Ethical decisions about medical care of infants is based on the by proxy evaluation of the infants' best interests. Since parents and physicians may have different points of reference, conflicts may arise during the decision-making process. The decision about the infant's well being becomes even more complex when high risk treatment with an uncertain long-term outcome is considered. Surgical palliation of hypoplastic left heart syndrome (HLHS) is an example of such a treatment. I use this example in my discussion on the relevant ethical issues and possible roots of conflicts between the decision-makers. / I argue that as long as long-term survival rates are variable, and the survivors' quality of life remains uncertain, palliative surgery for HLHS should not be obligatory. Rather, the parents should be informed not only about the existing treatments but also about the non-treatment option, and what each option may imply for the infant, parents and the family.

The aim of this study was to: (a) identify risk factors for the development of venothromboembolism in a trauma population, (b) evaluate whether risk factors vary with increasing Injury Severity Score (ISS), and (c) assess the predictive ability of the Risk Assessment Profile for Thromboembolism (RAPT) in this trauma population. There were 7532 admissions for trauma between 1993 and 1998 to the Montreal General Hospital trauma center. A nested case-control design was used. Cases were defined as all patients with radiological evidence of either a deep venous thrombosis or pulmonary embolus during their admission. Controls were patients satisfying the same inclusion criteria who did not suffer a symptomatic deep venous thrombosis or pulmonary embolism while in hospital, did not have evidence of deep venous thrombosis prior to the traumatic event, and found to be free of any symptomatic thromboembolic events on consequent follow up. Patients were divided into three categories, ISS 1--24 (mild-moderate injuries), ISS 25--59 (moderate-severe injuries), and ISS 60--75 (severe-fatal injuries). (Abstract shortened by UMI.)

Objective. To compare the prognostic ability of first available measurements of CD4 cell count and viral load with that of the most recent measurements and to assess the additional prognostic ability of the values of past measurements of these markers. / Methods. Demographic and clinical information on 965 HIV-1 infected adults followed at a university-based HIV clinic in Montreal, Quebec were extracted from a clinical database. The prognostic ability of initial and most recent CD4 cell count and viral load measurements were assessed in a series of Cox models. The added prognostic ability of past values of measurements of these markers was explored by calculating; (i) the unweighted mean values of all previous measurements and (ii) a time-weighted mean. The differences between these mean levels and the most recent values were included as time-dependent covariates in Cox models adjusted for the value of the most recent measurements. / Conclusion. The most recent measurements of CD4 cell count and viral load are more powerful predictors of clinical disease progression than initial measurements. (Abstract shortened by UMI.)

