No description available.

The catheterised urinary tract constitutes an ideal niche for bacterial colonisation, with an estimated 80% of all nosocomial urinary infections attributed to the presence of an indwelling catheter. The present thesis describes the rational design and development of three novel drug delivery systems for application as infection-resistant catheter coatings, which respond to the alkaline conditions generated at the onset of urinary catheter infections by urease-producing pathogens, particularly Proteus mirabilis, via the release of drugs. Upon probing P. mirabilis biofilms with a pH microelectrode, values up to pH 10.12 were recorded directly within the biofilm micro environment. In addition to exploiting this pH elevation to act as a trigger for drug release, the effect of pH on quinolone antibacterial activity is reported herein. Specifically, bactericidal potency of the fluoroquinolone agents: norfloxacin and ciprofloxacin, against P. mirabilis was observed to increase with elevated pH, whereas high concentrations of nalidixic acid demonstrated bactericidal activity selectively in alkaline environments, in contrast to the characteristic 'paradoxical' survival of bacteria observed with high concentrations of this agent in acidic and neutral media. In the first drug delivery system developed herein, the inherent pH -dependent physicochemical properties of nalidixic acid were exploited by a novel, surface particulate localisation method to achieve up to 50-fold faster drug release at pH 9 , than at normal physiological urine pH values ranging from pH 5 to pH 7. In contrast to physical drug loading, the final two systems focused on chemical conjugation of nalidixic acid and surfactant moieties via labile ester bonds to hydrogel backbones. Release of the covalently attached agents was successfully delayed at pH 7 compared to the significantly faster rates of ester hydrolysis and subsequent release at pH 10. Comparative differences in the resistances to bacterial adherence relative to the control hydrogel were demonstrated depending on the specific conjugated agent.

No description available.

Indwelling urethral catheters are the most commonly used medical devices and catheter associated urinary tract infections (CAUTIs) are one of the most common hospital acquired infections. Over 40% of CAUTIs in long-term catheterised patients may be caused by the bacterium Proteus mirabilis. Urease produced by this bacterium generates alkaline conditions by breaking down urea, leading to the formation of dense crystalline biofilm structures on catheter surfaces. This crystalline biofilm makes infections hard to treat and causes the blockage of the catheter lumen, resulting in the retention of infected urine leading to episodes of ascending urinary tract infections. The aim of this study was to identify genes and pathways involved in crystalline biofilm formation by P. mirabilis, in order to inform the development of novel strategies for prevention of catheter blockage. To accomplish this, a bank of random mini-Tn5 transposon mutants was constructed in the clinical isolate P. mirabilis B4. A total of 3840 transposon mutants were screened for phenotypic alterations in biofilm formation. A total of 575 mutants isolated exhibited altered biofilm formation, but comparable rates of growth to P. mirabilis B4 under assay conditions (310 biofilm enhanced; 265 biofilm deficient). The disrupted genes of a subset of 35 transposon mutants were successfully identified. After further phenotypic characterisation 12 transposon mutants were selected and their ability to encrust and block urethral catheters analysed using an in vitro model of the catheterised urinary tract (the bladder model). The bladder models yielded 4 transposon mutants with significant differences in the time taken to block catheters when compared to P. mirabilis B4. Two blocking deficient mutants were further analysed because these types of mutations are most likely to give insights relevant to the prevention of crystalline biofilm formation. Mutants STS8.1D7 and NHBFF9 were disrupted in aspects of the nitrogen metabolism and MFS family transport systems respectively. Timed bladder model experiments and chemical analysis of catheters of these mutants and the wild type B4 were then carried out to further evaluate the differences in crystalline biofilm formation. Overall, transposon mutants that took longer to block catheters displayed a lower level of encrustation after 10 h bladder model experiments. This was confirmed quantitatively by a significant reduction in calcium and biomass deposited onto catheters. Scanning electron microscopy (SEM) and environmental SEM (ESEM) further substantiated the quantitative methods illustrating clear differences in crystalline biofilm distribution for mutants that took longer to block catheters when compared to P. mirabilis B4. ESEM analysis optimized for this purpose allowed the examination of the crystalline biofilm ultrastructure in fine detail in its native, hydrated state and identified delicate calcium based crystal sheets which had not been visualised before. Additional flow chamber experiments confirmed that the ability of the two mutants to adhere to catheter biomaterials was not impaired, highlighting that the initial stages of biofilm formation were not associated with the genes disrupted for these mutants. Overall, the research conducted during this study identified 4 mutants differing in the time taken to block catheters, elucidating 4 genes that are involved in this complex phenotypic trait. Mutants with significant reductions in the ability to block urinary catheters displayed disruptions of the nitrogen metabolism and efflux systems which are believed to be involved in waste management in this bacterium. The inhibition of efflux systems in particular could be of potential value in the treatment or prevention of P. mirabilis crystalline biofilm formation by increasing its susceptibility to antimicrobials, and further investigation of these genes in the future could lead to the development of novel treatments for P. mirabilis CAUTIs.

