This investigation was concerned with measuring aspects of cardiac function in conscious control, diabetic, hypertensive control, and hypertensive diabetic rats. Preliminary studies were conducted to determine catheter suitability and acute responses to atropine and angiotensin II in conscious animals. The catheter-manometer was tested using a square wave impact and was shown to accurately reproduce a left ventricular pressure pulse. Intravenous atropine caused both heart rate and left ventricular +dP/dt to rise. Intravenously administered angiotensin II caused systolic blood pressure to increase dramatically. In this case heart rate fell and +dP/dt was elevated. Hypertension was induced with deoxycorticosterone acetate (DOCA) and saline drinking water. Rats were first made diabetic with streptozotocin (60 mg/kg; i.v.). One week following this, subcutaneous DOCA (25 mg/kg) was administered twice weekly and all animals received saline drinking water. Following 2 and 5 weeks of DOCA treatment rats were catheterized and resting cardiovascular function was measured. DOCA treatment caused increased systolic and diastolic blood pressures to occur in control and diabetic rats at 2 and 5 weeks. Bradycardia was also observed in DOCA-diabetic and DOCA-control rats at 2 and 5 weeks of treatment. Two and 5 week hypertensive diabetic and control rats exhibited elevated -dP/dt and +dP/dt. The rate of contraction was shown to be proportional to the magnitude of systolic blood pressure in all treatment groups. It is concluded that diabetic rats and control rats did not differ in their response to hypertension after 5 weeks of DOCA treatment. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

The morbidity of and the mortality from cardiac disease are higher in diabetic patients. Clinical and experimental evidence suggests that diabetes-induced changes at the level of myocardium can, at least partially, contribute to these cardiac problems. The mechanism(s) involved in this diabetic cardiomyopathy is still unclear, but one defect appears to occur in the alpha₁-adrenoceptor system. Altered myocardial sensitivity and responsiveness to alpha₁-adrenoceptor agonists have been reported in experimental diabetes mellitus. Stimulation of alpha₁-adrenoceptors is known to produce a positive inotropic effect and has been recently shown to stimulate the hydrolysis of phosphoinositides. To evaluate the possibility that the changes in the inotropic responsiveness to alpha₁-adrenoceptor stimulation in the diabetic heart could be linked to altered alpha₁-adrenoceptor-stimulated phosphoinositide turnover and further to the development of diabetic cardiomyopathy, we studied contractility and receptor-stimulated phosphoinositide turnover following norepinephrine (in the presence of propranolol) stimulation in right ventricles from male Wistar rats (200-225 g) which were made diabetic with streptozotocin (55 mg/kg, i.v.). Rats were sacrificed six weeks after the induction of diabetes. Diabetic rats were characterized by decreased body weight gain, hypoinsulinemia, hyperglycemia and hyperlipidemia. Stimulation of alpha₁-adrenoceptors by norepinephrine (in the presence of propranolol) in right ventricles resulted in the formation of inositol monophosphate (measured with a radioisotope method) and inositol 1,4,5-trisphosphate (measured with an inositol 1,4,5-trisphosphate protein binding assay kit) in a time- and concentration-dependent manner in both control and diabetic rats. The increase in inositol 1,4,5-trisphosphate levels preceded the increase in the alpha₁-adrenoceptor-mediated positive inotropic effect. Diabetic hearts showed a greater maximum inotropic response to norepinephrine stimulation and also had a higher inositol 1,4,5-trisphosphate levels. However, with the radioisotope method, a decreased inositol monophosphate formation was shown in diabetic hearts compared with controls. Omega-3 fatty acids supplementation (Promega[symbol omitted], 0.5 ml/kg/day) had no significant effect on the changes in norepinephrine-stimulated inositol monophosphate formation in diabetic hearts. In the presence of the cyclooxygenase inhibitor indomethacin or the thromboxane synthetase inhibitor imidazole, the norepinephrine-stimulated positive inotropic effect and inositol 1,4,5-trisphosphate formation were significantly increased in control hearts, but were unaltered in the hearts from diabetics. The addition of the prostacyclin synthetase inhibitor tranylcypromine reduced the norepinephrine-stimulated positive inotropic effect and inositol 1,4,5-trisphosphate formation only in diabetic hearts and had no effect in the controls. While inositol 