L'imagerie par résonance magnétique (IRM) est une technique d'imagerie médicale très riche et en plein essor. Elle permet d'obtenir de hautes résolutions temporelle et spatiale, et une très bonne caractérisation tissulaire. Malheureusement, les activités physiologiques de la circulation et de la respiration induisent des mouvements qui interfèrent avec le processus d'acquisition, assez lent, générant des artéfacts. D'un côté, l'exploration par IRM des organes thoraco-abdominaux en est perturbée, mais d'un autre côté c'est un outil non-invasif et précis d'analyse. Ainsi, nous avons montré que la course du diaphragme était de l'ordre de 1 à 2 cm dans une population de patients atteints de mucoviscidose, comme chez les sujets normaux, et légèrement plus importante en postérieur qu'en antérieur. Au cours d'une autre étude, nous avons observé que les déplacements crânio-caudaux du rein étaient aussi importants chez le nourrisson que chez l'adulte, avec des conséquences en imagerie fonctionnelle. Les méthodes gestion de ces mouvements, comme l'apnée ou la synchronisation sur des capteurs externes ou internes, restent cependant imparfaites. Nous montrons comment améliorer la qualité des images pulmonaires chez les patients atteints de mucoviscidose par une technique de double synchronisation cardiaque et respiratoire développée au laboratoire, et comment nous avons pu réaliser des séquences de ciné-cardiaque de haute qualité en respiration libre par utilisation de l'algorithme GRICS. Enfin, nous présentons plusieurs études portant sur l'analyse cinétique des traceurs, illustrant les contraintes particulières à cette situation, et posons les conditions d'un recalage efficient. / Magnetic Resonance Imaging (MRI) has become a major medical Imaging technique thanks to high temporal and spatial resolution, as well as to its abilities to distinguish between tissues. On one hand, MRI examinations of thoracic and abdomino-pelvic organs are compromised by the motions induced by circulation and respiration, but on the other hand, MRI is a non-invasive and precise tool to study these displacements. We have shown, in a group of patients with cystic fibrosis (CF), that the diaphragmatic course was around 1 to 2cm, as it is in normal subjects. In another study, we have found that motions of the kidney was in the same range in infants and in adults, despite the difference in the size of this organ; this is a major cause of error when performing functional analysis. Managing these motions is based upon breath holding and synchronization, both remaining imperfect. Thus, we showed how an in-lab dual synchronization, both cardiac and respiratory, improved quality of lung images in the patients with CF, and how we managed realizing high quality cardiac cine-MRI using the GRICS algorithm. At last, we discuss the specific difficulties of kinetic imaging of contrast agents through a few studies, and explain the bases of an efficient registration method.

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第21031号 / 社医博第85号 / 新制||社医||10(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 小池 薫, 教授 今中 雄一, 教授 湊谷 謙司 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

In Botswana, nurses play a major role in the provision of healthcare. Most of the time it is the professional nurses who frequently discover patients with cardiac arrests and it is necessary for them to be trained to perform CPR as efficiently as possible. The aim of this study is to describe and explore the perceptions, barriers and needs as experienced by nurses in Botswana during the provision of CPR. For this study, the researcher utilised both quantitative and qualitative research designs in four phases. Phase one assessed and audited the existing available facilities in the provision of CPR. Phase two investigated the existing knowledge and skills of registered nurses in the performance of CPR. Focus groups discussions and semi-structured interviews were held during phase three to identify the perceived barriers, needs in the performance of CPR. In phase four, the researcher made recommendation to improve the provision of CPR in relation to system, nurse and patient. Convenience sampling and purposive sampling were used in this study respectively. The auditing of the equipment in the two referral hospitals showed that the availability of equipment was below 50%. The CPR knowledge and skills demonstrated by the nurses in the pre-test were inadequate. Following CPR training with