A major obstacle to islet transplantation is β-cell death following isolation. Isolation exposes islets to various stresses including endoplasmic reticulum (ER) stress inducers; therefore, the role of ER stress signaling in isolated islet apoptosis was investigated. Activation of eIF2α and JNK1 and XBP1 splicing followed by an increase in caspase-3 activity were observed in isolated human islets. Since the absence of protein-tyrosine phosphatase 1B (PTP1B) was previously shown to reduce ER stress-induced signaling and apoptosis in fibroblasts, the role of PTP1B in ER stress signaling was investigated in β-cells. While encouraging data emerged, using an inhibitor and miRNA targeting PTP1B, a conclusive link between PTP1B inhibition and improved β-cell survival has not yet been seen. This study provides the first evidence that ER stress signaling may influence isolated islet apoptosis and could point to novel therapeutic approaches in islet transplantation. / Un obstacle majeur lors de la transplantation des îlots pancréatiques est la perte des cellules β lors de la procédure d'isolation. En effet, lors de ce processus, les îlots sont exposés à divers stress cellulaires incluant ceux qui induisent un stress au niveau du réticulum endoplasmique (RE). Cette étude porte donc sur la signalisation menant à l'apoptose en réponse au stress du RE sur les îlots isolés. L'activation d'eIF2α, de JNK1 et de l'épissage de XBP1 qui est suivi par une augmentation de l'activité de la caspase-3 fut observées sur des îlots isolés chez l'humain. L'absence de la protéine tyrosine phosphatase 1B (PTP1B) avait précédemment été démontrée comme pouvant contribuer à la diminution de la signalisation déclenchée par le stress du RE et l'apoptose chez les fibroblastes. Malgré des résultats encourageants concernant l'utilisation d'un inhibiteur et d'un miRNA qui ciblent PTP1B, un lien concluant entre l'inhibition de cette enzyme et l'amélioration de la survie des cellules β n'a pas été observé Cette étude fournit la première évidence qui clarifie le rôle de la signalisation induite par le stress du RE lors de l'apoptose des îlots pancréatiques. De plus, elle pourrait résulter en une nouvelle approche thérapeutique pour augmenter la survie des cellules β lors de la transplantation d'îlots.

The effects of reversible fetal tracheal occlusion (TO), and antenatal glucocorticoids on lung growth, structure, surfactant levels, and function were assessed in a lamb hypoplastic lung model of congenital diaphragmatic hernia (CDH). CDH, CDH+TO, CDH+TO+release of the tracheal occlusion one week before delivery (TR), and unoperated twin controls were compared. TO+/-TR partially normalized the hypoplastic lungs of CDH: they accelerated growth of both lungs and led to structural maturity. Only TO thinned the medial area of small pulmonary arteries closer to control values. Despite TO, TR, and glucocorticoids, lungs from lambs with CDH have dysfunctional type II cells with decreased surfactant levels. Nonetheless, CDH+TO lambs showed normal oxygenation, ventilation, and compliance over untreated CDH, with a clear survival advantage over an eight hour resuscitation. TR one week before delivery had no added benefit in terms of lung function. It appears that surfactant independent mechanisms such as pulmonary growth and structural changes are of foremost importance in relating to improved compliance, oxygenation, and ventilation of CDH+TO animals.

Context. Exacerbations of chronic obstructive lung disease (COPD) that result in acute respiratory failure are a significant health care problem with high morbidity and mortality. Recent reports have shown that preventing intubation with the use of non-invasive positive pressure ventilation significantly decreases the morbidity and mortality associated with respiratory failure in this population. / Objective. To evaluate whether patients with COPD and acute respiratory failure treated with non-invasive continuous positive airway pressure (CPAP) have improved clinical outcomes after adjusting for potentially confounding covariates when compared to similar patients who were intubated or treated with medical therapy. / Design and setting. Comparison of three retrospective cohorts, one in which CPAP was routinely available and two in which CPAP were not available for the management of this type of patient. Data were collected on all patients admitted to two ICU's in tertiary care teaching hospitals during the time periods defined by the cohorts. / Population. Two hundred and thirty-eight patients with chronic obstructive lung disease and acute respiratory failure admitted to two intensive care units between January 15th 1985 to December 31st 1995. (Abstract shortened by UMI.)