This thesis describes the work carried out on the development of a novel digit actuator system with tactile perception feedback to a user and demonstrated as a master-slave system. For the tactile surface of the digit, contrasting sensor elements of resistive strain gauges and optical fibre Bragg grating sensors were evaluated. A distributive tactile sensing system consisting of optimised neural networking schemes was developed, resulting in taxonomy of artificial touch. The device is suitable for use in minimal invasive surgical (MIS) procedures as a steerable tip and a digit constructed wholly from polymers makes it suitable for use in Magnetic Resonance Imaging (MRI) environments enabling active monitoring of the patient during a procedure. To provide a realistic template of the work the research responded to the needs of two contrasting procedures: palpation of the prostate and endotracheal intubation in anaesthesia where the application of touch sense can significantly assist navigation. The performance of the approach was demonstrated with an experimental digit constructed for use in the laboratory in phantom trials. The phantom unit was developed to resemble facets of the clinical applications and digit system is able to evaluate reactive force distributions acting over the surface of the digit as well as different descriptions of contact and motion relative to the surface of the lumen. Completing control of the digit is via an instrumented glove, such that the digit actuates in sympathy with finger gesture and tactile information feedback is achieved by a combination of the tactile and visual means.

Accompanying CD-ROM contains image files and software. / Bibliography: leaves 259-286. / xvi, 286 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Explores the factors affecting the movement of tumour cells from a primary malignancy across the peritoneal cavity to the port-site following laparoscopic intervention. Filter methods and radio-labelled tumour cells provided the most useful way of following cell movement. Concludes spread of tumour cells to the port-site is more likely in the presence of disseminated disease, as well as with inappropriate surgical technique. Metastasis may be reduced by the use of intraperitoneal lavage and appropriate surgical technique. / Thesis (M.D)--University of Adelaide, Dept. of Surgery, 1999

L’objectif de notre travail était, d’une part, de déterminer l’impact du délai de transmission des informations en téléchirurgie robotique, et d’autre part, de valider le rôle du simulateur robotique dans la formation en chirurgie robotique. Deux études ont été réalisées pour la partie concernant le délai. Il a été prouvé que la performance chirurgicale se détériore exponentiellement lorsque le délai augmente. Il est préférable d’envisager un geste de téléchirurgie associé à un délai inférieur à 200 ms, et des délais plus de 800 ms ne sont pas adaptés à la téléchirurgie. D’autre part, les chirurgiens ont démontré la capacité de s’adapter au délai par l’entraînement. Dans la deuxième partie, nous avons développé un curriculum sur un simulateur robotique pour une procédure chirurgicale robotique d’urologie. Une autre étude a été réalisée pour déterminer la validité d’un nouveau simulateur robotique (le XTT) comme un outil d’évaluation des techniques d’assistance en chirurgie robotique. / The objectives of our work were, on the one hand, to determine the impact of data-transmission latency in robotic telesurgey, and on the other hand, to validate the role of robotic simulator in robotic surgery training. Two studies were realized in the part concerning latency. It was proved that surgical performance deteriorates exponentially as latency increases. It is preferable to perform telesurgey with a delay less than 200 ms. The delay higher than 800 ms is not suitable for telesurgery. On the other hand, surgeons had demonstrated the capacity to adapt to delay through training. In the second part, we developed a curriculum on a robotic simulator for a urologic surgical procedure. Another study was realized to determine the validity of a new robotic simulator (the XTT) as an evaluation tool of robotic surgical assistance skills.

