Thesis (PhD (Industrial Engineering))--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Back pain is a common concern amongst a growing population of people across the world today, where in most cases the pain can become unbearable resulting in major lifestyle adjustments. Seventy to eighty percent of the population of the Western world experiences low-back pain at one time or another. Pain can be produced as a worn disc becomes thin, narrowing the space between the vertebrae. Pieces of the damaged disc may also break off and cause irritation to the nerves signalling back pain. Depending on the severity of a patient’s condition, and after conservative treatment options have been exhausted, a disc replacement surgery (arthroplasty) procedure may be prescribed to restore spacing between vertebrae and relieve the pinched nerve, while still maintaining normal biomechanical movement. Typical complications that are however still observed in some cases of disc implants include: anterior migration of the disc, subsidence (sinking of disc) and lateral subluxation (partial dislocation of a joint). Issues such as function, correct placement and orientation, as well as secure fixation of such a disc implant to the adjacent vertebrae are highly important in order to replicate natural biomechanical behaviour and minimise the occurrence of the complications mentioned. As various imaging and manufacturing technologies have developed, the option for individual, patientspecific implants is becoming more of a practical reality than it has been in the past. The combination of CT images and Rapid Manufacturing for example is already being used successfully in producing custom implants for maxilla/facial and cranial reconstructive surgeries. There exists a need to formalise a process chain for the design and manufacture of custom-made intervertebral disc implants and to address the issues involved during each step. Therefore this study has investigated the steps involved for such a process chain and the sensible flow of information as well as the use of state-of-the-art manufacturing technologies. Strong emphasis was placed on automation of some of the processes as well as the user-friendliness of software where engineers and surgeons often need to work together during this multi-disciplinary environment. One of the main benefits for customization was also investigated, namely a reduction in the risk and potential for implant subsidence. Stiffness values from pressure tests on vertebrae were compared between customized implants and implants with flat endplate designs. Results indicated a statistically significant improvement of customized, endplate matching implants as opposed to flat implant endplates. Therefore it may be concluded that the use of customized intervertebral disc implants with patient specific endplate geometry may decrease the risk and potential for the occurrence of subsidence. / AFRIKAANSE OPSOMMING: Rugpyn is ‘n algemene bekommernis vir ‘n groeiende populasie van mense in die wêreld vandag, waar in meeste gevalle die pyn ondraagbaar kan raak en groot leefstyl aanpassings vereis. Sewentig tot tagtig persent van die populasie in die Westerse wêreld ondervind lae rugpyn op een of ander stadium. Die pyn kan veroorsaak word deur ‘n intervertebrale skyf wat verweer en dunner word, en veroorsaak dat die spasie tussen die vertebrae vernou. Stukkies van die beskadigde skyf mag ook afbreek en irritasie aan die senuwees veroorsaak wat verdere pyn kan veroorsaak. Afhangende van die ernstigheid van ‘n pasiënt se geval, en nadat opsies vir konservatiewe behandeling uitgeput is, kan ‘n skyf vervangings-prosedure (artroskopie) voorgeskryf word om die spasie tussen die vertebrae te herstel en sodoende die geknypte senuwee te verlos. Die skyf vervanging herstel spasiëring tussen vertebrae terwyl die normale biomeganiese beweging ook behoue bly, in teenstelling met ‘n fusieprosedure wat die betrokke vertebrae aanmekaar vasheg en normale beweging belemmer. Tipiese komplikasies wat egter steeds na ‘n skyf vervanging in sommige gevalle waargeneem word sluit in: anterior migrasie van die inplantaat, insinking, sowel as laterale sublukasie (gedeeltelike dislokasie van ‘n gewrig). Faktore soos funksie, korrekte posisionering en orientasie, sowel as vashegting