1,4,5-trisphosphate may be able to mediate only transient inotropic effects produced by alpha₁-adrenoceptor stimulation, diacylglycerol may provoke a sustained positive inotropic effect by activating slow Ca²⁺ channels through stimulation of protein kinase C. Our results showed that the diabetic hearts had a higher protein kinase C activity in the membrane fraction compared with controls and this was accompanied by a decrease in cytosolic protein kinase C activity. The present study suggests that the increases in inositol 1,4,5-trisphosphate levels and the membrane fraction protein kinase C activity may be implicated in the increased inotropic responsiveness to alpha₁-adrenoceptor stimulation in the hearts of the streptozotocin-diabetic rats. The increases in inositol 1,4,5-trisphosphate level and protein kinase C activity could induce Ca²⁺ overload in the diabetic heart which might be involved in the development of diabetic cardiomyopathy. The results from the omega-3 fatty acid study indicate that the changes in cardiac alpha₁-adrenoceptor-mediated inositol phosphates formation cannot contribute to the previously described improved cardiac function of omega-3 fatty acid-treated streptozotocin-diabetic rats. The nature and physiological significance of the enhanced positive inotropic effect and inositol 1,4,5-trisphosphate formation in the control heart with the addition of indomethacin and imidazole is still unclear. The effect of tranylcypromine may indicate the participation of prostaglandins in mediating the enhanced alpha₁-inotropic effect of norepinephrine in the diabetic heart. / Pharmaceutical Sciences, Faculty of / Graduate

La prévalence du diabète de type 2 ne cesse d’augmenter et la tranche d’âge des plus de 65 ans subit la hausse la plus importante. Des différences liées au genre ont été rapportées entre les hommes et les femmes diabétiques de type 2, notamment en ce qui concerne les complications macrovasculaires du diabète mais il n’y a pas, à notre connaissance, d’étude française qui s’est spécialement intéressée à cette question. La majorité des études internationales ne se sont pas intéressées aux sujets âgés mais à toute la population diabétique et beaucoup d’entre elles sont anciennes, datant d’avant l’introduction des nouveaux traitements cardiovasculaires avec un fort niveau de preuve.Ce travail avait comme objectif d’évaluer l’existence de différences liées au genre dans la prise en charge du diabète de type 2 au sein d’une population contemporaine de sujets âgés pris en charge en conditions de vie réelle en soins primaires. Les objectifs spécifiques étaient de comparer l’équilibre du diabète et le contrôle des facteurs de risque cardiovasculaire et la survenue d’événements cliniques majeurs (décès ou événement cardiovasculaire majeur, hospitalisation) entre les hommes et les femmes, et d’évaluer le rôle du genre du médecin traitant dans ces différences potentielles.La cohorte S. AGES diabète de type 2 est une étude observationnelle prospective de sujets âgés de 65 ans ou plus, non institutionnalisés, ayant un diabète de type 2. Au total 983 patients ont été inclus entre avril 2009 et juin 2011 par 213 médecins. L’évolution clinique et la survenue d’événements majeurs ont été renseignées pendant 3 ans. Des modèles mixtes ont été utilisés dans les analyses statistiques en raison de la corrélation entre les mesures répétées du même patient et la corrélation entre les patients du même médecin.Pendant toute la période du suivi, l’équilibre du diabète de type 2, estimé par l’hémoglobine glyquée HbA1c, n’était pas différent entre les hommes et les femmes, le contrôle de la pression artérielle était meilleur chez les hommes que chez les femmes en analyse bivariée mais pas en analyse multivariée. Par contre, le contrôle du cholestérol LDL était meilleur chez les hommes que chez les femmes avec un risque relatif pour les femmes par rapport aux hommes d’avoir un LDL non contrôlé (>1 g/l) de 2,56 (IC à 95 % 1,82-3,59 ; p<0,001). Cette différence était présente dans le groupe traité par statines ainsi que dans le groupe non traité.En ce qui concerne la survenue d’événements cliniques majeurs, les femmes avaient un risque plus faible de développer un événement clinique majeur (décès toutes causes confondues, événement cardiovasculaire majeur) par rapport aux hommes avec un risque relatif de 0,60 (IC à 95 % 0,40-0,91 ; p= 0.016) ou d’être hospitalisées avec un risque relatif de 0,71 (IC à 95 % 0,52-0,96, p=0,029). La majorité des hospitalisations était liée aux pathologies concomitantes autres que le diabète, surtout chez les hommes qui étaient davantage admis en CHU/CHR que les femmes. Le risque de