant le réseau veineux coronaire pour assurer l’oxygénation du myocarde ventriculaire gauche. Ce modèle nous a permis d’évaluer les réponses hémodynamiques et cardiaques induites par SMR avant et après occlusion de l’artère IVA. Matériels et Méthodes. Une dérivation entre l’aorte ascendante et le sinus coronaire a été mise en place pour assurer une perfusion rétrograde sélective de la grande veine coronaire en sang oxygéné (SMR). Un groupe Contrôle (n=6) a permis de collecter des données physiologiques de référence et un groupe SMR (n=6) a été spécifiquement dédié à l’évaluation du concept d’autorétroperfusion myocardique après occlusion de l’artère IVA pendant au moins 240 minutes. Le débit cardiaque (CO), la pression maximale intra-VG (Pmax in-LV), le volume éjecté (SV), la fraction d’éjection ventriculaire gauche (FEVG), la durée diastolique (DD), la fréquence cardiaque (HR) et la pression artérielle systémique ont été monitorés en continu durant la période d’autorétroperfusion au moyen d’un cathéter de conductance type Millar® avant et après occlusion de l’IVA. La qualité de la perfusion systémique périphérique a été évaluée par l’analyse de la microcirculation sublinguale. En fin de procédure, les coeurs étaient prélevés pour une analyse histologique. Résultats. L’évaluation échographique de la FEVG était biaisée par la sternotomie alors que celle réalisée par le cathéter de conductance ne l’était pas. Le débit cardiaque après sternotomie a chuté en moyenne de 7.51% (P < 0.05). L’autorétroperfusion avec artère IVA perméable a généré des effets inotropes positifs, caractérisés par une augmentation du CO, du SV, de la Pmax in-LV et de la FEVG (P <0.0001). Après occlusion de l’IVA, l’autorétroperfusion a assuré, durant 240 minutes, une oxygénation myocardique et une compensation hémodynamique garantissant la préservation de la perfusion périphérique. L’analyse histologique a confirmé l’absence d’infarctus myocardique. Conclusions. L’autorétroperfusion myocardique a confirmé des propriétés inotropes positives et protectrices contre l’ischémie ouvrant des perspectives d’applications intéressantes / Part I: Objectives. This work reports an anatomic study of swine heart in order to produce technical recommendations and achieve successful experimental cardiac surgical procedures. Methods. 16 swines were studied. Coronary artery vessels were surgically (n=13) and angiographically (n=10) assessed. Coronary venous vessels were studied by anatomic dissections (n=13) and retrograde injection of methylene blue through the coronary sinus (n=8). Results. Specific pericardial positioning of swine heart dramatically differs from human heart resulting in a limited access to ascending aorta and right atrium, requiring surgical precautions to perform a safe sternotomy and canulation of ascending aorta with an antegrade cardioplegia. Arterial coronary pattern is similar to that of humans (right dominant supply: 70%). Pig coronary sinus receives 4 main branches vs 3 in human sinus. Preliminary ligation of the left azygos vein is required to visualize the surface distribution of methylene blue within the venous vessels, thereby confirming an optimized perfusion of the left ventricle whereas the right ventricle remains poorly perfused. This asymmetry of perfusion results from a specific venous drainage of the right ventricle through small cardiac veins disconnected from coronary sinus. Conclusions. Anatomic knowledge of swine heart validated surgical guidelines for designing the model of self-myocardial retroperfusion and safely performing experimental cardiac surgical procedures. Part II: Background. Retrograde perfusion into the coronary sinus is used to deliver cardioplegia. We developed an in-vivo porcine beating-heart model of self-myocardial retroperfusion (SMR) using the venous route to supply myocardial oxygenation and sought to assess hemodynamic and