van so ‘n skyf inplantaat tot die aanliggende vertebrale bene is besonder belangrik om natuurlike biomeganiese beweging te herstel en sodoende bogenoemde komplikasies te verminder. Soos wat verskeie beeldings- en vervaardigingstegnologië verbeter het oor die laaste dekade, het die moontlikheid vir individuele, pasiënt-spesifieke inplantate al hoe meer ‘n praktiese realiteit begin word. Die kombinasie van Gerekenariseerde Tomografie (GT), tesame met Snel Vervaardiging word byvoorbeeld reeds suksesvol aangewend tydens die ontwerp en vervaardiging van pasiënt-spesifieke inplantate vir maksilla- en kraniale rekonstruktiewe chirurgie. Daar bestaan egter ‘n behoefte om ‘n formele prosesketting vir die ontwerp en vervaardiging van pasiënt-spesifieke intervertebrale skyf inplantate te ontwikkel en om belangrike faktore tydens elke stap noukeurig te beskryf. Hierdie studie het na die verskillende stappe in die prosesketting gekyk om ‘n sinvolle vloei van informasie en benutting van hoë gehalte vervaardigingstegnologië saam te snoer. Sterk klem was gelê op outomatisering van prosesse asook gebruikersvriendelikheid van sagteware waar ingenieurs en medici dikwels saam moet werk tydens hierdie kruisdissiplinêre omgewing. Een van die hoof verwagte voordele met die gebruik van pasklaar skyf inplantate, naamlik die vermindering van moontlike insinking van die inplantaat in die been, is ook ondersoek. Die ondersoek het druktoetse behels en die vergelyking van ooreenstemmende styfheid tussen inplantate wat die kontoer van die bene volg teenoor gewone plat eindplate. Die resultate was statisties beduidend in die guns van die pasklaar inplantate wat die beenkontoere gevolg het, en bewys dus dat die risiko vir insinking verminder is.

<p>Schwann cells (SCs) are PNS glia with numerous neuron-supporting functions, including myelination of axons. Although lesser discussed, SCs also fulfill many important roles after peripheral nerve injury (PNI) contributing significantly to the PNS regeneration process. Clusters of congregated SCs (Bands of Bungner) precede axon regeneration and facilitate the growth of extending axons to their distal targets which is particularly important in the lesion area of severed nerves. While this phenomenon occurs naturally, recovery from PNI can still be inadequate, especially in nerve transection or large gap injuries. Current treatments for nerve transection injuries are limited to coaptation of the nerve via sutures or nerve grafts. However, poor functional outcomes or donor site morbidity remain unaddressed problems. At the cellular level, axon pathfinding and extension relies heavily on the interaction between SCs and axonal growth cones. Depletion or removal of SCs at the lesion has been implicated to poor functional outcomes. With their pivotal role throughout nerve regeneration, we theorize axon regeneration can be improved by augmenting the SC population at the site of injury by encouraging migration to the lesion and via expression of morphological phenotypes that imitate the Bands of Bungner. </p> <p>DC electric fields (EFs) have been well studied in the past as a method to modulate cell orientation and migration and within the context of the nervous system, have been used to promote regeneration in lesioned spinal cords. However, very little work has investigated the effects of electrical stimulation on glia, such as SCs. Existing literature is lacking with regards to various aspects of SC responses, including direction of alignment. We hypothesize electrical stimulation can modulate SC behavior to reinforce/replicate behaviors observed within Bands of Bungner, which may be developed into a treatment for victims suffering peripheral nerve injury. </p> <p>We begin the current study with a thorough investigation into electric field modulated SC behavior. Using conventional 2D cell culture we demonstrate SC sensitivity to EFs by analyzing alignment, morphology and migration data. We employed EFs within the physiologic range. Waveforms used were constant DC as well as a 50% duty cycle DC and an oscillating DC. The latter two may prove more appropriate <i>in vivo</i> due to reduced accumulation of cytotoxic byproducts generated at the electrode interfaces. </p> <p>Our results highlight the sensitivity of SCs to DC electric