développer des complications microvasculaires du diabète n’est pas différent entre les hommes et les femmes.Enfin, nos analyses n’ont pas montré de différence entre les médecins hommes et les médecins femmes au niveau du contrôle des facteurs de risque cardiovasculaire, de la réalisation d’examens de surveillance, de dépistage des complications, ni de prescription de traitements antidiabétiques et cardiovasculaires.Nos résultats montrent que les différences liées au genre dans cette population de patients diabétiques âgés sont réservées à un cholestérol LDL plus élevé chez les femmes que chez les hommes, mais qui ne s’accompagne pas d’une augmentation du risque de survenue d’événements cliniques majeurs (qui reste plus élevé chez les hommes). Cependant il faut interpréter ces résultats dans le contexte de la cohorte S.AGES avec des biais de sélection au niveau médecin et au niveau patient ainsi qu’une sous-représentation des médecins femmes. / The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide and this trend is projected to persist because of the demographic shift and the obesity pandemic. The elderly represent more than half of subjects with T2DM and this proportion is expected to increase in the future. Cardiovascular disease is the main cause of morbidity and mortality in elderly subjects with T2DM. Moreover, although non-diabetic women have lower risk of developing cardiovascular diseases compared to non-diabetic men of the same age, this “female advantage” seems to diminish or disappear in the setting of T2DM. Indeed, compiled data suggest that type 2 diabetes affects the risk of cardiovascular disease differentially according to gender. To the best of our knowledge, there is no French study that had looked at this issue. The majority of international studies have not focused on the elderly group but on the whole diabetic population and many of them are conducted before the introduction of evidence-based cardiovascular treatments.The aim of the present work was to assess gender-related differences in the management of elderly patients with T2DM followed-up in the primary care. Specifically, we compared the control of T2DM and other cardiovascular risk factors between women and men, the occurrence of major clinical events (all-cause mortality and major vascular events as well as all-cause hospitalization) between women and men, and the influence of physician gender on the quality of care in subjects with T2DM.The S.AGES T2DM cohort is a prospective observational study whose objective was to describe the real-life medical management of subjects aged 65 years or more with T2DM. 983 non institutionalized subjects were included by 213 general practitioners from April 2009 through June 2011 and followed-up for 3 years. For data obtained during the follow-up period, multilevel mixed-effect regression models were used to account for repeated measurements (for each subject) and clustering (A cluster is a group of subjects followed-up by the same GP).Over the follow-up period, T2DM and blood pressure control were not different between the genders but LDL cholesterol was better controlled in men than in women. The odds ratio for women being associated with uncontrolled LDL cholesterol (>1 g/l) was 2.51 (95% CI 1.79–3.53, p<0.001). This gender-related difference in LDL cholesterol levels was independent of statin therapy.Concerning major clinical events, women were at lower risk than men to develop the composite endpoint (all-cause mortality and major vascular events) with a relative risk of 0.60 (95% CI 0.40-0.91, p=0.016) and the hospitalization endpoint (OR 0.71, 95% CI 0.52-0.96, p=0.029). Coexisting diseases were responsible to the majority of hospitalizations especially in men who were more likely to be admitted to a university hospital when compared to female counterparts. The risk of developing microvascular complications and hypoglycemia were not different between men and women.Finally, we didn’t find any significant difference between male and female physicians in terms of quality of care in subjects with T2DM (control of T2DM and other cardiovascular risk factors, tests to screen for diabetes complications, or the prescription of anti-diabetic and cardiovascular treatments).Our results show that gender differences in this population of elderly diabetics are restricted to higher LDL cholesterol in women than in men but this does not seem to increase the risk of major clinical events (which are higher in male subjects). However, these results should be interpreted with cautious because of selection biases at the physician and patient level as well as under-representation of female physicians.