the help of a manikin, the knowledge and skills among registered nurses improved substantially. The focus group discussions and semi-structured interviews among registered nurses and senior nurse mangers revealed that there was a lack of organisational support and resources, lack of knowledge and skills among registered nurses, inadequate policies and protocols are the major contributory factors affecting the registered nurses performance in the provision of CPR. In order to enhance the performance of the registered nurses while providing CPR, the researcher recommends the two referral hospitals to • have adequate provision of equipment • introduce regular BLS training program for registered nurses • have clearly defined policies regarding the nurses’ role on end-of-life care / Health Studies

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Magister Scientiae (Nutrition Management) - MSc(NM) / Introduction: Non-communicable diseases (NCDs) are among the leading causes of premature death in South Africa. As is the case with many countries in transition, in South Africa the burden of pre-NCDs such as overweight and obesity is increasing. The aim of this mixed method study was to gain an understanding on the knowledge, attitudes, practices and perceptions and related factors of primary and secondary school teachers in Limpopo Province of South Africa regarding nutrition related non-communicable diseases (NR-NCDs). Methodology: A mixed method approach, parallel convergent study design was used to collect both qualitative and quantitative data from a group of randomly selected public school teachers in Rakwadu Circuit, Limpopo, with due consideration of the ethical issues involved. For the quantitative inquiry, a previously validated structured questionnaire was adapted to collect data from 114 teachers, while 2 Focus Group Discussions (FGDs) were conducted by the researcher to collect the qualitative data. Information collected included teachers‟ dietary practices, physical activity levels and their knowledge, attitudes and perceptions towards nutrition related non-communicable diseases. Each of these variables had a number of questions which were scored and a mean score for each participant was obtained. Anthropometric measurements collected included Body Mass Index (BMI) and waist circumference (WC).

There is accumulating evidence on differences in the link between types of dairy products and cardio-metabolic health, but inconsistent findings limit the field. In my PhD project, I undertook an epidemiological investigation comprising inter-related but distinct themes evaluating aspects of nutritional, molecular and genetic epidemiology to advance scientific understanding. I undertook research to describe dairy consumption patterns over time by evaluating nationally-representative data of the United Kingdom National Diet and Nutrition Survey. I observed significant time trends for specific dairy types and groups, which were different among different groups of people e.g. adults younger than 65 years or elderly people. Using data from the large Fenland (n~12,000) and EPIC Norfolk (n~25,000) studies, I investigated associations of total and types of dairy consumption with markers of metabolic risk and adiposity as potential pathways to cardio-metabolic disease. The analyses showed differential associations of dairy types and groups mainly with markers of adiposity and lipidaemia. I explored the potential of objective markers to assess dairy consumption, by examining metabolomics profiles and blood fatty acids to identify a set of biomarkers predicting dairy consumption and prospective associations of the identified biomarkers with type 2 diabetes risk. I was able to develop and validate metabolite scores reflecting consumption of some dairy products and observed inverse associations between some of these scores and type 2 diabetes incidence. I analysed genetic determinants of dairy consumption, using a genome-wide association study in the UK Biobank (n~500,000) and identified single nucleotide polymorphisms predicting milk, cheese and total dairy consumption. Overall, this PhD work contributed towards (1) a more precise description of dairy consumption patterns in the UK, (2) hypothesis formulation for potential biological pathways linking to cardio-metabolic disease, (3) discovery of metabolite scores as potential dairy biomarkers and (4) hypothesis formulation for potential genetic predictors of dairy consumption.