fields of varying waveforms. SCs showed a strong propensity to align perpendicular to the field and display some cathodal migration in 2D cultures. Additional studies with variable cell density revealed cell-cell interaction further enhanced the alignment response. To more closely replicate the nerve microenvironment, a 3D cell culture model of PNI was created. Embedded in matrices, we found SCs displayed weaker migratory and alignment responses compared to 2D results. The direction of galvanotaxis was reversed, with SCs migrating toward the anode. Both alignment and migratory responses have potential applications for PNI. The galvanotactic behavior of SCs could be used to boost the SC population, increasing the number of Bands of Bungner. Cell alignment would be particularly advantageous at the lesion where axon regeneration is most difficult without the physical guidance of endoneurial tubes.</p> <p>This study characterizes SC behavior in applied EFs using conventional 2D and 3D cell culture techniques. We found SCs are sensitive to electric stimulation, supporting the idea that applied EFs could be used to indirectly promote regeneration in damaged peripheral nerve by modulating SC response after injury. Potential applications include generating an EF across damaged nerves to align SCs, especially in the lesioned area, using EFs to induce SC migration to the lesion to increase the number of cells guiding severed axons, and pre-aligning SCs in synthetic nerve grafts.</p>

Com a redução das barreiras tarifárias ao comércio internacional, as normas técnicas, regulamentos técnicos e procedimentos de avaliação da conformidade vêm se tornando importantes mecanismos protecionistas e de restrição ao comércio. Esse trabalho tem por objetivo estudar essas questões, tendo como foco principal a exportação para a União Européia dos equipamentos eletromédicos produzidos por pequenas e médias empresas brasileiras. Realiza-se uma revisão bibliográfica buscando-se identificar e comparar as normas técnicas, os regulamentos técnicos e os mecanismos de avaliação da conformidade para os dispositivos eletromédicos, praticados pela União Européia e os vigentes no Brasil. É desenvolvida uma pesquisa junto a PMEs Pequenas e Médias Empresas fabricantes de dispositivos eletromédicos e exportadores para a União Européia, buscando-se identificar as dificuldades encontradas, as formas de superação dessas e os apoios recebidos. É elaborado um método, baseado nas experiências estudadas e adquiridas a partir da pesquisa junto às PMEs, para a identificação e superação das dificuldades técnicas para a exportação dos equipamentos eletromédicos para a União Européia. Conclui-se que não existem propriamente barreiras técnicas e que as dificuldades enfrentadas pelas empresas podem ser superadas com a participação nos fóruns de normalização, apoio técnico dos institutos tecnológicos, apoio financeiro das agências governamentais de fomento e investimentos em pesquisa, desenvolvimento e inovação. / With the reduction of the tariff barriers to international trade, the technical standards, technical regulations and conformity assessment proceedings are becoming important protectionist and trade restriction mechanisms. This work aims to study these questions, focusing mainly the case of medical devices produced by the small and medium Brazilians companies and exported to European Union. A bibliography revision is done to identify and to compare the technical standards, technical regulations and conformity assessment proceedings for the medical devices, in European Union and Brazil. A survey is developed with the small and medium producers and exporters of medical devices, searching the difficulties, ways of overcoming them, and the support obtained. A method is proposed to identify and overcome the technical difficulties to export medical devices to European Union, based on the experiences studied and obtained from the small and medium producers. The conclusion is that there are no technical barriers and the difficulties faced by the producers can be overcome through the participation in standardization forum, the technical support of the technological institutes, the financial support of the governmental promotion agencies, and investment in research, development and innovation.