This study sought to evaluate a new method that uses injection of fibrin sealant under simultaneous balloon occlusion for the treatment of postinterventional access site bleeding complications. With the rising complexity of interventional procedures, iatrogenic false aneurysms and active bleeding has become more common. In general, these complications are associated with increased morbidity and mortality, especially if surgical repair is required. Although high success rates are reported for ultrasound‐guided compression and ultrasound‐guided thrombin injection, these methods are not always feasible. All procedures of fibrin sealant injection under simultaneous balloon occlusion for the treatment of postinterventional access site bleeding complications or pseudoaneurysm were prospectively collected. Additional data were retrospectively obtained and analyzed for all patients treated by this new method. In total, 53 patients were included from 2018 to 2021. Most of the access site complications were related to transcatheter aortic valve replacement (40%) or percutaneous coronary intervention (21%), but also to a wide variety of other procedures. Of the 53 patients, 30 had to be treated for false aneurysms and 23 for active bleeding. A high primary success rate of 94% was achieved. Recurrences of false aneurysms occurred in six patients, of which only one needed open surgical repair. Regarding complications, two peripheral embolisms, thereof one requiring additional stent implantation occurred. Balloon‐assisted thrombin injection seems to be feasible and safe. It provides a new alternative to prevent surgery for patients where common techniques are unavailable or have failed.

Introduction: Vasectomy is considered a safe and effective contraceptive method with fewcomplications. Complications are most often hematomas, pain or infection. Previous studiessuggest that the surgeon’s experience level is associated with potential complications. Aim: To evaluate complications after vasectomy and to investigate if specific patientcharacteristics and/or surgical experience can predict complications related to vasectomysurgeries. Methods: Five hundred consecutive journals of vasectomy patients at the Department of Urologyin Örebro University Hospital during 2019 and 2020 were investigated. Patient characteristics andinformation about the surgery were collected. Comparison was made between patient groups toinvestigate if complications were more common in patients with diabetes, cardiovascular diseaseor previous surgery in the scrotal/groin area, as well as in patients operated on by one versus twosurgeons, and residents versus specialized surgeons. Results: No statistically significant association could be found between patient characteristics(diabetes, cardiovascular disease, previous surgery) and complications. Furthermore, the numberof operating surgeons and the surgeons’ experience levels did not have any statistically significantassociation to complication rates. Conclusion: No patient factors could be used to predict vasectomy outcome. Complication ratesare the same in patients operated by surgical residents and specialized surgeons.