cardiac responses triggered by SMR before and after a prolonged occlusion of the LAD.Methods. A bypass-line between the ascending aorta and the coronary sinus was made to perform a selective retrograde perfusion of the great cardiac vein with oxygenated blood (SMR). A Control group (n=6) was assigned to collect baseline data, and an SMR group (n=6) was dedicated to undergo SMR with occlusion of LAD for 240 minutes. Cardiac output (CO), maximal pressure in the LV (Pmax in-LV), stroke volume (SV), left ventricular ejection fraction (LVEF), diastolic durations, heart rate, and arterial systemic pressure were evaluated with conductance catheters for the following periods: basal (before SMR), SMR with patent LAD, and SMR with occluded LAD. In order to assess peripheral perfusion, patterns of sublingual microcirculation were analyzed. At the end of the procedures, the hearts were harvested for histology. Results. Echographic LVEF evaluation was affected by sternotomy, but conductance catheter evaluation was not. Following pericardiotomy, CO decreased by 7.51% (P < 0.05). SMR with patent LAD showed inotropic properties with improvements in CO, SV, Pmax in-LV and LVEF (P < 0.0001). Following LAD occlusion, SMR supplied myocardial oxygenation with hemodynamic compensation and preserved the peripheral perfusion. Histology confirmed no signs of infarct. Conclusions. SMR showed capacities to produce inotropic effects and protect against ischemia, opening interesting potential applications
148

Prosthetic Vein Valve: Delivery and In Vitro Evaluation

Farrell, Laura-Lee Amelia Catherine 10 April 2007 (has links)
Venous disease will affect 1-3% of the western world at some point in their lives, yet there are few effective treatments for the venous system [1]. One such disease is chronic venous insufficiency (CVI), a painful and debilitating illness that affects the superficial and deep vein valves of the legs. When the valves become incompetent they allow reflux and subsequent pooling of blood. Current clinical therapies are only moderately; and therefore, the need for a better solution remains. Prosthetic venous valves were constructed from a novel hydrogel biomaterial patented by Georgia Tech. The valves had flexible cusps similar to normal, anatomic venous valves. The purpose of this work was to evaluate the thrombotic potential of the GT venous valve in an in vitro study and to design a percutaneous delivery system. In vitro thrombosis model provides an appropriate intermediate step between valve development and in vivo analysis, which is necessary to determine the biocompatibility of the prosthetic device. The flow system was modified from a one-pass, flow-through thrombosis assay using whole blood [2] to mimic pulsatile physiologic conditions. Cessation of flow indicated thrombotic obstruction. Histological analysis was performed using H and E staining and Carstairs stain (specific for platelets). A group of valves were lined with Dacron to confirm the thrombotic potential of the system. All Dacron valves were occluded by thrombus connecting the polymer fibers with adherent platelets. Whole blood perfused through the GT prosthetic valves exhibited no thrombosis or platelet adherence. All GT valves were patent and competent after blood perfusion. H and E staining revealed no thrombus deposition on the GT vein valves. A percutaneous delivery system was designed after evaluating the GT valves for their compressibility and plastic deformation over time. Appropriate stents, catheters and sheaths were selected. As designed, this system will be utilized in an ovine trial of the valve. Due to the low in vitro thrombotic potential and strong history of PVA as a medical implant material, positive trial results are expected. With successful animal and human trials this valve can provide a potential intervention for the 7 million people suffering from CVI.