Avec une population mondiale vieillissante, de plus en plus de personnes sont à risque de présenter des pathologies pour lesquelles l’Imagerie par Résonance Magnétique (IRM) est une modalité de choix : ainsi, le nombre d’examens IRM est en constante augmentation. Les patients âgés étant par ailleurs une population davantage susceptible de recevoir une implantation de dispositifs médicaux (tels qu’un pacemaker ou une prothèse de hanche), la sécurité des patients implantés en IRM est primordiale. En effet, cet appareil d’imagerie médicale fait intervenir différents champs électromagnétiques pouvant interagir avec un implant métallique et donner lieu à des risques potentiels pour le patient. Si des normes de compatibilité existent aujourd’hui pour soumettre individuellement les dispositifs médicaux à des tests standardisés et assurer leur innocuité en environnement IRM, les interactions entre multiples dispositifs médicaux vis-à-vis des ondes électromagnétiques radiofréquence (et des dangers qui peuvent en résulter) sont un domaine complexe qu’il est nécessaire de comprendre. L’objet de cette thèse est d’étudier ces interactions sur plusieurs niveaux : interactions intra-dispositif, interactions inter-dispositifs et interactions entre dispositif et plusieurs antennes. Une méthode de prédiction d’échauffement a été proposée pour simplifier l’étude de larges gammes d’implants, suivant les variations de paramètres caractérisant les différentes parties au sein d’une prothèse. Des simulations électromagnétiques et thermiques, associées à des mesures expérimentales dans un environnement IRM clinique, ont permis de mettre en évidence des phénomènes de couplages entre deux implants simplifiés et d’introduire une nouvelle métrique pour les quantifier. Enfin, une étude multi-antennes a fourni des éléments de réponse à la question de la sécurité d’un patient implanté en présence de plusieurs antennes, dans une configuration semblable à celle des examens en routine clinique. Les travaux présentés dans cette thèse ont ainsi permis d’évaluer les interactions vis-à-vis de la radiofréquence de l’IRM en présence d’un ou plusieurs dispositifs médicaux et antennes, ouvrant plusieurs perspectives pour aller vers une IRM sûre pour tous / With an aging population worldwide, more and more persons are at risk of suffering from pathologies which are best diagnosed or monitored with Magnetic Resonance Imaging (MRI): thus, the number of MRI exams is constantly increasing. Moreover, elderly patients being likely to undergo a medical device implantation (such as a pacemaker or a hip prosthesis) the safety of implanted patient in MRI is crucial. The medical imaging technique involves indeed different electromagnetic fields which can interact with a metallic implant and lead to potential hazard for the patient. Even though compatibility guidelines exist today to subject individually medical devices to standardized tests and ensure their harmlessness in an MRI environment, the interactions between multiple medical devices with respect to radiofrequency electromagnetic waves (and to the hazards that may follow) are a complex research area that has to be understood. The aim of this thesis is to study these interactions on different levels: intra-device interactions, inter-devices interactions and interactions between a device and several antennas. A prediction method has been proposed to simplify the study of large range of implants, according to the variations of parameters characterizing the different parts of a prosthesis. Electromagnetic and thermal simulations, associated with experimental measurements in a clinical MRI environment, allowed to highlight a coupling phenomenon between two simplified implants and to introduce a new metric to quantify them. Finally, a multi-antenna study led to some insights to answer the question of the safety of an implanted patient with several antennas, in a configuration similar to a clinical routine exam. Thus, the research work presented in this thesis allowed to assess the interactions with respect to MRI radiofrequency in presence of one or several medical devices and antennas, opening new prospects towards a safe MRI for everyone

A água exerce papel fundamental nas diferentes fases do processo de fabricação de artigos para saúde (médico-hospitalares, farmacêuticos, e clínicos), exigindo elevado grau de pureza, que certifique a sua inocuidade. Portanto, se faz necessário maior controle dos sistemas de purificação de água e suas etapas de tratamento, onde a formação de biofilmes pode contaminar os artigos para saúde e, consequentemente, causar injúria a pacientes submetidos à aplicação dos mesmos. Embora os artigos médicos sejam esterilizados por óxido de etileno (ETO), seu processo de manufatura deve prever o mínimo acréscimo possível de contaminantes. Considerando que a água purificada e a esterilização dos artigos para saúde são fatores determinantes para o