Distraction osteogenesis (DO) is a surgical technique used to treat limb length discrepancies, limb deformities, long bone non-unions and bone loss due to trauma, infection or malignancies. In this surgical method a transverse osteotomy is performed and the fractured bone is stabilized using the Ilizarov fixation system. After a short latency period, the two ends of the fractured bone are slowly pulled apart, stimulating new bone formation within the distracted gap. After the distraction is completed, the newly formed bone is allowed to fully consolidate. One of the main limitations of DO is the long consolidation period required for the bone to heal. Different methods have been researched to accelerate the consolidation phase of DO, including the exogenous application of bone morphogenetic proteins (BMPs). BMPs are growth factors that are required in the bone developmental pathway. Although numerous studies have tested pharmacological doses of BMP2 and BMP7 using different animal models of DO, the physiological role of BMPs during DO still remains poorly understood. Hence, in this study we investigated the physiological role of BMP2 in a heterozygous conditional BMP2 knockout model of distraction osteogenesis. Distraction osteogenesis was performed on the right tibia of forty wild-type BMP2 fl/+ mice and heterozygous BMP2 fl/+ cre mice using a miniature version of the Ilizarov fixator. Mice underwent a latency period of 5 days, a distraction period of 12 days (distraction rate of 0.2 mm every 12 hours) and a consolidation period of 34 days. Distracted samples were collected from four time points: 11 days (mid-distraction phase), 17 days (end of distraction phase), 34 days (mid-consolidation phase) and 51 days (end of consolidation phase). Samples were studied using µCT, Faxitron x-ray, immunohistochemistry, histology, Real Time-quantitative PCR and biomechanical testing. Results from this study showed that reducing BMP2 expression through gene d / L’ostéogenèse par distraction (OD) est une technique chirurgicale utilisée pour traiter des dissymétries des membres et des défauts osseux suite à un traumatisme, une infection ou une maladie. Dans cette méthode, une ostéotomie est faite et l'os fracturé est stabilisé par un fixateur externe de type Ilizarov. Durant la période de distraction, les extrémités de l'os sont tirées lentement l'une de l'autre, ce qui stimule la nouvelle formation d'os dans la zone de distraction. Ensuite, la phase de consolidation permet l’ossification de tissu nouvellement formé.Le problème principal de l’OD est que la période de consolidation est très longue. De recherches ont été faites afin d’accélérer la phase de consolidation de l’OD tel que l'application des protéines de la morphogenèse osseuse (BMP). Les BMP sont nécessaires pour le développement osseux. Bien que beaucoup d’études ont analysé les effets de doses pharmacologiques de BMP2 et BMP7 en utilisant des modèles animaux de l’OD, le rôle physiologique des BMP est encore inconnu. Donc, pour cette étude nous avons analysé le rôle physiologique de BMP2 durant l’OD chez des souris ayant une déficience en BMP2 localisée dans les membres. Nous avons soumis le tibia droit de souris contrôle-BMP2 fl/+ et de souris hétérozygotes-BMP2 fl/+ cre à l’ostéogenèse par distraction en utilisant un fixateur Ilizarov miniaturisé. Les souris ont subi une période de latence de 5 jours, une période de distraction de 12 jours (avec un taux de distraction de 0.2 mm chaque 12 heures), et une période de consolidation de 34 jours. Les échantillons ont été recueillis à 11, 17, 34 et 51 jours, et analysés par µCT, rayons X, immunohistochimie, histologie, par PCR en temps réel, et par un examen biomécanique.Les résultats de cette étude ont montré que la diminution de l’expression de BMP2 dans les membres hétérozygotes avait pour effet de ralentir le processus de con

The accumulation of fat in the marrow cavity is a consequence of the predominant mesenchymal stem cell differentiation into the adipocyte fate at the expense of the osteoblasts. Considering that these changes in stromal differentiation have an effect on bone health, we attempted to study bone marrow fat depots from a metabolic, lipotoxic and regulatory approach. In a fist attempt to study the potential metabolic role of bone marrow fat we observed the effect of calorie restriction (CR) on bone quality and marrow fat of aging rats subjected to a casein and soy protein diet. Bone quality and adipocyte quantification was obtained from rat tibia. Bone as well as adipogenic markers were quantified. CR was found to induce a significant decrease in bone quality. In contrast to CR rats, the ad libitum soy fed rats showed an overall better bone quality. Moreover, the results obtained showed that adipocytes were not mobilized during CR as no changes in leptin levels or adipocyte number were found. Finally we noticed that soy protein and not CR inhibited PPARgamma expression, a transcription factor required for adipogenesis. In summary, results from this first approach showed that bone marrow fat does not participate in lipid metabolism during moderate stages of starvation and that the detrimental effect of CR on bone mass could be prevented using a soy protein regime. A second approach to this subject involved looking at the mechanism through bone and fat interact within the bone marrow. We hypothesized that bone marrow adipocytes’ secretion of fatty acids (FA) induces changes in osteoblast differentiation, function and survival compatible with lipotoxicity. Using a co culture system of human pre-adipocytes and osteoblasts we showed that FAs negatively affect osteoblast differentiation and mineralization. Furthermore the effect could be prevented through the use of a FA syntase inhibitor, cerulenin. Gas chromatography/ mass spectrometry (GC\MS) analysis of co-culture su / L’ostéoporose sénile est souvent associée à une augmentation de gras dans la moelle osseuse. Cette accumulation de gras est une conséquence d’une différentiation prédominante de cellules souches en adipocytes en lieu d’ostéoblastes. Prenant en considération ce changement de différentiation, nous avons décidé d’étudier le gras de la moelle osseuse de trois différentes approches : métabolique, lipo-toxique et régulatrice. Nous avons premièrement observé les effets d’une restriction calorique (RC) sur la qualité osseuse ainsi que sur le gras de la moelle osseuse de rats nourris de caséine ou de soja. Les marqueurs osseux et adipogéniques ont aussi été quantifiés. La RC fut identifiée comme une cause de réduction de qualité osseuse. Contrairement aux rats subjugués à une RC, les rats qui furent subjugués à une diète « ad libitum » de soja ont démontré une qualité osseuse supérieure. Aucuns changements n’ont été identifiés quant aux niveaux d’expression de leptin ou de cellules grasses. Ces derniers résultats indiquent que les cellules grasses de la moelle osseuse ne sont pas mobilisées pendant les périodes de RC. La diète de soja est responsable pour l’attenuation de l’expression de PPARgamma .Les résultats de l’étude ont démontré en premier lieu que le gras de la moelle osseuse ne participe pas au métabolisme de lipides pendant les périodes de famines modérées ; puis en deuxième lieu que les effets de la RC sur les os peuvent être diminués par une diète de soja. En deuxième lieu, nous avons observé le mécanisme par lequel le gras de la moelle participe à la perte osseuse associé au vieillissement. Un modèle de co-cultures cellulaires de pré-adipocytes humains ainsi que d’ostéoblastes nous a permis de démontrer que les acides gras (AG) sécrétés par les adipocytes ont un effet inhibant sur la différentiation ainsi que sur la minéralisation des ostéoblastes. Aussi, nous av

