Submitted by Franciele Moreira (francielemoreyra@gmail.com) on 2017-11-21T18:22:22Z No. of bitstreams: 2 Tese - Cyanéa Ferreira Lima Gebrim - 2017.pdf: 7795939 bytes, checksum: cb62a1c3e0f9541bf8bb295f89af4846 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-11-22T10:08:58Z (GMT) No. of bitstreams: 2 Tese - Cyanéa Ferreira Lima Gebrim - 2017.pdf: 7795939 bytes, checksum: cb62a1c3e0f9541bf8bb295f89af4846 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-11-22T10:08:58Z (GMT). No. of bitstreams: 2 Tese - Cyanéa Ferreira Lima Gebrim - 2017.pdf: 7795939 bytes, checksum: cb62a1c3e0f9541bf8bb295f89af4846 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-08-31 / AIM: to analyse the process of the implementation of nursing office for output follow-up of postoperative patientes of peripheral obstructive arterial disease, according to the structure, process and outcome indicators. METHOD: an uncontrolled, prospective intervention study conducted from 2013 to 2016 at the outpatient clinic of a university hospital in the Brazilian Midwest. Patients admitted to the nursing office for ambulatory follow-up in the postoperative period of peripheral obstructive arterial disease participated in the study. Two instruments were used to collect the data, the first to verify the sociodemographic profile and the second to measure the Patient Satisfaction index with the quality of nursing care. For statistical analysis, we used: absolute frequencies, median, mean and standard deviation, Raw Scale with logistic binary regression, Pearson correlation coefficient. RESULTS: the structure comprised: situational diagnosis, partnerships, training of the executing team and acquisition of physical and material resources. In the process, the methodology used for the care was the systematization of nursing care and as an outcome of the implementation of nursing office, the level of satisfaction of the patients with the nursing care was evaluated. A total of 39 patients, 51,3% male, mean age 63 years, 71.8% retired, 66.7% diabetic, 84.6% hypertensive, 71.8% dyslipidemic, 51.3% smoker, 84.9% sedentary. A total of 303 nursing consultations were performed, of which 80% of the patients evaluated were discharged and 15% needed rehospitalization. Nursing care reached an index of positivity (>80%) considered safe and of quality, and a high level of the patient satisfaction (mean: 4,195 and median 4). Five postoperative complications emerged: 53,9% surgical site infection, 10,3% amputations, 7,7% pain, 2,6% sepsis and 2,6% deaths. Statistically (p<0,05) more satisfied patients with nursing care were those that presented normal nutritional status (p=0,049), who assessed their health as poor or normal (p=0,020) and did not use anti-hypertensives (p=0,031). The Pearson Coefficients showed significant correlation, with an increasing association (r>0,0) between the technical-professional, educational and nurse's confidence domains. CONCLUSION: the structure of the nursing office, signaled important indicators in relation to the nursing practice, as a systematized service model for the follow-up of patients in the postoperative period of peripheral obstructive arterial disease, positively reflecting the improvement of the patients’ health. It emphasizes the early identification of some complications and the promotion of the quality of care with the lesion, in addition to narrowing the bond between the team and the patient. It impacted on the level of patient satisfation regarding the assistance provided by the nursing office team, in the outpatient follow-up of patients in the postoperative period of peripheral obstructive arterial disease. / OBJETIVO: analisar o processo de implantação do consultório de enfermagem para seguimento ambulatorial de pacientes em pós-operatório de doença arterial obstrutiva periférica, segundo os indicadores de estrutura, processo e resultado. MÉTODO: estudo de intervenção não controlado, prospectivo, realizado de 2013 a 2016, no ambulatório de um hospital universitário do Centro-Oeste brasileiro. Participaram do estudo pacientes admitidos no consultório de enfermagem para seguimento ambulatorial no pós-operatório de doença arterial obstrutiva periférica. Para a coleta dos dados, foram utilizados dois instrumentos, sendo o primeiro para verificar o perfil sociodemográfico, e o segundo para medir o índice de satisfação do paciente com a qualidade do cuidado de enfermagem. Para análise estatística, utilizaram-se frequências absolutas, mediana, média e desvio padrão, Raw Scale com regressão binária logística, coeficiente de correlação de Pearson. RESULTADOS: a estrutura compreendeu: diagnóstico situacional, parcerias, capacitação da equipe executora e aquisição de recursos físicos e materiais. No processo, a metodologia utilizada para o atendimento foi a sistematização da assistência de enfermagem, e como resultado da implantação do consultório, avaliou-se o nível de satisfação dos pacientes com os cuidados de enfermagem. Participaram 39 pacientes, 51,3% do sexo masculino, com média de idade de 63 anos, 71,8% aposentados, 66,7% diabéticos, 84,6% hipertensos, 71,8% dislipidêmicos, 51,3% tabagistas, 84,9% sedentários. Foram realizadas 303 consultas de enfermagem, das quais 80% dos pacientes avaliados receberam alta, e 15% necessitaram de reinternação. O cuidado de enfermagem alcançou índice de positividade (>80%) considerado seguro e de qualidade e alto nível de satisfação dos pacientes (média: 4,195 e mediana 4). Em meio às complicações pós-operatórias identificadas emergiram cinco: 53,9% infecções do sítio cirúrgico, 10,3% amputações, 7,7% dores, 2,6% sepses e 2,6% óbitos. Os pacientes estatisticamente (p<0,05) mais satisfeitos com os cuidados de enfermagem foram os que apresentaram estado nutricional normal (p=0,049), que autoavaliaram sua saúde como ruim ou regular (p=0,020) e que não faziam uso de anti-hipertensivos (p=0,031). Os Coeficientes de Pearson mostraram correlação significativa com associação crescente (r>0,0) entre os domínios Técnico-profissional, Educacional e Confiança do enfermeiro. CONCLUSÃO: a estruturação do consultório de enfermagem sinalizou indicadores importantes em relação ao consultório de enfermagem, como modelo de serviço sistematizado para o seguimento dos pacientes em pós-operatório de doença arterial obstrutiva periférica, refletindo positivamente na melhoria da saúde dos pacientes. Destacaram-se a identificação precoce de algumas complicações e a promoção da qualidade do cuidado com a lesão, além de estreitar o vínculo entre a equipe e o paciente. Impactou, no nível de satisfação dos pacientes em relação, a assistência prestada pela equipe do consultório de enfermagem, no seguimento ambulatorial de pacientes em pós-operatório de doença arterial obstrutiva periférica.