sucesso de sua aplicação, este trabalho foi dividido em duas partes distintas. A primeira parte aborda o controle das etapas de purificação da água, que é destinada à lavagem de componentes termoplásticos, que são utilizados na fabricação de artigos para saúde. Os níveis máximos de carga microbiana (expressos em ciclos de log10 UFC/100mL) encontrados ao longo do sistema de purificação de água foram: 3,48 log10 na água de entrada; 3,57 log10 nos filtros multimeios; 3,75 log10 nos abrandadores; 4,97 log10 no filtro de carvão ativado; 2,53 log10 na osmose reversa; 2,70 log10 no tanque de estocagem e distribuição; 2,56 log10 na lâmpada ultravioleta; 2,53 log10 nos filtros 0,05 &#181;m; 1,98 log10 nos pontos de uso. Flavimonas oryzihabitans e Micrococcus luteus foram as bactérias Gram-negativa e Grampositiva, respectivamente, isoladas e identificadas com maior freqüência na água, em diferentes estágios do sistema, inclusive após a passagem dessa através das membranas de osmose reversa. A segunda parte do estudo teve como objetivo determinar o tempo de aeração necessário para que os oxigenadores de sangue e conjuntos de tubos de PVC, após esterilização por ETO, permaneçam em aeração, para dissipação dos resíduos de ETO. Avaliou-se também a potencialidade da proteína verde fluorescente (GFP) como biossensor no processo de esterilização. O processo de esterilização destes artigos médicos foi monitorado com indicadores biológicos Bacillus atrophaeus, proteína verde fluorescente (GFP) e controles de temperatura, pressão e umidade em ciclos de 2 h (ciclo curto), 4 h (meio ciclo) e 8 h (ciclo longo). As curvas de dissipação, determinadas por cromatografia gasosa, confirmaram níveis residuais menores que 25 ppm para ETO e etileno cloridrina (EC); e inferiores a 250 ppm para etileno glicol (EG), ao final do processo de esterilização para os oxigenadores; e, após 221 horas de aeração, para os conjuntos de tubos de PVC. Nos ciclos de esterilização, as reduções na intensidade de fluorescência da GFP ocorreram em função do tempo de exposição ao ETO; enquanto germinação de esporos e/ou crescimento de B. atrophaeus não foi observado. / The water exerts important paper in different phases of critical items manufacture in the health care units, pharmaceutical industries, hospitals and clinics, becoming necessary a rigorous control of the water purification systems, storage and distribution, in order to prevent biofilms formation and cross-contamination between devices and patients, who are submitted to critical articles and parenteral solution application. The sterilization of critical devices by ethylene oxide (ETO) should predict minimum addition of possible contaminants and residues. Considering that the purified water and the sterilization are crucial factors for medical devices, this work was divided in two parts. The first part evaluated continuously the stages of the system for the purification of the water, which purity level is critical and determines the quality of the washing of thermoplastic components used in the manufacture of critical items. The maximum levels of heterotrophic load (log10 UFC/100mL) found throughout the water purification system were: 3.48 log10 in the water inlet; 3.57 log10 in the multimedium filters; 3.75 log10 in the softeners; 4.97 log10 in the activated carbon filter; 2.53 log10 in the reverse osmosis; 2.70 log10 in the tank of storage and distribution; 2.56 log10 in the UV lamp; 2.53 log10 in the 0.05&#181;m filters; 1.98 log10 in the consumption points. Flavimonas oryzihabitans and Micrococcus luteus were the main Gram-negative and Grampositive bacteria, respectively found in the purified water after reverse osmosis. The second part of this study had as objective the determination of the needed aeration time for blood oxygenators and sets of PVC tubing must be kept in aeration room for dissipation of ETO residues; and also evaluated the possibility of GFP as biosensor. ETO is used as in a mixture (10% ETO and 90% CO2). Residual levels of ETO and its derivatives, ethylene chloridrin (ECH) and ethylene glycol (EG), which remain in these devices, must be controlled to prevent serious injuries to the patients. The sterilization process of the oxygenators and sets of PVC tubing was monitored with Bacillus atrophaeus and fluorescent green protein (GFP). The temperature, pressure and humidity were controlled in the sterilization cycles of 2 h (short cycle), 4 h (half cycle) and 8 h (long cycle). The dissipation curves of the residues were determined by gaseous chromatography and the residual concentrations were lower than 25 ppm of ETO and ECH and lower than 250 ppm of EG immediately after the sterilization processes for oxygenators and after 221 hours of aeration for the sets of PVC tubing. Reductions in the fluorescence intensity of GFP were observed as a function of the exposition time to the ETO. No growth of B. atrophaeus spores was observed after cycles.