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Standard therapy for abdominal aortic graft infection involving resection of the graft and extranatomic bypass, carries significant morbidity and mortality due to aortic stump rupture and limb loss. This thesis evaluates the feasibility of combining in situ graft replacement with a highly vascular tissue flap as an alternative approach to this problem. / In sixty-nine pigs, a segment of a polytetrafluoroethylene (PTFE) graft was interposed in the infrarenal abdominal aorta. Staphylococcus aureus was then used to infect the graft. One week later the animals were divided into six treatment groups where two different types of pedicled muscle flaps were used to treat the infection. The flaps were designed from the rectus abdominis and the seromuscularis of the jejunum. / The results showed that graft infection could be controlled if either of the muscle flaps were used. Graft thrombosis did not occur if the infected graft was changed with a new PTFE graft. / Vascularized tissue flaps avoid thus potentially fatal aortic stump rupture and may improve limb salvage in this difficult clinical problem.

Early hypertrophy has justified the clinical use of vascularized bone grafts. This hypertrophy has not been established in experimental models, possibly because stress-shielded grafts were used. Our model allowed the grafts to bear weight. In 14 dogs we replaced the diaphysis of the radius with a vascularized fibula, and the diaphysis of the ulna with a conventional fibula (Group I). In 10 dogs we reversed the positions of the grafts (Group II). External fixation was used. The grafts were evaluated radiographically, mechanically and histologically. The vascularized grafts hypertrophied early, and were stronger than conventional grafts, particularly in Group I, where the former were stressed more. A previously unreported repair pattern was observed: vascularized grafts increased in size by peripheral apposition of new bone, there was no creeping substitution or weakening resorption. Conventional grafts remodeled by creeping repair, and hypertrophied slower, never reaching the size or the strength of the vascularized grafts.

The meniscus is essential for normal knee function. Previously considered unimportant, removal was performed when injured. This frequently led to degenerative arthritic changes. Today surgeons attempt to repair or minimally resect torn menisci, however many patients are encountered with irreparable tears or previously removed menisci. In these patients meniscale transplantation may prevent degenerative arthritis from developing. / Problems facing transplantation are ability to store tissues and prevent disease transmission. To overcome this, freezing and irradiation effects were examined on 60 rabbits undergoing medial meniscal transplantation. Fresh, frozen, and frozen-irradiated allografts were followed up to 17 months, 10 other rabbits underwent meniscectomy alone. / Zero-time studies revealed that freezing with or without irradiation rendered cells non-viable with no changes in mechanical properties. At long term follow-up, all grafts healed, and showed repopulation with metabolically active cells determined radioautographically. Mechanical properties were unchanged, except for a decreased time constant in the frozen group. Degenerative changes were not significantly different among groups.

Background: High frequency oscillations (HFOs) are transient electroencephalographic events that may play a role in epileptogenesis. Initially detected using microcontacts (10-3 mm2), they can be recorded using macrocontacts (1 to 20 mm2). It has been demonstrated that microcontacts detect HFOs better than macrocontacts. Given the wide range of clinical contact sizes, it was hypothesized that smaller macrocontacts detect HFOs better than larger macrocontacts. / Methods: Rates, characteristics and cross correlation of HFOs, coherence and amount of artefact were compared between the recordings from adjacent contacts of electrodes containing contiguous macrocontacts of different sizes, in 10 patients and 8 experimental animals. / Results: Rates and characteristics were not significantly different between the different contact sizes. Differences in coherence and artefact were not significant. Conclusion: In the range tested, contact size did not affect HFO detection rate. Further study remains to be done to determine if larger contact sizes than those evaluated here are also equivalent. / Introduction : Les oscillations de haute fréquence (high frequency oscillations, HFOs) sont de brefs phénomènes électroencéphalographiques qui pourraient jouer un rôle dans l'épileptogénèse. Initialement décrites à partir d'enregistrements à l'aide de microcontacts (10-3 mm2), les HFOs peuvent aussi être enregistrées par des macrocontacts (1 à 20 mm2), mais ces derniers paraissent moins efficaces à les détecter. Vu le spectre de tailles des macrocontacts, nous avons supposé que de plus petits macrocontacts détectent mieux les HFOs que de plus grands / Méthodes : Les taux de détection, caractéristiques et corrélation croisée des HFOs, ainsi que la cohérence et les artéfacts de l'EEG, ont été comparés entre des enregistrements intracrâniens provenant de contacts contigus mais de taille différente chez 8 rats expérimentaux et 10 patients. / Résultats : Aucune différence significative de taux, caractéristiques, cohérence ni artéfact n'a été décelée. Conclusion : A l'intérieur du spectre de tailles étudiées, la taille du contact n'influence pas la détection des HFOs. Il reste à déterminer si des macrocontacts plus grands demeurent aussi efficaces.