INTRODUÇÃO: Pré-condicionamento isquêmico remoto (PCIR) é o fenômeno pelo qual curtos períodos de isquemia sub-letal sobre um órgão ou tecido, intercalados com reperfusão do mesmo, conferem a outros órgãos ou tecidos distantes deste, um aumento na capacidade da resistir a episódios subsequentes de isquemia, a qual os mesmos possam ser expostos. Com base nesse fato, testamos a hipótese de que o pré-condicionamento isquêmico remoto em pacientes portadores de claudicação intermitente de membros inferiores poderia aumentar a capacidade de deambulação desses pacientes, extrapolando o conceito do PCIR de aumento da capacidade de preservação da integridade celular frente à isquemia, para a manutenção da função celular, tornando a célula mais apta ao trabalho em situações de privação de oxigênio, geradas pela restrição do fluxo sanguíneo, como ocorre nos pacientes com claudicação intermitente de membros inferiores, durante o exercício. OBJETIVOS: Avaliar se o PCIR aumenta a distância de início de claudicação e/ou a distância total de claudicação em pacientes com doença arterial obstrutiva periférica. MÉTODOS: Foram estudados 52 pacientes ambulatoriais que apresentavam queixa de claudicação intermitente dos membros inferiores, associada a um pulso arterial ausente ou reduzido no membro sintomático e/ou um índice tornozelo-braço <0,90. Estes pacientes foram randomizados em três grupos (A, B e C). Todos os pacientes foram submetidos a dois testes de caminhada em esteira de acordo com o protocolo de Gardner. O grupo A fez o primeiro teste de esteira sem o pré-condicionamento isquêmico remoto e, após 7 dias, foi submetido a um novo teste de esteira, agora precedido pelo pré-condicionamento isquêmico remoto. O grupo B foi submetido ao pré-condicionamento isquêmico remoto antes do primeiro teste de esteira e, após 7 dias, realizou novo teste de esteira, agora sem o pré-condicionamento isquêmico remoto. Já no Grupo C (grupo controle), ambos os testes de esteira foram realizados sem pré-condicionamento isquêmico remoto, também com 7 dias de intervalo. RESULTADOS: Os grupos A e C mostraram um aumento na distância de início de claudicação, no segundo teste, em comparação com o primeiro teste. O grupo A teve um aumento estatisticamente significativo, em relação ao grupo C (grupo controle). Com relação à distância total de claudicação, todos os grupos (A, B e C), mostraram um aumento estatisticamente significativo a favor do segundo teste, porém não foi observada diferença entre os grupos (A, B e C). CONCLUSÕES: O pré-condicionamento isquêmico remoto aumentou a distância inicial de claudicação em pacientes com claudicação intermitente, no entanto, ele não afetou a distância total de claudicação dos pacientes portadores de claudicação intermitente de membros inferiores / INTRODUCTION: Remote ischemic preconditioning (RIPC) is a phenomenon in which a short period of sub-lethal ischemia in one organ protects against subsequent bouts of ischemia in another organ. Extrapolating the RIPC concept of increasing the preservation of cell integrity capability against ischemia, for the maintenance of cellular function, making the cell more able to work in oxygen deprivation generated by the restriction of blood flow, as occurs in patients with intermittent claudication of the lower limbs during exercise, we hypothesized that RIPC in patients with intermittent claudication would increase muscle tissue resistance to ischemia, thereby resulting in an increased ability to walk. OBJECTIVES: To test this hypothesis, we performed gait tests in patients with claudication with and without prior RIPC and then compared the initial claudication distance (ICD) and the total walking distance (TWD). METHODS: In a claudication clinic, 52 ambulatory patients who presented with complaints of intermittent claudication in the lower limbs associated with an absent or reduced arterial pulse in the symptomatic limb and/or an ankle-brachial index < 0.90 were recruited for this study. The patients were randomly divided into three groups (A, B and C). All of the patients underwent two tests on a treadmill according to the Gardener protocol. Group A was tested first without RIPC. Group A was subjected to RIPC prior to the second treadmill test. Group B was subjected to RIPC prior to the first treadmill test and then was subjected to a treadmill test without RIPC. In Group C (control group), both treadmill tests were performed without RIPC. The first and second tests were conducted seven days apart. Brazilian Clinical Trials: RBR-7TF6TM. RESULTS: Group A and C showed an increase in the initial claudication distance in the second test compared to the first test. Group A had a statistically significant increase, compared with C group (control group). With respect to total claudication distance, all the groups (A, B and C) showed a statistically significant increase in favor of the second test, but there was no difference between groups (A, B and C). CONCLUSIONS: RIPC increased the initial claudication distance in patients with intermittent claudication; however, RIPC did not affect the total walking distance of the patients

INTRODUÇÃO: A Doença Arterial Periférica dos membros inferiores (DAP) é um acometimento relacionado à obstrução arterial desses membros, causada pela doença aterosclerótica, uma doença sistêmica. Por essa razão, a DAP costuma associar-se ao aumento da espessura íntima-média (EIM) carotídea e ao prejuízo cognitivo. No entanto, não se sabe qual o papel da EIM no prejuízo cognitivo observado na DAP. OBJETIVOS: Avaliar as funções cognitivas de pacientes com DAP, associá-las ao grau de prejuízo da circulação periférica e avaliar o papel da EIM nessa associação. CASUÍSTICA E MÉTODO: Foram selecionados 26 pacientes com DAP (68,57+8,34 anos; 65,4% do sexo masculino) e 40 indivíduos-controle (67,17+8,24 anos; 62,5% do sexo masculino). Todos participantes foram submetidos a uma avaliação sócio-demográfica, que coletou dados de caracterização do indivíduo e antecedentes clínicos; a uma investigação clínica, composta pela avaliação do índice tornozelo-braquial (ITB), pela medida da espessura íntima-média (EIM) carotídea, e pelo teste de caminhada