Un des enjeux sociétal important concerne le vieillissement des personnes en situation de handicap mental. L’allongement de l’espérance de leur vie a pour conséquence que les établissements spécialisés pour l’accueil des personnes âgées (comme les EPHAD) se retrouvent à accueillir des personnes souffrant des maladies du vieillissement (démence par exemple) en plus d’un handicap mental. Se pose alors le problème de l’accès aux soins pour cette population à travers l’usage des dispositifs médicaux adaptés aux caractéristiques des personnes âgées.  La présence d’un handicap mental a plusieurs conséquences : difficulté de compréhension des usages des dispositifs médicaux, personnels peu formés aux conséquences de cette handicap). En effet, les dispositifs médicaux sont spécifiques soit pour les situations de handicaps ou soit pour le contexte du vieillissement (avec des normes, des règles de remboursement différents). Que se passe t-il dans le cas d’un dispositif médical qui doit être adapté non seulement aux contraintes dues au vieillissement et à celles dues à un handicap mental ? Nous proposons donc de partir des questions de départ suivantes comme objectif pour ce sujet de thèse : Y a t-il des difficultés d'accès aux soins pour les personnes âgées en situation de handicap? Quels sont les manques exprimés par les usagers eux-mêmes et par les professionnels du sanitaire? Quel Dispositif Médical faudrait-il "améliorer" ou créer pour faciliter l'accès aux soins pour cette population spécifique ? / One og the biggest challenge for our societies is the aging of the population. One is getting particularly important : the ageing of people with mental disorder. The increase of their life expectancy has several consequences in their access to care. Establishment which are specialized in the welcolme of elderly people are now welcoming people with mental disorder. The access to care is one of the most problematic aspect in this phenomenum : what medical devices are adapted for this new population ? Indeed, medical devices are adapted either for people with mental disorder, either for elderly people. For people with mental disorder getting older, there is a need to adapt the tools for them, to adapt the way of communicating with them and the way to monitore them. We are trying to propose new solutions to answer all these questions.

A água exerce papel fundamental nas diferentes fases do processo de fabricação de artigos para saúde (médico-hospitalares, farmacêuticos, e clínicos), exigindo elevado grau de pureza, que certifique a sua inocuidade. Portanto, se faz necessário maior controle dos sistemas de purificação de água e suas etapas de tratamento, onde a formação de biofilmes pode contaminar os artigos para saúde e, consequentemente, causar injúria a pacientes submetidos à aplicação dos mesmos. Embora os artigos médicos sejam esterilizados por óxido de etileno (ETO), seu processo de manufatura deve prever o mínimo acréscimo possível de contaminantes. Considerando que a água purificada e a esterilização dos artigos para saúde são fatores determinantes para o sucesso de sua aplicação, este trabalho foi dividido em duas partes distintas. A primeira parte aborda o controle das etapas de purificação da água, que é destinada à lavagem de componentes termoplásticos, que são utilizados na fabricação de artigos para saúde. Os níveis máximos de carga microbiana (expressos em ciclos de log10 UFC/100mL) encontrados ao longo do sistema de purificação de água foram: 3,48 log10 na água de entrada; 3,57 log10 nos filtros multimeios; 3,75 log10 nos abrandadores; 4,97 log10 no filtro de carvão ativado; 2,53 log10 na osmose reversa; 2,70 log10 no tanque de estocagem e distribuição; 2,56 log10 na lâmpada ultravioleta; 2,53 log10 nos filtros 0,05 &#181;m; 1,98 log10 nos pontos de uso. Flavimonas oryzihabitans e Micrococcus luteus foram as bactérias Gram-negativa e Grampositiva, respectivamente, isoladas e identificadas com maior freqüência na água, em diferentes estágios do sistema, inclusive