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No description available.

Ventilation is frequently used in the treatment of cardiogenic and increased permeability pulmonary edema. The effects of ventilation on the computed tomography (CT) density distribution of pulmonary edema are unclear. We hypothesized that ventilation might open up previously collapsed alveoli with consequent reduced lung density, and that some movement of the alveolar edema fluid might also occur from the alveoli to the interstitium. To address this problem, pulmonary edema was induced in 16 supine dogs by airways instillation of a protein solution similar to serum in each lower lung lobe through a double lumen tracheal tube. The dogs were ventilated only on the left side for 1 min (n = 4), 30 min (n = 6) or 60 min (n = 6). The lower lobes were excised, frozen in liquid nitrogen, and imaged in a CT scanner. Representative regions of interest (ROI) were chosen and tissue sections from corresponding regions were taken for extravascular lung water (Qwl/dQl) and regional blood measurements, and for histology to grade interstitial and alveolar edema. There was a significant (P $<$ 0.05) fall in the CT density of the left lower lobes compared with the right lower lobes in the groups ventilated 30 and 60 min, but no differences in Qwl/dQl or blood content. The histological grading showed a trend (P = 0.054) for more interstitial edema in the left lower lobes in the 60 min ventilation group compared with left lower lobes in the 1 min ventilation group. These data show that in our model of instilled alveolar edema, ventilation acts primarily by increasing aeration by 30 min and that it has a minor role in moving fluid to the interstitium.

No description available.

This thesis reviewed current theories of the post-ischemic injury. Special emphasis was placed on the concept of reperfusion injury. / In a series of four experiments, this thesis evaluated neutrophil function, localization, depletion, and inhibition in ischemic cutaneous and myocutaneous flaps. Neutrophil function as measured by phorbol myristate acetate stimulated superoxide production was found to be enhanced on reperfusion of ischemic myocutaneous flaps. $ sp{111}$Indium labelled neutrophils were found to localize in post-ischemic cutaneous and myocutaneous flaps. Post-ischemic cutaneous flap survival was not improved by either cyclophosphamide induced neutrophil depletion or ibuprofen neutrophil inhibition. Post-ischemic myocutaneous flap survival was significantly improved by both cyclophosphamide induced neutrophil depletion and ibuprofen neutrophil inhibition. Thus, the cumulative evidence from these experiments yielded surprisingly different conclusions for cutaneous and myocutaneous flaps. The post-ischemic injury in cutaneous flaps was not mediated by the neutrophil. In contrast, the neutrophil did partially mediate the complex post-ischemic injury of myocutaneous flaps.