de seis minutos (TC6\'); e a uma avaliação neuropsicológica, que consistiu nos seguintes instrumentos: Vocabulário (WAIS-III), Cubos (WAIS-III), Dígitos (WAIS-III), Wisconsin Card Sorting Test (WCST), Stroop Color Word Test (SCWT), FAS (COWAT), Animais (COWAT), Teste do Desenho do Relógio e Mini-Mental State Examination (MMSE). RESULTADOS: O grupo DAP apresentou pior desempenho na memória verbal tardia, na amplitude da atenção, na memória operacional, na atenção, no grau de abstração, na flexibilidade mental, na velocidade de processamento da informação, no controle inibitório/impulsividade, no vocabulário, na fluência verbal fonêmica, na fluência verbal semântica, na praxia construtiva e na função cognitiva global em relação ao grupo controle. Após ajuste para escolaridade, nível sócio-econômico, QI e sintomas psiquiátricos, o desempenho do grupo DAP se manteve pior na flexibilidade mental e na fluência verbal fonêmica. O grau de prejuízo da circulação periférica, avaliado pelo ITB, apresentou associação com a memória visual tardia, com a memória operacional, com a atenção, com o grau de abstração, com a velocidade de processamento da informação, com o controle inibitório/impulsividade, com o vocabulário, com a fluência verbal fonêmica e com a função cognitiva global. Após ajuste para escolaridade, nível sócio-econômico, QI e sintomas psiquiátricos, o ITB manteve associação com a fluência verbal fonêmica. Após ajuste para EIM, o ITB manteve associação com o vocabulário. CONCLUSÃO: O grupo de pacientes com DAP apresentou desempenho cognitivo prejudicado, quando comparado ao grupo controle, independente de escolaridade, nível sócio-econômico, QI e sintomas psiquiátricos. O grau de prejuízo da circulação periférica associou-se ao desempenho cognitivo, mas a EIM carotídea pareceu exercer um papel importante nessa associação / BACKGROUND: Peripheral arterial disease of the lower limbs (PAD) is related to arterial obstruction of these limbs, caused by atherosclerosis, a systemic disease. Therefore, PAD is usually associated with increased carotid intima-media thickness (IMT) and cognitive impairment. However, the role of IMT in cognitive impairment observed in PAD is unknown. OBJECTIVES: To evaluate the cognitive functions of patients with PAD, to associate them with the degree of impairment of peripheral circulation and to evaluate the role of IMT in this association. METHODS: 26 patients with PAD (68.57+8.34 years, 65.4% male) and 40 control subjects (67.17+8.24 years, 62.5 % male) were selected. All participants underwent a socio-demographic assessment, which collected data on individual\'s characteristics and medical history; a clinical investigation, consisting of the evaluation of the ankle-brachial index (ABI), the measurement of carotid intima-media thickness (IMT) and the six-minute walk test (6MWT); and a neuropsychological evaluation, which consisted of the following instruments: Vocabulary (WAIS - III), Block Design (WAIS - III), Digit Span (WAIS - III), Wisconsin Card Sorting Test (WCST), Stroop Color Word Test (SCWT) , FAS (COWAT) Animals (COWAT) , Clock Drawing Test and Mini - Mental State Examination (MMSE). RESULTS: The PAD group scored worse on delayed verbal memory, attention span, working memory, attention, degree of abstraction, mental flexibility, information processing speed, inhibitory control/impulsivity, vocabulary, phonemic verbal fluency, semantic verbal fluency, constructive praxis and global cognitive function compared to the control group. After adjustment for education, socioeconomic status, IQ and psychiatric symptoms, the performance of the PAD group remained worse in mental flexibility and phonemic verbal fluency. The degree of impairment of peripheral circulation, assessed by ABI, was associated with delayed visual memory, with working memory, with attention, with degree of abstraction, with information processing speed, with the inhibitory control/impulsivity, with vocabulary, with phonemic verbal fluency, and with global cognitive function. After adjustment for education, socioeconomic status, IQ and psychiatric symptoms, ABI remained associated with phonemic verbal fluency. After adjustment for IMT, ABI remained associated with the vocabulary. CONCLUSION: The group of patients with PAD showed impaired cognitive performance, when compared to the control group, regardless of education, socioeconomic status, IQ and psychiatric symptoms. The degree of impairment of peripheral circulation was associated with cognitive performance, but carotid IMT appeared to play an important role in this association

Background: Despite the fact that peripheral arterial disease (PAD) significantly increases the risk of cardiovascular mortality, it is significantly underdiagnosed and underrated. The purpose of this study was to evaluate the practice at a northeast Tennessee university primary care clinic regarding the diagnosis and treatment of PAD. Methods: A retrospective medical record survey was conducted to evaluate practice patterns in diagnosing and treating PAD in a university primary care clinic. A clinic population of 711 patients was selected using International Classification of Diseases-9 codes for coronary artery disease (CAD), cerebovascular disease (CVD), and/ or PAD. A sample of 180 patients (25.3%) was randomly selected using a systematic statistical method. Of these, 125 patients met the diagnostic criteria for CAD, CVD, and/or PAD. The study covered a 3-year period, from July 2001 until June 2004. Demographic and other data, including the use of antiplatelet therapy, were collected. Results: One hundred ten patients met all of the inclusion and exclusion criteria. Thirty-nine percent were males, and 61% were females. Overall, 79% had CAD, 53% had CVD, and 25% had PAD. Almost half of the patients had some combination of these. Only about 2% had PAD only compared with 36% with CAD only and 17% with CVD only. Although the prevalence of CAD and CVD (among other atherosclerotic vascular diseases) in our clinic was comparable to national figures, the prevalence of PAD was significantly lower (p = .004). The overall use of any antiplatelet agent was 84.2% for patients with only CAD and 80% for only CVD. There was not an adequate number of patients with only PAD to evaluate the use of antiplatelet therapy in this group. Conclusion: The low prevalence of PAD only (most PAD patients had coexisting CAD and CVD) indicates that PAD is underdiagnosed at our clinic. There was suboptimal use of aspirin and other antiplatelet drugs among patients with atherosclerotic vascular disease.