Tableau d'honneur de la Faculté des études supérieures et postdoctorales, 2016-2017 / La sténose aortique est la cardiopathie valvulaire la plus fréquente retrouvée chez les patients agés. Suite à l’apparition des symptômes, la survie des patients diminue de façon drastique en l’absence d’un remplacement valvulaire aortique. Cependant, une proportion considérable de ces patients n’est pas opérée en raison d'un risque chirurgical élevé, l'âge étant l'une des principales raisons de refus d’un remplacement valvulaire aortique chirurgical. Ce défaut dans la prise en charge des ces patients a favorisé le développement du remplacement valvulaire aortique par cathéter où implantation valvulaire aortique par cathèter (TAVR ou TAVI), qui a représenté une révolution dans le traitement de la sténose aortique. Cette intervention est actuellement un traitement de routine chez les patients à haut risque chirurgical atteints d’une sténose aortique, même si la chirurgie cardiaque n’est pas contre-indiquée. Ces dernières années ont vu un changement de profil des candidats potentiels vers une population à plus faible risque. Cependant, plusieurs préoccupations demeurent. L’une des plus importantes est la survenue des arythmies et de troubles de conduction, notamment le bloc de branche gauche et le bloc auriculo-ventriculaire, qui sont des complications fréquemment associées au TAVR. Malgré l’évolution de la technologie et le développement de nouveaux dispositifs réduisant le taux global de complications, aucune amélioration n’a pas été intégrée pour prévenir l’apparition de telles complications. De plus, l'utilisation de certains dispositifs de nouvelle génération semble être associée à un risque accru de troubles de conduction, et par conséquent, l'incidence de ces complications pourrait augmenter dans le futur. Cependant, L'impact et l'évolution de ces complications sont inconnus. Ce travail de recherche évalue l'incidence et l'évolution des troubles de conduction suite au TAVR et l'impact des blocs de branche gauche de novo et de l'implantation d'un pacemaker sur les résultats cliniques et échocardiographiques. / The aortic stenosis is one of the most frequent valvular heart diseases, which is mostly diagnosed in older patients. With the symptoms onset, the lifespan of such patients dramatically decrease unless an aortic valve replacement is performed. However, a considerable proportion of such patients do not undergo cardiac surgery owing to a perceived high risk, being the advanced age one of main reasons to deny surgical aortic valve replacement. Such deficiency in the care of these patients has favoured the development of transcatheter aortic valve replacement or implantation (TAVR or TAVI), which has revolutionized the treatment of aortic stenosis. This treatment is now a routine therapy in high-risk patients with aortic stenosis, even if cardiac surgery is not contraindicated. Indeed, the last years have witnessed a shift in the use of this technology to lower risk populations. TAVR technology has experienced a dramatic evolution to integrate enhanced iterations which have allowed, along with the improvement of the technology, a reduction in the risk of complications associated with this therapy. However, several concerns remain. One of them is the occurrence of arrhythmias and conductions disturbances, in particular left bundle branch block and atrioventricular block, which are frequent complications of TAVR. Despite the evolution of the technology and development of new devices leading to a reduction in the overall rate of complications, no new iterations have been integrated to prevent the occurrence of such complications. Moreover, the use of new-generation devices seems to be associated with an increased risk of such complications, and therefore, its incidence is expected to increase in the next future. Nonetheless, little is known about the impact and evolution of these disorders. This thesis evaluates the incidence and evolution of new-onset arrhythmias and conduction abnormalities after TAVR and the impact of new-onset left bundle branch block and permanent pacemaker implantation on late clinical and echocardiographic outcomes.