In Botswana, nurses play a major role in the provision of healthcare. Most of the time it is the professional nurses who frequently discover patients with cardiac arrests and it is necessary for them to be trained to perform CPR as efficiently as possible. The aim of this study is to describe and explore the perceptions, barriers and needs as experienced by nurses in Botswana during the provision of CPR. For this study, the researcher utilised both quantitative and qualitative research designs in four phases. Phase one assessed and audited the existing available facilities in the provision of CPR. Phase two investigated the existing knowledge and skills of registered nurses in the performance of CPR. Focus groups discussions and semi-structured interviews were held during phase three to identify the perceived barriers, needs in the performance of CPR. In phase four, the researcher made recommendation to improve the provision of CPR in relation to system, nurse and patient. Convenience sampling and purposive sampling were used in this study respectively. The auditing of the equipment in the two referral hospitals showed that the availability of equipment was below 50%. The CPR knowledge and skills demonstrated by the nurses in the pre-test were inadequate. Following CPR training with the help of a manikin, the knowledge and skills among registered nurses improved substantially. The focus group discussions and semi-structured interviews among registered nurses and senior nurse mangers revealed that there was a lack of organisational support and resources, lack of knowledge and skills among registered nurses, inadequate policies and protocols are the major contributory factors affecting the registered nurses performance in the provision of CPR. In order to enhance the performance of the registered nurses while providing CPR, the researcher recommends the two referral hospitals to • have adequate provision of equipment • introduce regular BLS training program for registered nurses • have clearly defined policies regarding the nurses’ role on end-of-life care / Health Studies

Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, 2006. / Submitted by Érika Rayanne Carvalho (carvalho.erika@ymail.com) on 2009-12-01T21:56:16Z No. of bitstreams: 1 2006_Jefferson Guimarães de Resende.pdf: 1101721 bytes, checksum: 6f61ae357943c934bb6e33885e572ec2 (MD5) / Approved for entry into archive by Daniel Ribeiro(daniel@bce.unb.br) on 2010-01-15T21:02:54Z (GMT) No. of bitstreams: 1 2006_Jefferson Guimarães de Resende.pdf: 1101721 bytes, checksum: 6f61ae357943c934bb6e33885e572ec2 (MD5) / Made available in DSpace on 2010-01-15T21:02:54Z (GMT). No. of bitstreams: 1 2006_Jefferson Guimarães de Resende.pdf: 1101721 bytes, checksum: 6f61ae357943c934bb6e33885e572ec2 (MD5) Previous issue date: 2006-12-15 / Introdução: considerando-se que a ventilação pulmonar mecânica manual pode ser realizada com diferentes tipos de equipamentos, resolvemos estudar o desempenho de médicos utilizando uma bolsa auto-inflável e o CFR, avaliando a mecânica ventilatória, a troca gasosa e a ocorrência de lesão pulmonar. Métodos: estudo experimental, de intervenção, randomizado, analítico. Quatorze médicos ventilaram dez carneiros recém-nascidos prematuros, durante 45 minutos em cada animal, totalizando cinco animais por equipamento. Os dados de mecânica ventilatória foram gravados e feitas as gasometrias arteriais seriadas. Resultados: não houve diferença estatisticamente significante (p=0,628) entre as médias dos pesos dos animais (2,784±0,84 e 2,544±0,35 gramas), mas houve diferença (p<0,05) para as médias da freqüência respiratória (49±17 e 36±12,7 ciclos por minuto), do pH (7,34±0,11 e 7,03±0,16), da soma das áreas alveolares (36.146.174,00 e 34.756.547,30 micrômetros) e da soma das áreas parenquimatosas (5.024.281,36 e 5.846.885,40 micrômetros), entre os ventilados com a bolsa auto-inflável e o CFR, respectivamente. Houve diferença estatisticamente significativa (p<0,05) entre as medianas do pico de pressão inspiratória [39,8 (IQ24-75% de 30,2-47,2) e 30,5 (IQ25-75% de 28,6-31,9) cmH2O], do volume corrente/kg [17,8 (IQ25-75% de 14,1-22,4) e 14,2 (IQ25-75% de 10,2-16,6) ml], da complacência dinâmica/kg [0,447 (IQ25-75% de 0,367-0,540) e 0,584 (IQ25-75% de 0,393-0,694) ml/cmH2O/kg], da pressão parcial de oxigênio no sangue arterial [203,2 (IQ25-75% de 147,3-256,4) e 53,7 (IQ25-75% de 46,2-170,5) mmHg] e da pressão parcial de gás carbônico no sangue arterial [27,6 (IQ25-75% de 20,5-38,9) e 77,4 (IQ25-75% de 50,8-101,7) mmHg], para a bolsa e o CFR, respectivamente. Conclusões: o pico de pressão e o volume corrente foram mais elevados utilizando a bolsa e a complacência dinâmica foi maior entre aqueles ventilados com o CFR. A bolsa produziu hiperoxemia e hipocapnia e lesões pulmonares mais intensas; o CFR promoveu normoxemia, mas com PaCO2 elevado. Palavras-chave: ressuscitação cardio-pulmonar, recém-nascido, asfixia neonatal, ventilação mecânica, volume de ventilação pulmonar. _____________________________________________________________________________________ ABSTRACT / Introduction: considering that manual pulmonary mechanical ventilation can be done using different devices, we attempted to compare the performances of medical doctors using the self-inflating bag, and the CFR, evaluating the ventilatory mechanics, the gases exchange, and the occurrence of pulmonary injury. Methods: experimental, interventional, randomized, and analytical study. Fourteen medical doctors ventilated a total of ten newborn premature lambs, from which five individuals were ventilated using a self-inflating bag, and five were ventilated using the CFR, for 45 minutes each. The ventilatory mechanics results were recorded and the arterial gas measurements in series were taken. Results: there were no statistically significant differences (p=0.628) in lambs mean weight between the self-inflating bag group and the CFR group (2.784±0.84 g, and 2.544±0.35 g, respectively). However, there were statistically significant differences (p<0.05) in the: (1) mean ventilatory frequency (49±17, and 36±12.7 cycles per minute); (2) the mean pH (7.34±0.11, and 7.03±0.16); (3) the sum of the alveolar areas (36,146,174.00 μm, and 34,756,547.30 μm), and (4) the sum of the parenquima areas (5,024,281.36 μm and 5,846,885.40 μm), between the selfinflating bag group and the CFR group, respectively. Furthermore, we found statistically significant differences (p<0.05) in the median of: (1) the peak inspiratory pressure [39.9 (IQ25-75% 30.2-47.2) cmH2O], and [30.5 (IQ25-75% 28.6-31.9) cmH2O]; (2) of the tidal volume/kg [17.8(IQ25-75% 14.1-22.4) ml], and [14.2 (IQ25-75% 10.2-16.6) ml]; (3) of the dynamic compliance/kg [0.447 (IQ25- 75% 0.367-0.540) ml/cmH2O], and [0.584 (IQ25-75% 0.393-0.694) ml/cmH2O]; (4) of the PaO2 [203.2 (IQ25-75% 147.3-256.4) mmHg], and [53.7 (IQ25-75% 46.2- 170.5) mmHg]; (5) and of the PaCO2 [27.6 (IQ25-75% 20.5-38.9) mmHg], and [77.4 (IQ25-75% 50.8-101.7) mmHg], between the self-inflating bag group and the CFR group, respectively. Conclusion: the peak inspiratory pressure and the tidal volume were higher using the self-inflating bag, while the dynamic compliance was higher using the CFR. The bag induced hyperoxia and hypocapnia and more intense pulmonary injuries. The CFR induced normoxia, but with higher PaCO2.

Au cours de ma thèse je me suis intéressé à deux aspects de l’immunité dans les pathologies pulmonaires chroniques : l’immunité innée et l’inflammation dans le développement de l’hypertension artérielle pulmonaire (HTAP) ; l’immunité adaptative et la réponse vaccinale antigrippale chez des patients atteint de la broncho-pneumopathie chronique obstructive (BPCO).Ma première étude a porté sur l’implication de la voie de signalisation IL-1ß/IL-1R1/MyD88 dans le développement de l’HTAP, l’IL-1ß étant une cytokine majeure de l’immunité innée. Nos résultats montrent que le remodelage vasculaire pulmonaire et l'inflammation dans l’HTAP dépendent de la voie de signalisation IL-1R1/MyD88. L’IL-1R1 et MyD88 sont tout deux nettement surexprimés dans les vaisseaux pulmonaires de patients atteints d’HTAP idiopathique. Chez les souris exposées à une hypoxie chronique de 21 jours, l’augmentation de la production d'IL-1ß et de l'expression de IL-1R1 et MyD88 précèdent le développement de l’HTAP. Les souris IL-1R1-/- et MyD88-/- étant protégées similairement contre le développement de l’HTAP, nous avons pu identifier IL-1R1 comme un acteur majeur dans la pathogenèse de l’HTAP, affectant à la fois la prolifération des cellules musculaires lisses d’artères pulmonaires (CML-AP) et le recrutement des macrophages. La protection partielle contre la maladie des souris M.lys-Cre MyD88fl/fl indique que les effets de l’IL-1ß/IL-1R1 sur l’HTAP sont médiés en partie par l'activation des macrophages. De plus, l’anakinra (IL-1Ra) permet de reverser partiellement l’HTAP établie, chez les souris SM22-5HTT+ et chez les rats exposés à la monocrotaline.Ma seconde étude a porté sur l’efficacité de la réponse vaccinale antigrippale chez des patients atteints de BPCO. Sur une cohorte de 15 sujets atteints de BPCO et 15 sujets sains, nos résultats montrent une