Purpose: To evaluate the use of the GoBack-catheter (Upstream Peripheral Technologies) in complex revascularizations in lower limb arteries. Materials and Methods: In this retrospective single-center study, the results of the first 100 consecutive patients including 101 limb-revascularizations, performed between May 2018 and July 2020 with the study device, were analyzed. In all cases, guidewire-crossing failed, and all lesions were chronic total occlusions (CTO), either de novo, reocclusions, or in-stent reocclusions. Successful crossing was defined as passing the CTO using the study device. Patency at discharge and after 30 days was defined as less than 50% restenosis on duplex sonography, without target lesion revascularization. Results: Median lesion length was 24 cm and 38 patients (37.6%) had a calcium grading according to the peripheral arterial calcium scoring system (PACSS) of 4 or 5. In 20.8% of patients, an occluded stent was treated. CTOs involved the femoropopliteal segment in 91.1%, iliac arteries in 5.9%, and tibial arteries in 7.9%. The GoBackcatheter was employed for entering into or crossing through parts or the full length of a CTO or an occluded stent as well as for re-entering into the true lumen after subintimal crossing. The device was used via contralateral and ipsilateral antegrade as well as retrograde access with an overall technical success rate of 92.1%. In 3 patients minor bleeding occurred at the crossing or re-entry site, which were managed conservatively. Thirty-day adverse limb events comprised minor amputations in 4 patients (4.0%), 1 major amputation (1.0%), and reocclusions in 7 limbs (6.9%). Conclusion: The new GoBack-catheter offers versatile endovascular applicability for complex CTO recanalization in a broad range of peripheral vascular interventions with a high technical success and low complication rate.

Vascular disease is the leading cause of death and disability worldwide. Incidence, risk factors, and outcome of coronary artery disease have been extensively studied, but there are fewer data on other forms of arterial disease, including carotid, aortic, visceral, and peripheral arterial disease. Although the burden of these diseases may be increasing due to the ageing population, we lack the most basic epidemiological data on which to base clinical decisions on individual patients (short and long-term prognosis); local service provision (current incidence and projected future burden); public health / screening initiatives (age and sex-specific incidence, risk factors, and outcome); and with which to assess current levels of primary prevention (pre-morbid risk factor control). Indeed, it is this lack of data, rather than a lack of treatments that is the greatest barrier to effective prevention. I have contributed to, cleaned, and analysed data from the Oxford Vascular Study, a prospective, population-based study (n=92,728) of all acute vascular events (2002-2012), and the Oxford Plaque Study, a carotid atherosclerosis biobank of over 1000 carotid plaques, in order to study these conditions. For acute aortic disease, I aimed to assess the risk factors associated with acute abdominal aortic aneurysms (AAA) and the population impact of the current UK AAA screening programme; and the incidence, risk factors, outcome, and projected future burden of acute aortic dissection. For acute peripheral arterial disease, I assessed the risk factors associated with premature onset and poor outcome, together with current levels of primary prevention. For symptomatic carotid artery disease, I studied the timing and benefits of surgical intervention in the current era; and went on to assess whether underlying carotid plaque morphology can be used to improve stroke risk stratification and help explain why ocular and cerebral stroke types have vast differences in future ipsilateral stroke risk. I found that compared with the current UK AAA screening strategy (one-off scan for men aged 65), screening of male smokers at 65 and all men at 75 would prevent nearly four-times as many deaths and three-times as many life-years lost with 21% fewer annual scans. I have also shown that incidence of acute aortic dissection is higher than previous estimates, a third of cases are out-of-hospital deaths, and uncontrolled hypertension is the most significant treatable risk factor for this condition. For acute peripheral arterial disease, the presence of multiple atherosclerotic risk factors are associated with premature onset, and severity of ischaemia, pre-morbid renal dysfunction, cardiac failure, and diabetes mellitus are predictive of future limb loss and survival. A significant proportion of acute peripheral events are AF-related in high risk patients who were not pre-morbidly anticoagulated despite having no contraindications and being at low risk of bleeding. Symptomatic carotid artery disease currently accounts for <10% of incident cerebrovascular events, and only 40% of these patients undergo surgical intervention. Due to improvements in medical therapy and on-going delays to intervention, little benefit is currently obtained from intervening in patients with <70% stenosis. Ipsilateral stroke risk is correlated with several carotid plaque features in a time-dependent manner, confirming the potential utility of plaque morphology in risk stratification. In addition, plaques from patients with cerebral events were significantly more unstable and inflammatory than from those with ocular events, helping explain differences in stroke risk between these groups. My findings advance the understanding of these conditions that form the backbone of modern vascular surgical practice, and I hope will improve prevention, clinical management, and outcome for patients with vascular disease.