L'évolution des techniques chirurgicales, par l'utilisation de robots, permet des interventions mini-invasives avec une très grande précision et ouvre des perspectives d'interventions chirurgicales à distance, comme l'a démontré la célèbre expérimentation « Opération Lindbergh » en 2001. La contrepartie de cette évolution réside dans des volumes de données considérables qui nécessitent des ressources importantes pour leur transmission. La compression avec pertes de ces données devient donc inévitable. Celle-ci constitue un défi majeur dans le contexte médical, celui de l'impact des pertes sur la qualité des données et leur exploitation. Mes travaux de thèse concernent l'étude de techniques permettant l'évaluation de la qualité des vidéos dans un contexte de robotique chirurgicale. Deux approches méthodologiques sont possibles : l'une à caractère subjectif et l'autre à caractère objectif. Nous montrons qu'il existe un seuil de tolérance à la compression avec pertes de type MPEG2 et H.264 pour les vidéos chirurgicales. Les résultats obtenus suite aux essais subjectifs de la qualité ont permis également de mettre en exergue une corrélation entre les mesures subjectives effectuées et une mesure objective utilisant l'information structurelle de l'image. Ceci permet de prédire la qualité telle qu'elle est perçue par les observateurs humains. Enfin, la détermination d'un seuil de tolérance à la compression avec pertes a permis la mise en place d'une plateforme de transmission en temps réel sur un réseau IP de vidéos chirurgicales compressées avec le standard H.264 entre le CHU de Nancy et l'école de chirurgie / The digital revolution in medical environment speeds up development of remote Robotic-Assisted Surgery and consequently the transmission of medical numerical data such as pictures or videos becomes possible. However, medical video transmission requires significant bandwidth and high compression ratios, only accessible with lossy compression. Therefore research effort has been focussed on video compression algorithms such as MPEG2 and H.264. In this work, we are interested in the question of compression thresholds and associated bitrates are coherent with the acceptance level of the quality in the field of medical video. To evaluate compressed medical video quality, we performed a subjective assessment test with a panel of human observers using a DSCQS (Double-Stimuli Continuous Quality Scale) protocol derived from the ITU-R BT-500-11 recommendations. Promising results estimate that 3 Mbits/s could be sufficient (compression ratio aroundthreshold compression level around 90:1 compared to the original 270 Mbits/s) as far as perceived quality is concerned. Otherwise, determining a tolerance to lossy compression has allowed implementation of a platform for real-time transmission over an IP network for surgical videos compressed with the H.264 standard from the University Hospital of Nancy and the school of surgery