altération de la réponse humorale et de la réponse cellulaire au vaccin antigrippale où l’on observe une production d’anticorps anti-hémagglutinine affaiblie et une diminution de la production d’IFNγ par les lymphocytes T auxiliaires (CD4+). L’analyse des sous-populations lymphocytaires indique qu’il existe chez ces patients un défaut de différentiation des cellules B, où l’on observe un taux de cellules B naïves (CD21+CD27-) plus important et un taux de cellules B mémoires (CD21+CD27+) switchées moindre (CD27+IgD-) que chez les patients contrôles, pouvant expliquer l’altération de la réponse vaccinale. Enfin, nous avons observé que les sous-populations lymphocytaires, en particulier les cellules B naïves et mémoires, sont corrélées avec deux paramètres cliniques de la maladie, la DLCO et le score d’emphysème.Ces travaux de thèse montrent donc que les interventions pharmacologiques ciblant la voie IL-1ß/IL-1R1 peuvent être prometteuses pour le traitement de l'HTAP et que de nouvelles stratégies vaccinales antigrippales doivent être développées pour les patients atteints de BPCO afin d’augmenter l’efficacité du vaccin et de prévenir les exacerbations. / During my thesis, I was interested in two aspects of immunity in chronic lung diseases: innate immunity and inflammation in the development of pulmonary arterial hypertension (PAH); adaptive immunity and influenza vaccine response in patients with chronic obstructive pulmonary disease (COPD).My first study was focused on the involvement of the IL-1ß/IL-1R1/MyD88 signaling pathway in the development of PAH; IL-1ß is a major cytokine in innate immunity. Our results show that the pulmonary vascular remodeling and inflammation in PAH depend on IL-1R1/MyD88 signaling pathway. IL-1R1 and MyD88 are both significantly overexpressed in pulmonary vessels of patients with idiopathic PAH. In mice exposed to chronic hypoxia during 21 days, the increase in production of IL-1ß and expression of IL-1R1 and MyD88 are involved in the development of PAH. Mice deleted with IL-1R1 and MyD88 were similarly protected against the development of PAH. We identified IL-1R1 as a major player in the pathogenesis of PAH, affecting both pulmonary arteries smooth muscle (PA-SMC) proliferation and recruitment of macrophages. The partial protection against the disease in mice M.lys-Cre MyD88fl/fl indicates that the effects of IL-1ß/IL-1R1 on PAH are mediated partially by activation of macrophages. In addition, anakinra (IL-1Ra) partially reverse established PAH in SM22-5HTT + mice and rats exposed to monocrotaline.My second study was focused on the efficacy of influenza vaccine response in patients with COPD. In a cohort of 15 subject with COPD and 15 healthy subjects, our results show that both the humoral and the cellular responses to influenza vaccination are impaired in patients with COPD, with a blunted antibody response and decreased INFγ production by helper T lymphocytes (CD4+). Analysis of lymphocyte subpopulations indicates an impairment of B cell differentiation in these patients: naive (CD21+ CD27-) B cell counts were higher and switched memory B-cell (CD27+ IgD-) counts were lower in COPD patients, which could explain the impairment of vaccine response. Interestingly, these changes in B cell subsets correlated with DLCO and the CT emphysema score.This thesis work thus shows that pharmacological interventions targeted towards IL-1ß/IL-1R1 may be promising for the treatment of PAH and new influenza vaccine strategies should be developed for COPD patients to increase vaccine efficacy and prevent exacerbations.

Cardiosurgery is a potent activator of the immune response similar to sepsis in critically ill patients. Therefore the differential diagnostics of infectious and non-infectious etiology plays an important role. The aim of the study was to compare the biomarkers in the diagnostics of patients after cardiosurgery and in septic patients. 24 patients fulfilling criteria of sepsis and 8 patients after cardio surgery were involved in the study. We demonstrated higher specificity and sensitivity of PCT in comparison with CRP at diagnostics of sepsis. sTREM-1, expression of TREM-1 on monocytes, TREM-1 on granulocytes and the number of FoxP3+T regulatory lymphocytes do not provide a reliable differential diagnostics of infectious and non-infectious etiology of examined group of the patients. The number of lymphocytes in patients with sepsis is a useful parameter at this diagnostics. Cardiosurgery represent a significant impulse for the evocation of the systemic inflammatory response of non-infectious etiology.