após a passagem dessa através das membranas de osmose reversa. A segunda parte do estudo teve como objetivo determinar o tempo de aeração necessário para que os oxigenadores de sangue e conjuntos de tubos de PVC, após esterilização por ETO, permaneçam em aeração, para dissipação dos resíduos de ETO. Avaliou-se também a potencialidade da proteína verde fluorescente (GFP) como biossensor no processo de esterilização. O processo de esterilização destes artigos médicos foi monitorado com indicadores biológicos Bacillus atrophaeus, proteína verde fluorescente (GFP) e controles de temperatura, pressão e umidade em ciclos de 2 h (ciclo curto), 4 h (meio ciclo) e 8 h (ciclo longo). As curvas de dissipação, determinadas por cromatografia gasosa, confirmaram níveis residuais menores que 25 ppm para ETO e etileno cloridrina (EC); e inferiores a 250 ppm para etileno glicol (EG), ao final do processo de esterilização para os oxigenadores; e, após 221 horas de aeração, para os conjuntos de tubos de PVC. Nos ciclos de esterilização, as reduções na intensidade de fluorescência da GFP ocorreram em função do tempo de exposição ao ETO; enquanto germinação de esporos e/ou crescimento de B. atrophaeus não foi observado. / The water exerts important paper in different phases of critical items manufacture in the health care units, pharmaceutical industries, hospitals and clinics, becoming necessary a rigorous control of the water purification systems, storage and distribution, in order to prevent biofilms formation and cross-contamination between devices and patients, who are submitted to critical articles and parenteral solution application. The sterilization of critical devices by ethylene oxide (ETO) should predict minimum addition of possible contaminants and residues. Considering that the purified water and the sterilization are crucial factors for medical devices, this work was divided in two parts. The first part evaluated continuously the stages of the system for the purification of the water, which purity level is critical and determines the quality of the washing of thermoplastic components used in the manufacture of critical items. The maximum levels of heterotrophic load (log10 UFC/100mL) found throughout the water purification system were: 3.48 log10 in the water inlet; 3.57 log10 in the multimedium filters; 3.75 log10 in the softeners; 4.97 log10 in the activated carbon filter; 2.53 log10 in the reverse osmosis; 2.70 log10 in the tank of storage and distribution; 2.56 log10 in the UV lamp; 2.53 log10 in the 0.05&#181;m filters; 1.98 log10 in the consumption points. Flavimonas oryzihabitans and Micrococcus luteus were the main Gram-negative and Grampositive bacteria, respectively found in the purified water after reverse osmosis. The second part of this study had as objective the determination of the needed aeration time for blood oxygenators and sets of PVC tubing must be kept in aeration room for dissipation of ETO residues; and also evaluated the possibility of GFP as biosensor. ETO is used as in a mixture (10% ETO and 90% CO2). Residual levels of ETO and its derivatives, ethylene chloridrin (ECH) and ethylene glycol (EG), which remain in these devices, must be controlled to prevent serious injuries to the patients. The sterilization process of the oxygenators and sets of PVC tubing was monitored with Bacillus atrophaeus and fluorescent green protein (GFP). The temperature, pressure and humidity were controlled in the sterilization cycles of 2 h (short cycle), 4 h (half cycle) and 8 h (long cycle). The dissipation curves of the residues were determined by gaseous chromatography and the residual concentrations were lower than 25 ppm of ETO and ECH and lower than 250 ppm of EG immediately after the sterilization processes for oxygenators and after 221 hours of aeration for the sets of PVC tubing. Reductions in the fluorescence intensity of GFP were observed as a function of the exposition time to the ETO. No growth of B. atrophaeus spores was observed after cycles.