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2015-2016 / Ce mémoire porte sur les propriétés fonctionnelles du plancher pelvien à la suite de traitements pour un cancer de l’endomètre. Chez les femmes, le cancer de l’endomètre est le cancer gynécologique ayant la plus forte prévalence. Les traitements oncologiques de ce cancer ont des conséquences néfastes sur la continence urinaire et il est possible que des altérations aux muscles du plancher pelvien à la suite de ces traitements puissent expliquer en partie cette problématique. Ce mémoire est composé de deux études principales. La première étude porte sur la recension des écrits liés aux impacts de la radiothérapie sur la structure anatomique et la fonction musculaire du plancher pelvien chez des adultes atteints d’un cancer pelvien. La deuxième étude compare les propriétés fonctionnelles du plancher pelvien de femmes avec incontinence urinaire à la suite d'un cancer de l'endomètre traité par chirurgie et une radiothérapie adjuvante (groupe à l’étude), à celles de femmes avec hystérectomie sans incontinence (groupe témoin). Cette étude a permis de mettre en évidence une diminution de l’ouverture maximale à l’entrée vaginale, de la longueur vaginale, de la force maximale volontaire du plancher pelvien, du taux de développement de la force dans un test de force maximale et de la coordination lors d’un test de contractions rapides. Ainsi, les deux études de ce mémoire apportent de nouvelles évidences sur les altérations des propriétés fonctionnelles du plancher pelvien à la suite de traitements pour un cancer génital. / This master’s thesis is on functional properties of the pelvic floor muscles after treatments for endometrial cancer. In women, endometrial cancer is the most prevalent gynecological cancer. Urogenital dysfunctions, such as urinary incontinence, are frequent after oncological treatments of this cancer, and it is possible that alterations of the pelvic floor muscles could explain, in parts, such dysfunction. This thesis is constituted of two main studies. The first study is on the systematic review of the literature regarding the documented effects of radiation therapy on the anatomical structure and physiological function of the pelvic floor muscles of adults with pelvic cancer. The second study concerns differences in pelvic floor functional properties of women experiencing urinary incontinence after surgical and radiotherapy treatments for endometrial cancer (study group) to women with hysterectomy for benign disease (comparison group). This study presented results of reduced maximal anterior-posterior opening of the vaginal entry, vaginal length, maximal voluntary contraction, maximal rate of force development in a strength test, and coordination in a speed’s test. These two studies altogether bring new evidence that there are alterations to pelvic floor functional properties following treatments for genital cancer.

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2007-2008. / OBJECTIF : L’étomidate, un agent inducteur très utilisé pour l’intubation des traumatisés cranio-cérébraux (TCC), soulève des débats par rapport à son effet néfaste sur la fonction surrénalienne. Cette étude visait à évaluer le risque et la durée de l’insuffisance surrénalienne relative (ISR) induite par l’étomidate chez les TCC. Secondairement, elle visait à évaluer son effet sur la mortalité et la morbidité. MÉTHODES : Cette étude d’observation a adopté un devis longitudinal prospectif. Les sujets admissibles étaient tous des TCC modérés et sévères intubés, âgés de 16 ans ou plus, qui ont été admis à l'Hôpital de l'Enfant-Jésus entre août 2003 et novembre 2004. Un test de stimulation à l’ACTH (250 mcg) a été effectué 24, 48 et 168 heures après l’intubation. L’ISR a été définie par une augmentation de la cortisolémie une heure après l’ACTH (delta cortisol) de moins de 248,4 nmol/l. Des analyses de régression logistique et linéaire ont été effectuées afin de mesurer la force de l'association entre l’usage de l'étomidate et le risque d'ISR, la mortalité et les mesures de morbidité. RÉSULTATS : Parmi les 94 sujets admissibles à l’étude, 40 ont subi des tests à l’ACTH. Parmi ces 40 sujets, 15 ont reçu l’étomidate et 25 ont reçu un autre agent inducteur. À 24 heures, il n’y avait pas d’augmentation d’ISR associée à l’étomidate. Par contre, l’étomidate était associé à un delta cortisol plus faible (moyenne ajustée : 305,1 nmol/l, IC 95 % [214,7-384,8] versus 500,5 nmol/l, IC 95 % [441,8-565,7]; p=0,02). À 48 et à 168 heures, cette différence disparaissait. Pour tous les patients admissibles (n=94), l’étomidate était associé à un risque non statistiquement significatif de mortalité plus élevé (RC ajusté : 4,8, IC 95 % [0,6-35,9]). Par contre, il était associé à une hausse significative du risque de pneumonie (RC ajusté : 3,0, IC 95 % [1,0-8,7]; p=0,04). La durée moyenne ajustée de séjour aux soins intensifs n’était pas différente (10,2 jours pour l’étomidate versus 10,8 jours pour les autres agents). Au congé, le score moteur ajusté de la mesure d’indépendance fonctionnelle (MIF) était plus bas pour les sujets exposés à l’étomidate (32 versus 56, p=0,002), mais le score cognitif ajusté n’était pas différent entre les groupes (35 versus 46, p=0,15). CONCLUSION : L’étomidate inhibe la production de cortisol suite à une stimulation à l’ACTH jusqu’à 24 heures après une dose unique utilisée pour intuber des TCC modérés et sévères. Son impact sur la mortalité et sur la morbidité reste à préciser à l’aide d’un essai