149

Ultra-sonografia convencional e com Doppler colorido no diagnóstico de estenose da veia porta e da veia hepática em crianças submetidas a transplante hepático segmentar / Portal and Hepatic venous stenoses after pediatric segmental liver transplantation: the role of real time and Doppler ultrasound

Lisa Suzuki 10 May 2006 (has links)
INTRODUÇÃO: Nos pacientes pediátricos, em razão das limitações relacionadas ao tamanho dos receptores, são utilizados segmentos do fígado provenientes de \"cadáver\" ou de doador vivo (\"fígado reduzido\"). As complicações decorrentes das anastomoses cirúrgicas podem ser de natureza vascular e biliar, sendo que a maior causa de perda do enxerto deve-se à trombose ou estenose da artéria hepática, veia porta e veias hepáticas. A ultra-sonografia convencional e com Doppler colorido (US-DC) pode ser utilizada para avaliação dessas complicações. Todavia, apesar da alta sensibilidade e especificidade deste método, há poucas descrições a respeito de parâmetros que podem ser utilizados para o estudo das alterações vasculares. OBJETIVO: Estabelecer parâmetros de ultra-sonografia convencional e com Doppler colorido (US-DC) para o diagnóstico de estenose da VP e VH no transplante hepático reduzido em crianças. MÉTODO: Estudo retrospectivo de 134 US-DC realizado em 48 crianças submetidas a transplante hepático segmentar no Instituto da Criança do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (ICr-HC-FMUSP), entre janeiro de 2002 e julho de 2005. No estudo da VP, os seguintes parâmetros foram analisados: calibre da VP na anastomose; velocidade máxima na anastomose (VP1); velocidade máxima no segmento pré-anastomose (VP2) e relação entre as velocidades máximas na anastomose/préanastomose (VP1/VP2). No estudo da VH, foram analisados: velocidade máxima na anastomose (VH1); velocidade na VH (VH2) e relação entre as velocidades máximas na anastomose/VH (VH1/VH2). Pacientes com estenose confirmada pela angiografia foram incluídos no grupo estenose e pacientes com angiografia ou cirurgia normal ou com boa evolução clínica foram incluídos grupo controle. RESULTADOS: Quatorze US-DC tiveram estenose da VP confirmadas pela portografia. O calibre da VP na anastomose foi menor no grupo estenose do que no grupo controle (média 2,5mm e 6,3mm respectivamente); PV1 e PV1/PV2 foram maiores no grupo estenose do que no grupo controle (média PV1 = 172cm/s, PV1/PV2 = 5,1 / PV1 = 83cm/s, PV1/PV2 = 1,8 respectivamente). O calibre da VP < 3,3mm apresentou a melhor correlação com a portografia (sensibilidade = 93% e especificidade = 88%), seguidos de VP1 > 128cm/s (sensibilidade = 86% e especificidade = 84%) e VP1/VP2 > 2,4 (sensibilidade = 79% e especificidade = 86%). Doze US-DC tiveram estenose da VH confirmada pela angiografia. A VH1 e HV1/VH2 foram maiores no grupo estenose do que no grupo controle (média VH1 = 202.2cm/s, VH1/VH2 = 6,0 / VH1 = 136,8cm/s, VH1/VH2 = 3,0 respectivamente). A relação VH1/VH2 > 4 apresentou a melhor correlação com a angiografia (sensibilidade = 83% e especificidade = 84%) seguido de VH1 > 128cm/s (sensibilidade = 83% e especificidade = 52%). CONCLUSÃO: Calibre da VP < 3,3mm na anastomose e relação das velocidades VH1/VH2 > 4 são altamente sensíveis e específicos no diagnóstico das estenoses da anastomose da VP e VH respectivamente, no póstransplante hepático em crianças / INTRODUCTION: Cadáveric split liver and living donor liver transplantation is mostly performed in children because of a shortage of suitable hepatic allograft in this population. Real time and Doppler ultrasound (CD-US) is the initial imaging modality for detection and follow-up of early and delayed vascular and non-vascular complications after liver transplant, but there are only few studies concerning its value in the diagnosis of venous complications. OBJECTIVE: Determine real time and Doppler ultrasound (CD-US) diagnostic parameters of portal (PV) and hepatic vein (HV) stenoses after segmental liver transplantation in children and assess their sensitivity and specificity. METHOD: Retrospective study of 134 CD-US performed in 48 patients submitted to segmental liver transplantation at Child Institute of University of Sao Paulo Medical School from January 2002 through July 2005. PV parameters: diameter at the anastomosis, velocities at the anastomosis (PV1) and at the pre-anastomosis segments (PV2) and the ratio PV1/PV2. HV parameters: velocities at the HV anastomosis to the inferior vena cava (HV1), at HV (HV2) and the ratio HV1/HV2. Stenosis group: patients with stenosis confirmed by angiography. Control group: patients presenting normal angiography or uneventhfull surgery or good clinical outcome. RESULTS: Fourteen CD-US had PV stenosis confirmed by portography. Diameter of PV at the anastomosis: narrower in the stenosis group (2.5mm) than in the control group (6.3mm) (p<.5). Mean PV1 and PV1/PV2: higher in the stenosis group than in the control group (PV1 = 172 cm/s, PV1/PV2 = 5.1/PV1 = 83cm/s, PV1/PV2 = 1.8). Statistical analysis determined as predictive of PV stenosis: PV diameter < 3.3mm (sensitivity of 93% and specificity of 88.4%); PV1 > 128cm/s (sensitivity of 86% and specificity of 84%) and PV1/PV2 > 2.4 (sensitivity of 79% and specificity of 86%). Twelve CD-US had HV stenosis confirmed by angiography. Mean HV1 and HV1/HV2: higher in the study group (HV1 = 202.2cm/s, HV1/HV2 = 6.0 / HV1 = 136.8cm/s, HV1/HV2 = 3.0) (p<.05). Statistical analysis determined as predictive of HV stenosis: PV1 > 128cm/s (sensitivity of 83% and specificity of 52%) and HV1/HV2 > 4 (sensitivity of 83% and specificity of 84%). CONCLUSION: PV diameter < 3.3mm at the anastomosis and HV1/HV2 > 4.0 are highly predictive for detection of PV and HV stenosis respectively, after pediatric segmental liver transplantation
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Epidémiologie en soins primaires de la thrombose veineuse superficielle des membres inférieurs / Epidemiology of superficial-vein thrombosis of the legs in primary care

Frappé, Paul 14 October 2015 (has links)
La sévérité potentielle de la thrombose veineuse superficielle (TVS) des membres inférieurs a récemment été documentée par des études réalisées en soins secondaires et tertiaires. Son épidémiologie reste cependant inconnue en soins primaires. Le premier objectif de ce travail était de mesurer la prévalence de la TVS en soins primaires, ainsi que le taux d'évènements thromboemboliques concomitants au moment du diagnostic. Pour y répondre, un réseau de recherche collaborative entre médecins généralistes et médecins vasculaires de la région stéphanoise a été mis en place. Une étude transversale descriptive a été réalisée au sein de ce réseau pendant un an. La prévalence annuelle de la TVS a été mesurée à 0,64 pour mille habitants. Au moment du diagnostic, 24,6% des TVS étaient associées à une thrombose veineuse profonde symptomatique et 4,7% à une embolie pulmonaire symptomatique. Une seconde étude a recherché une variation saisonnière de la fréquence de la TVS en analysant les données individuelles de trois études aux designs différents ; l'étude STENOX, l'étude POST et l'étude STEPH. Une variation significative n'a été retrouvée que dans l'étude POST, et les peak-to-low ratios étaient inférieurs à 1,2 dans les trois études. Ainsi, si une variation existe, celle-ci parait être de faible envergure, sans conséquence sur la pratique et la recherche / The potential severity of superficial vein thrombosis (SVT) of the lower limbs has recently been shown by studies perfomed in secondary and tertiary care. The epidemiology of SVT remains unknown in primary care. The first objective of this study was to measure the prevalence of SVT in primary care, and the rate of concomitant thromboembolic events at diagnosis. A collaborative research network between general practitioners and vascular physicians from Saint-Etienne has been set up. A cross-sectional study has been conducted within this network during one year. The annual prevalence of SVT was measured to 0.64 per thousand inhabitants. At diagnosis, 24.6% of SVT were associated with symptomatic deep vein thrombosis and 4.7% with symptomatic pulmonary embolism. A second study was looking for a seasonal variation of SVT frequency by analyzing individual data from three studies with different designs; the STENOX study, the POST study and the STEPH study. A significant variation was found only in the POST study, and peak-to-low ratios were below 1.2 in the three studies. Thus, if other more powerful and exhaustive studies could find a seasonal variation, that variation would probably be of low magnitude and without clinical significance

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