L'assurance qualité est une discipline récente dans le domaine médical, d'autant plus en odontologie. Sa mise en oeuvre passe dans notre discipline essentiellement par l'application de règles d'exigences vis-à-vis des dispositifs médicaux utilisés au sein des cabinets dentaires. Les implants, les piliers, les prothèses implantaires mais également les guides chirurgicaux sont des exemples appliqués au domaine implantaire. Cette technique chirurgico-prothétique se doit d'être exécutée dans les meilleurs conditions avec une exigence optimale : chaque acte pouvant avoir des conséquences sur le patient et/ou l'avenir du traitement. Afin de répondre aux exigences d'assurance qualité du traitement implantaire, il semble que les guides chirurgicaux statiques puissent être un moyen afin d'améliorer le placement implantaire impactant donc la qualité de la thérapeutique mise en place. Dans un premier temps, les notions d'assurance qualité et des dispositifs médicaux sont remis en lumière, notamment au travers du filtre de l'implantologie orale. Ensuite, la qualité du traitement implantaire est discutée : des bases historiques jusqu'aux connaissances d'aujourd'hui. Il est important de maitriser l'évolution de cette technique et des outils associées afin de comprendre et donc d'utiliser les outils diagnostics et thérapeutiques à notre disposition aujourd'hui. Le dernier temps de ce travail constitue l'évaluation des outils actuels en implantologie (CFAO, stéréolithographie, chirurgie guide statique, informatique) au travers d'une étude sur sujets anatomiques. Cette étude évalue la précision du positionnement implantaire avec des guides dits conventionnels et des guides de chirurgie guidée statique. Cette précision est évaluée par comparaison des images préalables de planification et des examens tridimensionnels post-opératoires / The quality assurance is a recent discipline in the medical domain, all the more in odontology. Its implementation passes in our discipline essentially by the application of rules of requirements towards medical devices used within dental surgeries. Implants, abutments, implant’s prosthesis but also the surgical guides are examples applied to the domain. This surgico-prosthetic technique owes be executed in the best conditions with an optimal requirement: every act which can have consequences on the patient and/or the future of the treatment. To meet the requirements of quality assurance of the treatment, it seems that the static surgical guides can be a way to improve the placement of implants thus impacting on the quality of the organized therapeutics. At first, the notions of quality assurance and medical devices are handed in light, in particular through the filter of the oral implantology. Then, the quality of the treatment is discussed: historic bases until the knowledge of today. It is important to master the evolution of this technique and tools associated to understand and thus use tools diagnoses and therapeutic at our disposal today. The last time of this work establishes) the evaluation of the current tools implantologie (CAD-CAM, stereolithography, surgery guides static, IT) through a study on anatomical subjects. This study estimates the precision of the implant’s positioning with conventional said guides and guides of static guided surgery. This precision is estimated by comparison of the preliminary images of planning and the post operative threedimensional examinations

<p>Medical devices are becoming more important in the health care sector. One of the major issues for companies developing and producing medical devices is to be updated on the regulatory requirements and implement them in the process. This thesis examines the regulatory requirements for medical devices in Argentina, Australia, Brazil, Canada, India, Japan, Mexico, Russia, South Korea and Taiwan and compares them with the requirements in the European Union.</p><p>The conclusion of this thesis is that most countries have similar requirements for registration of medical devices and are striving to harmonize with the GHTF guidelines. A company goes far by following the requirements in EU, USA or the GHTF guidelines.</p>

In recent years, many Personal Health Record (PHR) systems have been developed to retrieve patients&rsquo / Electonic Health Records (EHRs) from external sources. However, current PHRs can provide access to only a small number of EHR systems, since there are many dierent interfaces, data formats and medical terminologies among dierent systems. When this is the case, all these diversity yields high integration costs. Development of such systems is dicult and expensive because of the reasons such as accessing to evidence based medical information, utilization of social networks to share information, incorporation of available medical knowledge models, etc. Due to the technical diversity of external information systems, a developer of a PHR system faces a dicult integration process when he wants to integrate a new source or service. Integration of medical devices is also important and necessary in a PHR system. However, most of the medical device vendors use proprietary formats and protocols for communicating their devices with external systems / again, causing high integration eorts and costs. In this thesis, these problems and challenges are addressed by providing an on-line personal iv healthcare management platform, i.e. eSaglikKaydim which is built on top of a highly modular architecture and provides services based on worldwide standards. In this way, eSaglikKaydim platform can be integrated with any external health information service and medical device so that it maximizes the data variety retrieved from all kinds of external health data sources. The work presented in this thesis is part of the OSAmI project supported by European ITEA and funded by the TU&uml / BI