clinique randomisé et contrôlé. / INTRODUCTION: Etomidate is one of the most frequently used anesthetic induction agents for intubating patients with traumatic brain injury (TBI), although the clinical impacts of its adverse effects on adrenal function are debated. Therefore, it is important to assess the consequences of any adrenal suppression that could result from its use in patients with TBI. OBJECTIVE: The primary objective of this study was to determine the risk and the length of relative adrenal insufficiency (RAI) induced by etomidate in patients intubated for moderate and severe TBI. The secondary objective was to determine etomidate’s impact on mortality and morbidity. METHODS: This was a prospective cohort study. Eligible participants were moderate to severe TBI victims aged 16 years and over, intubated and admitted to a tertiary neurosurgical reference center between August 2003 and November 2004. ACTH stimulation tests (250 mcg) were performed on participants 24, 48 and 168 hours after intubation. RAI was defined as an increased of serum cortisol one hour post ACTH (delta cortisol) of less than 248.4 nmol/L (9 mcg/dl). Logistic and linear regression models assessed the association between the exposure to etomidate and the risk of RAI. RESULTS: Of the 94 subjects eligible to participate, 40 underwent ACTH testing. Fifteen subjects received etomidate and 25 received other induction agents. At 24 hours, etomidate did not change the risk of RAI. However, etomidate decreased the delta cortisol (adjusted mean: 305.1 nmol/l, 95% CI [214.7-384.8] vs. 500.5 nmol/l, 95% CI [441.8-565.7], p=0.02). At 48 and 168 hours, this difference disappeared. For all eligible subjects (n=94), there was a non significant trend for increased mortality in the etomidate group (adjusted OR: 4.8, 95% CI [0.6-35.9]). Etomidate was however associated with a significant increased risk of pneumonia (adjusted OR: 3.0, 95% CI [1.0-8.7]; p=0.04). The adjusted length of stay in the intensive care unit was not different (10.2 days for etomidate versus 10.8 days for the other agents). At discharge, the adjusted motor Functional Independence Measure score was significantly lower for subjects in the etomidate group (32 versus 56, p=0.002), but the adjusted cognitive score was not significantly different (35 versus 46, p=0.15). CONCLUSION: Etomidate decreases the adrenal response to an ACTH test up to 24 hours after a single dose used for the intubation of TBI victims. A large randomized controlled trial is needed to further assess its impact on morbidity and mortality.

Le cycle régulier des contractions des oreillettes, suivi par des contractions ventriculaires, pompe le sang de manière efficace à travers le coeur. Par contre, lorsque le fin équilibre qui régule le mécanisme est débalancé, les arythmies peuvent s'installer. Parmi les multiples facteurs qui peuvent affecter l'équilibre électrophysiologique cardiaque, il faut noter une maladie métabolique dont la prévalence ne cesse d'augmenter dans la population mondiale : le diabète de type 2. En effet, cette maladie augmente les risques de souffrir d'arythmie. Nous avons d'abord développé un modèle de cobaye diabétique de type 2 par une alimentation avec une diète spéciale sur une période de 200 jours. Ces animaux nous ont permis d'obtenir nos résultats dans des conditions ex- et in-vivo. Par la suite, nous avons évalué une hypothèse selon laquelle, en présence de diabète, l'ajout d'un bloquant d'IcaL évite la prolongation excessive du QT et la pro-arythmie, lorsque d'autres médicaments prolongeant le QT sont utilisés de manière concomitante. Nous avons quantifié l'effet de l'amlodipine (Norvasc®), un médicament bloquant d'IcaL et du dofétilide (Tikosyn®), un médicament bloquant d'iKr- Les résultats obtenus ont montré que l'amlodipine renverse partiellement l'effet pro-arythmique du dofétilide et protège contre la prolongation excessive de l'intervalle QT et la pro-arythmie médicamenteuse, particulièrement en présence de diabète de type 2. En parallèle, nous avons qualifié et quantifié l'effet pro-arythmique du bupropion (Wellbutrin®, Zyban®), un antidépresseur et adjuvant à la cessation tabagique. Des élargissements du QRS avaient été rapportés lors de surdosages de bupropion. Nous avons voulu vérifier l'hypothèse selon laquelle le bupropion affecte la conduction cardiaque par un bloc des jonctions gap. À l'aide des résultats obtenus, nous avons pu dire que, contrairement aux anti-arythmiques de classe I, le bupropion n'élargit pas le QRS en bloquant IN3, mais plutôt en inhibant les jonctions gap. C'est une propriété pharmacologique exceptionnelle observée chez aucun autre médicament actuellement disponible sur le marché. L'élargissement du QRS et les troubles de conduction cardiaques s'observent à des concentrations de bupropion facilement atteignables en clinique.