Résumé : Bien que l’hypoxie soit un puissant inducteur de l’angiogenèse, l’activation des facteurs de croissance est perturbée en hyperglycémie au niveau du pied et du cœur. Cette perturbation entraîne la perte de prolifération et de migration chez les cellules endothéliales, musculaires lisses vasculaires et péricytes empêchant la formation de nouveaux vaisseaux qui mènera à l’amputation des membres inférieurs chez les patients diabétiques. Une étude a démontré qu’une augmentation de la protéine tyrosine phosphatase Src homology-2 domain-containing phosphatase-1 (SHP-1) en condition hyperglycémique chez les péricytes entraînait l’inhibition de la signalisation du PDGF-BB, ce qui résultait en le développement d’une rétinopathie diabétique. Nous avons alors soulevé l’hypothèse que l’expression de SHP-1 dans les cellules musculaires lisses vasculaires affecte la prolifération et la migration cellulaire par l’inhibition de la signalisation de l’insuline et du PDGF-BB en condition diabétique. Nos expérimentations ont été effectuées principalement à l’aide d’une culture primaire de cellules musculaires lisses primaires provenant d’aortes bovines. Comparativement aux concentrations normales de glucose (NG : 5,6 mM), l’exposition à des concentrations élevées de glucose (HG : 25 mM) pendant 48 h a résulté en l’inhibition de la prolifération cellulaire par l’insuline et le PDGF-BB autant en normoxie (20% O2) qu’en hypoxie (24 dernières heures à 1% O2). Lors des essais de migration cellulaire, aucun effet de l’insuline n’a été observé alors que la migration par le PDGF-BB fut inhibée en HG autant en normoxie qu’en hypoxie. L’exposition en HG à mener à l’inhibition de la signalisation de la voie PI3K/Akt de l’insuline et du PDGF-BB en hypoxie. Aucune variation de l’expression de SHP-1 n’a été observée mais son activité phosphatase en hypoxie était fortement inhibée en NG contrairement en HG où on observait une augmentation de cette activité. Finalement, une association a été constatée entre SHP-1 et la sous-unité bêta du récepteur au PDGF. En conclusion, nous avons démontré que l’augmentation de l’activité phosphatase de SHP-1 en hypoxie cause l’inhibition des voies de l’insuline et du PDGF-BB réduisant les processus angiogéniques des cellules musculaires lisses vasculaires dans la maladie des artères périphériques. / Abstract : Even though hypoxia is a strong angiogenic inducer, pro-angiogenic factor signaling pathways in peripheral limb and heart are altered by hyperglycemia. This disruption leads to loss of endothelial cells, vascular smooth muscle cells and pericytes proliferation and migration preventing new blood vessel formation which results in amputation of lower extremities in diabetic patients. A study has shown that increase expression of the protein tyrosine phosphatase Src homology-2 domain-containing phosphatase-1 (SHP-1) in hyperglycemic condition in pericytes caused PDGF-BB signaling inhibition resulting in the development of diabetic retinopathy. Our hypothesis is that SHP-1 expression in vascular smooth muscle cells inhibits cell proliferation and migration induced by insulin and PDGF-BB in diabetic condition. Our experiments were performed using primary culture of vascular smooth muscle cells (SMC) from bovine aortas. As compared to normal glucose concentrations (NG:5,6 mM), high glucose level (HG: 25 mM) exposure for 48h inhibited SMC proliferation induced by insulin and PDGF-BB in both normoxia (20% O2) or hypoxia (1% O2 for the last 24h). During cell migration assays, no effect of insulin was observed while PDGF-BB action of SMC migration was reduced in HG in both normal and low oxygen concentrations. HG exposure lead to inhibition of insulin- and PDGF-BB-stimulated PI3K/Akt signaling pathway in hypoxia. No variation of SHP-1 expression was observed in HG condition. However, SHP-1 phosphatase activity was elevated in HG condition during hypoxia as compared to NG concentrations. Finally, our data showed an association between SHP-1 and the PDGF receptor beta subunit. In conclusion, our results demonstrated that the increase of SHP-1 phosphatase activity in hyperglycemia and hypoxia environment caused inhibition of insulin and PDGF-BB signaling pathways reducing angiogenic processes in vascular smooth muscle cells contributing to peripheral arterial disease in diabetes.