Le développement croissant de la chirurgie robotique pose le problème de la formation. Cette nouvelle technologie tend à suppléer dans les procédures complexes la coelioscopie. Elle nécessite une adaptation du chirurgien. Il est, en effet, nécessaire de maîtriser à la fois le télémanipulateur et les procédures chirurgicales, qui ne sont pas de simples transpositions des gestes coelioscopiques. Initialement, nous avons réalisé un historique du développement de la chirurgie mini-invasive coelioscopique et robotique, ainsi qu'un historique de l'apprentissage de la chirurgie. Puis, nous nous sommes intéressés à l'apprentissage de la robotique. Les simulateurs de chirurgie coelioscopique sont très couramment employés dans l'apprentissage. En robotiques, ils ont fait récemment leur apparition sur le marché. Nous avons étudié la validité du simulateur dV-Trainer dans l'apprentissage de la chirurgie robotique. Nous avons démontré l'intérêt de cet outil dans l'acquisition de la gestuelle et des automatismes propres au robot. Nous avons par ailleurs étudié l'impact d'une formation en micro-chirurgie sur les performances développées en chirurgie robotique car, au cours d'une étude préliminaire nous avions constaté que les micro-chirurgiens présentaient de meilleures aptitudes sur le simulateur de chirurgie robotique que ceux sans expérience en micro-chirurgie. Dans un troisième temps, nous nous sommes intéressés à la téléchirurgie à longue distance qui est impactée par deux contraintes que sont la latence de transmission et le volume des informations à transmettre. Une première étude a étudié l'impact du délai de transmission sur les performances des chirurgiens. Une deuxième étude a consisté à réaliser une évaluation subjective par des chirurgiens de la qualité de vidéos de chirurgie robotique compressées afin de déterminer un seuil de compression maximal acceptable / The huge expansion of minimally invasive robotic devices for surgery ask the question of the training of this new technology. Progress of robotic-assisted surgical techniques allows today mini- invasive surgery to be more accurate, providing benefits to surgeons and patients for complex surgical procedures. But, it resulted from an increasing need for training and development of new pedagogical strategies. Indeed, the surgeon has to master the telemanipulator and the procedure, which is different from a simple transposition of a laparoscopic skill. The first part of this work treats about historical development of minimal invasive surgery from laparoscopy to robotic surgery. We also develop the evolution of training program in surgery. Virtual simulators provide efficient tools for laparoscopy training. The second part of this work, study some possible solutions for robotic training. We assess the validity of a new robotic virtual simulator (dV-Trainer). We demonstrate the usefulness of this tool for the acquisition of the basic gesture for robotic surgery. Then, we evaluate the impact of a previous experience in micro-surgery on robotic training. We propose a prospective study comparing the surgical performance of micro-surgeons to that of general surgeons on a robotic simulator. We want to determine if this experience in micro-surgery could significantly improve the abilities and surgeons performance in the field of basic gesture in robotic surgery. The last part of the study also looks to the future. Currently, telesurgery need sophisticated dedicated technical resources. We want to develop procedures for clinical routine used. Therefore, we evaluate the impact of the delay on the surgical procedure. Also, reducing data volume allow decreasing latency. An appropriate solution to reduce the amount of data could be found by introducing lossy compression for the transmission using the well-known MPEG-2 and H-264 standards

Le facteur pronostic majeur des cancers du col localement avancés (LACC) est le statut ganglionnaire lombo-aortique. Notre travail de thèse a été d'évaluer la lymphadénectomie lombo-aortique (qui représente la technique de référence pour obtenir cette information) à l'ère de la tomographie par émission de positron (TEP) et de la chirurgie par une seule incision (LESS). Les résultats publiés de cette thèse sont: la lymphadénectomie lombo-aortique extrapéritonéale par LESS est faisable. Nous en avons décrit et codifié la technique pour la première fois par une incision iliaque gauche unique ; cette technique que nous avons mise au point est sure, reproductible et équivalente sur le plan carcinologique et ergonomique à la laparoscopie conventionnelle ; la lymphadénectomie lombo-aortique de staging est indispensable dans les LACC compte tenu du taux de faux négatif du TEP-TDM retrouvé dans ce travail de thèse (12% s'élevant à 22 % en cas de fixations ganglionnaires pelviennes suspectes). Nous avons également démontré sur la plus large de la série de littérature que la lymphadénectomie lombo-aortique associée à l'extension des champs d'irradiation en lombo-aortique lors de la radio-chimiothérapie apporte aux patientes présentant des micrométastases une survie identique à celle des patientes négatives histologiquement au niveau lombo-aortique. En revanche, en cas d'atteinte macrométastatique le pronostic demeure péjoratif et nécessite de proposer d'autres options thérapeutiques / In locally advanced cervical cancer (LACC) the most important predictor of disease recurrence is para-aortic nodal status. The aim of our thesis was to evaluate the role of para-aortic lymphadenectomy (the current gold standard to assess para-aortic nodal status) in the era of positron emission tomography (PET) and single incision surgery (LESS). The published results of this thesis are: extraperitoneal para-aortic lymphadenectomy by LESS is feasible and we have described and codified the technique for the first time by a single left iliac incision; the technique we have developed is safe, reproducible and oncologically and ergonomically equivalent to conventional laparoscopy; para-aortic LAD staging is essential in LACC given the false negative rate of PET-CT found in this work (12% increasing to 22% if PET-CT reveals suspicious pelvic lymph nodes). We have also demonstrated, in the largest case series published to date, that para-aortic lymphadenectomy followed by chemoradiation including the pelvis and para-aortic lymph nodes for patients with micrometastatic para-aortic nodal involvement provides an overall survival that is identical to the overall survival of LACC with histologically negative para-aortic lymph nodes. However, in case of macrometastatic disease prognosis remains pejorative and requires other treatment options