O objetivo deste trabalho foi estudar o efeito da radioterapia na profilaxia da ossificação heterotópica (OH) em pacientes com lesão medular traumática. Foram estudados 19 pacientes (15 homens e quatro mulheres), média de idade de 30,4 ± 10,8 anos (19 a 58 anos), com lesão medular traumática. A causa mais freqüente da lesão medular foi acidente de trânsito (42,1%), seguida por queda (26,3%), ferimento por projétil de arma de fogo (21%), mergulho (5,3%) e queda de objeto sobre as costas (5,3%). Dez pacientes eram tetraplégicos (52,6%) e nove (47,4%) eram paraplégicos. Apresentavam lesão medular completa (Frankel A) 14 pacientes (73,7%) e cinco pacientes (25,3%) tinham lesão incompleta (Frankel B). Todos os pacientes incluídos no estudo realizaram cintilografia óssea inicial até um mês após o traumatismo raquimedular e apresentaram diagnóstico negativo para OH. Os pacientes foram divididos em dois grupos: nove pacientes receberam radioterapia em dose única de 8 Gy nos quadris (Grupo Estudo) e 10 pacientes compuseram o Grupo Controle. Após seis meses de seguimento clínico e radiológico, um paciente do Grupo Estudo (11%) e cinco pacientes do Grupo Controle (50%) apresentaram OH. A distribuição da freqüência do desenvolvimento da OH nos dois grupos não mostrou diferença estatística significante, apesar da menor incidência de OH no grupo submetido à radioterapia (Grupo Estudo). Concluiu-se que, com o número de pacientes estudados, não foi possível comprovar a eficácia da radioterapia na prevenção da ossificação heterotópica, ainda que haja uma forte tendência para a correlação estatística / The goal of this study was to evaluate the effect of radiotherapy on the prophylaxis of heterotopic ossification (HO) after spinal cord injury (SCI). Nineteen SCI patients were studied (15 men and four women). The mean age was 30.4 ± 10.8 years (range 19 to 58 years). The most frequent causes of lesion were traffic accident (42.1%), fall (26.3%), shot gun (21%), diving (5.3%) and objects falling on the vertebral column (5.3%). Ten patients were tetraplegics (52.6%) and nine were paraplegics. Fourteen patients (73.7%) had complete lesion (Frankel A) and five had incomplete lesion (Frankel B). All patients realized initial scintigraphy until one month after SCI and showed negative results for HO. The patients were randomized in two groups: nine patients received single dose irradiation with 8 Gy on the hips (Study Group) and 10 patients were the Control Group. After six months of clinical and radiological follow up, one patient of the Study Group (11%) and five patients of Control Group (50%) showed HO. The frequency distribution of the development of HO in both groups showed no significant statistical difference, although there was lower incidence of HO in the radiotherapy group. We concluded that, with the number of patients studied, it was no possible to prove the efficacy of radiotherapy to prevent HO, although had a strong tendency for the statistical correlation