La maladie des artères périphériques (MAP) se manifeste par une réduction (sténose) de la lumière de l’artère des membres inférieurs. Elle est causée par l’athérosclérose, une accumulation de cellules spumeuses, de graisse, de calcium et de débris cellulaires dans la paroi artérielle, généralement dans les bifurcations et les ramifications. Par ailleurs, la MAP peut être causée par d`autres facteurs associés comme l’inflammation, une malformation anatomique et dans de rares cas, au niveau des artères iliaques et fémorales, par la dysplasie fibromusculaire. L’imagerie ultrasonore est le premier moyen de diagnostic de la MAP. La littérature clinique rapporte qu’au niveau de l’artère fémorale, l’écho-Doppler montre une sensibilité de 80 à 98 % et une spécificité de 89 à 99 % à détecter une sténose supérieure à 50 %. Cependant, l’écho-Doppler ne permet pas une cartographie de l’ensemble des artères des membres inférieurs. D’autre part, la reconstruction 3D à partir des images échographiques 2D des artères atteintes de la MAP est fortement opérateur dépendant à cause de la grande variabilité des mesures pendant l’examen par les cliniciens. Pour planifier une intervention chirurgicale, les cliniciens utilisent la tomodensitométrie (CTA), l’angiographie par résonance magnétique (MRA) et l’angiographie par soustraction numérique (DSA). Il est vrai que ces modalités sont très performantes. La CTA montre une grande précision dans la détection et l’évaluation des sténoses supérieures à 50 % avec une sensibilité de 92 à 97 % et une spécificité entre 93 et 97 %. Par contre, elle est ionisante (rayon x) et invasive à cause du produit de contraste, qui peut causer des néphropathies. La MRA avec injection de contraste (CE MRA) est maintenant la plus utilisée. Elle offre une sensibilité de 92 à 99.5 % et une spécificité entre 64 et 99 %. Cependant, elle sous-estime les sténoses et peut aussi causer une néphropathie dans de rares cas. De plus les patients avec stents, implants métalliques ou bien claustrophobes sont exclus de ce type d`examen. La DSA est très performante mais s`avère invasive et ionisante. Aujourd’hui, l’imagerie ultrasonore (3D US) s’est généralisée surtout en obstétrique et échocardiographie. En angiographie il est possible de calculer le volume de la plaque grâce à l’imagerie ultrasonore 3D, ce qui permet un suivi de l’évolution de la plaque athéromateuse au niveau des vaisseaux. L’imagerie intravasculaire ultrasonore (IVUS) est une technique qui mesure ce volume. Cependant, elle est invasive, dispendieuse et risquée. Des études in vivo ont montré qu’avec l’imagerie 3D-US on est capable de quantifier la plaque au niveau de la carotide et de caractériser la géométrie 3D de l'anastomose dans les artères périphériques. Par contre, ces systèmes ne fonctionnent que sur de courtes distances. Par conséquent, ils ne sont pas adaptés pour l’examen de l’artère fémorale, à cause de sa longueur et de sa forme tortueuse. L’intérêt pour la robotique médicale date des années 70. Depuis, plusieurs robots médicaux ont été proposés pour la chirurgie, la thérapie et le diagnostic. Dans le cas du diagnostic artériel, seuls deux prototypes sont proposés, mais non commercialisés. Hippocrate est le premier robot de type maitre/esclave conçu pour des examens des petits segments d’artères (carotide). Il est composé d’un bras à 6 degrés de liberté (ddl) suspendu au-dessus du patient sur un socle rigide. À partir de ce prototype, un contrôleur automatisant les déplacements du robot par rétroaction des images échographiques a été conçu et testé sur des fantômes. Le deuxième est le robot de la Colombie Britannique conçu pour les examens à distance de la carotide. Le mouvement de la sonde est asservi par rétroaction des images US. Les travaux publiés avec les deux robots se limitent à la carotide. Afin d’examiner un long segment d’artère, un système robotique US a été conçu dans notre laboratoire. Le système possède deux modes de fonctionnement, le mode teach/replay (voir annexe 3) et le mode commande libre par l’utilisateur. Dans ce dernier mode, l’utilisateur peut implémenter des programmes personnalisés comme ceux utilisés dans ce projet afin de contrôler les mouvements du robot. Le but de ce projet est de démontrer les performances de ce système robotique dans des conditions proches au contexte clinique avec le mode commande libre par l’utilisateur. Deux objectifs étaient visés: (1) évaluer in vitro le suivi automatique et la reconstruction 3D en temps réel d’une artère en utilisant trois fantômes ayant des géométries réalistes. (2) évaluer in vivo la capacité de ce système d'imagerie robotique pour la cartographie 3D en temps réel d'une artère fémorale normale. Pour le premier objectif, la reconstruction 3D US a été comparée avec les fichiers CAD (computer-aided-design) des fantômes. De plus, pour le troisième fantôme, la reconstruction 3D US a été comparée avec sa reconstruction CTA, considéré comme examen de référence pour évaluer la MAP. Cinq chapitres composent ce mémoire. Dans le premier chapitre, la MAP sera expliquée, puis dans les deuxième et troisième chapitres, l’imagerie 3D ultrasonore et la robotique médicale seront développées. Le quatrième chapitre sera consacré à la présentation d’un article intitulé " A robotic ultrasound scanner for automatic vessel tracking and three-dimensional reconstruction of B-mode images" qui résume les résultats obtenus dans ce projet de maîtrise. Une discussion générale conclura ce mémoire. L’article intitulé " A 3D ultrasound imaging robotic system to detect and quantify lower limb arterial stenoses: in vivo feasibility " de Marie-Ange Janvier et al dans l’annexe 3, permettra également au lecteur de mieux comprendre notre système robotisé. Ma contribution dans cet article était l’acquisition des images mode B, la reconstruction 3D et l’analyse des résultats pour le patient sain. / Locating and quantifying stenosis length and severity are essential for planning adequate treatment of peripheral arterial disease (PAD). To do this, clinicians use imaging methods such as ultrasound (US), Magnetic Resonance Angiography (MRA) and Computed Tomography Angiography (CTA). However, US examination cannot provide maps of entire lower limb arteries in 3D, MRA is expensive and invasive, CTA is ionizing and also invasive. We propose a new 3D-US robotic system with B-mode images, which is non-ionizing, non-invasive, and is able to track and reconstruct in 3D the superficial femoral artery from the iliac down to the popliteal artery, in real time. In vitro, 3D-US reconstruction was evaluated for simple and complex geometries phantoms in comparison with their computer-aided-design (CAD) file in terms of lengths, cross sectional areas and stenosis severity. In addition, for the phantom with a complex geometry, an evaluation was realized using Hausdorff distance, cross-sectional area and stenosis severity in comparison with 3D reconstruction with CTA. A mean Hausdorff distance of 0.97± 0.46 mm was found for 3D-US compared to 3D-CTA vessel representations. In vitro investigation to evaluate stenosis severity when compared with the original phantom CAD file showed that 3D-US reconstruction, with 3%-6% error, is better than 3D-CTA reconstruction, with 4-13% error. The in vivo system’s feasibility to reconstruct a normal femoral artery segment of a volunteer was also investigated. All of these promising results show that our ultrasound robotic system is able to track automatically the vessel and reconstruct it in 3D as well as CTA. Clinically, our system will allow firstly to the radiologist to have 3D images readily interpretable and secondly, to avoid radiation and contrast agent for patients.

Made available in DSpace on 2016-01-26T12:51:33Z (GMT). No. of bitstreams: 1 luiscesarfavaspessoto_dissert.pdf: 660807 bytes, checksum: 232ed6cc6092dbaf2e4af68080b238f3 (MD5) Previous issue date: 2010-09-10 / One of the symptoms of peripheral artery disease (PAD) is erectile dysfunction (ED) which is characterized by a man s persistent inability to obtain and maintain a sufficient erection for satisfactory sexual intercourse. An elevation in the systemic arterial blood pressure is a common risk factor of both ED and PAD. Objective: The aim of this study was to study the influence of systemic arterial blood pressure on ED in patients with PAD. Patients and method: Fifty-two patients with ED with and without cardiovascular risk factors and with ages ranging from 42 to 78 years old (56.63 ± 10.34 years) were studied from January to June 2009. The ED was classified as mild, moderate and severe utilizing the International Index of Erectile Function. A physical examination was carried including measurement of the ankle-arm index (AAI), determined as the ratio between the highest systolic artery pressure (SAP) comparing ankles and the highest SAP between the brachial arteries. Statistical analysis was achieved by binary logistic regression, Pearson Chi-squared test, the log-likelihood ratio Chi-squared test for independent samples and the Kruskal-Wallis test. The level of significance was set for an alpha error of 5% (p-value < 0.05). Results: Of the studied patients, 11/52 (21.2%) had mild (Grade 1), 24 (46.1%) had moderate (Grade 2) and 17 had severe ED (Grade 3). The SAP in the brachial and anterior tibial arteries varied xi from 110 to 190 mmHg and from 90 to 180 mmHg, respectively. In respect to the AAI, 28 (53.8%) of the patients presented normal values or above 0.9 and 24 (46.2%) presented values of less than 0.9 thereby identifying PAD. Significant differences were identified on comparing the median degree of dysfunction of patients in different phases of PAD (p = 0.001) and between Grade 1 and Grade 3 (p = 0.0003) using the Kruskal-Wallis test with Bonferroni correction for multiple comparisons. Binary logistic regression showed that normotensive individuals in the initial phase of PAD with AAI between 0.8 and 0.9 presented with more severe ED when compared to hypertensive patients. Conclusions: An elevated systemic arterial pressure may have a protective effect against erectile dysfunction in the initial phases of peripheral arterial disease. / Um dos sintomas da doença arterial periférica (DAP) é a disfunção erétil (DE), que é caracterizada pela inabilidade persistente do homem em obter ou manter ereção suficiente para o intercurso sexual satisfatório. Tanto a DE como a DAP apresentam como fator de risco em comum a elevação da pressão arterial sistêmica. Objetivo: O objetivo desta pesquisa foi estudar a influência da pressão arterial sistêmica na DE em pacientes com DAP. Casuística e Método: Foram estudados 52 pacientes com DE com ou sem fator de risco cardiovascular, cuja idade variou de 42 a 78 anos (56,63 ± 10,34 anos) no período de janeiro a junho de 2009. A DE foi classificada em leve, moderada e grave utilizando o Índice Internacional de Função Erétil. Foi realizado exame físico geral direcionado por meio do índice tornozelo-braquial (ITB), determinado pela razão entre a mais elevada pressão arterial sistólica (PAS) do tornozelo e a mais elevada PAS entre as artérias braquiais. A análise de dados foi feita por meio de regressão logística binária, qui-quadrado de Pearson, quiquadrado da razão de verossimilhança para amostras independentes e Kruskal-Wallis, considerando erro alfa de 5%. Resultados: Dos pacientes estudados (n = 52), 11 (21,2%) tinham DE leve (grau 1), 24 (46,1%) moderada (grau 2) e 17 (32,7%) grave (grau 3). A PAS nas artérias braquial e tibial anterior variou de 110 a 190 mmHg e 90 a 180 mmHg, ix respectivamente. Com relação ao ITB, 28 (53,8%) dos pacientes apresentaram valores normais ou acima de 0,9 e 24 (46,2%) valores inferiores a 0,9, indicando a ocorrência de DAP. O resultado da comparação entre a mediana dos graus de DE de pacientes com diferentes fases de DAP por meio do teste de Kruskal-Wallis com correção de Bonferroni para comparações múltiplas das medianas mostrou diferenças significativas (p = 0,001) e entre os graus 1 e 3 (p = 0,0003). A regressão logística binária revelou que normotensos na fase inicial da DAP com ITB entre 0,8 e 0,9 apresentaram DE mais grave quando comparado com hipertensos. Conclusões: A pressão arterial sistêmica elevada pode ter efeito protetor contra a disfunção erétil nas fases iniciais da doença arterial periférica.

Lorsqu’un médecin diagnostique une pathologie chronique tel un diabète ou une artérite, pathologies choisies dans cette recherche, le patient entame, de fait, un processus d’apprentissage de la pathologie et de sa nouvelle vie avec ce diagnostic.Pourtant, ce processus diffère d’un patient à un autre et aboutit à des conduites diverses malgré des recommandations médicales consensuelles. Les professionnels de santé, en effet, ont des objectifs communs pour ces pathologies chroniques qui sont que les patients arrivent à avoir une alimentation équilibrée, pratiquent une activité physique quotidienne, s’abstiennent de tout comportement tabagique et prennent le traitement médicamenteux prescrit. Dans ce but, un certain nombre d’actions sont mises en place,de la campagne de santé publique au travail médical dans un cabinet libéral en passant par des programmes construits d’éducation. Ce que le patient fait grâce (ou malgré)cette éducation est l’objet de cette recherche.À la croisée des domaines de la santé et de l’éducation, nous avons choisi une méthodologie variée pour rendre compte à la fois de l’aspect anthropologique de cet apprentissage en considérant ce qui ne dépend pas du patient et à la fois de l’aspect didactique en observant le résultat des différentes situations sollicitées pour faire changer les patients. La première partie, centrée sur les aspects théoriques, montre la nécessité de considérer le corps dans l’éducation lorsqu’elle est dite thérapeutique.Pour comprendre ce qui est généralement peu ou pas interrogé par les acteurs de l’éducation thérapeutique, nous avons examiné l’ancrage historique des rapports entre le corps, la santé et l’éducation pour mieux étudier le « devenir malade » des patients considérés dans notre étude. Après un approfondissement historique du soin, de l’éducation puis du corps, les rapports actuels entre le corps et la santé ont été observés à l’aide des proverbes usuels, des livres en sciences humaines et sociales, de l’image publicitaire ainsi que des articles de presse. Les processus de transformation des corps malades pouvaient alors être compris selon cet ancrage et l’environnement éducatif dans lequel se situent actuellement les patients. Dans la troisième partie nous avons utilisé les récits des patients rencontrés. La mise en récit de la maladie est le dernier temps méthodologique. Grâce à l’histoire, à la compréhension du monde environnant les patients et à leur récit de vie, nous avons pu dégager des styles de discours. Trois grands styles sont repérés : celui des « experts » qui présentent une centration sur les savoirs,celui des « actifs » avec une centration sur l’activité physique et celui des « mangeurs »avec une centration sur l’alimentation. La compréhension de ces différents styles de discours est à mettre en lien avec les changements de conduites considérés sur le temps long de la pathologie chronique, dans le cadre de la dernière partie de ce travail. Ces modes de changements, tout au long du reste de la vie des patients, prennent différentes formes caractéristiques que nous avons pu dégager selon certains chemin explicatifs.L’ensemble des résultats permet de montrer l’intérêt d’interroger l’éducation thérapeutique actuelle et ses programmes ainsi que les concepts qui y sont attachés en utilisant le corps comme entrée. / As soon as a doctor diagnoses a chronic disease such as diabetes or arteritis, pathologies on which we shall focus in our research, patient begins a learning process of the pathology and their new life with this diagnosis. However this process differs from one patient to another and leads to diverse behaviours despite consistent medical recommendations. In fact, health professionals do seek common objectives: a balanced diet, daily physical activities, tobacco abstinence and a treatment medical that is followed. To reach this goal, various actions are put in place such as public health campaigns, work in the doctor’s office or Therapeutic Patient Education (TPE) programs. Our research focuses on how patients may react to (and benefit), from such education. At the junction of the health and education domains, we choose a diverse methodology to account for both the anthropological side of this learning experience, considering what does not depend on the patient, as well as its, the didactic side, thus observing the outcome of different pedagogical activities. The first part, focused on theory, demonstrates how considering the body is essential in education, especially in therapeutic education. To understand what is typically rarely considered, if not at all by TPE’s actors, we explore the historical roots of relationships between body, health and education to then better understand “becoming ill” as it relates to patients considered as part of our studies. After a historical investigation of cure, education and then the body, actual relationships between body and health are examined with using usual saying, books of Human and social sciences, advertisement pictures and newspaper articles. The transformation processes of sick bodies can then be understood from this viewpoint as well as through the patient’s educational environment. In the third part we used disease narratives from patients we have met. The disease storytelling within life stories is the last methodology step. In light of history, and through the patients’ environment and life stories, we could extract different speech styles that make sense when body speech is analysed in light of various anthropological data. Three major style types are identified: “experts” with centration on knowledge, “actives” with centration on physical activities and “eater” with centration on food. Understanding these style types requires considering behaviour changes in the long time of chronic pathologies, as done in the last part of our work. These different modes of change throughout the patients’ life present different characteristics, which we have been able to discern from various explanation paths. All results together allow us to demonstrate the value there is in questioning current TPE programs and its related concepts using the body as an input.