Thesis (M.S.)--Rochester Institute of Technology, 1994. / Typescript. Bibliography: leaves 97-101.

This thesis presents an investigation of pH-responsive, redox-sensitive poly(MMA-co- MAA) and poly(EA-co-MAA) hollow particles for the repair of load-bearing soft tissues, such as articular cartilage and the intervertebral disc. Hollow particles continue to attract major interest due to their numerous potential applications. The new method for hollow particle preparation presented in this thesis does not require the use of a colloidal template and is well suited for scaling up. Hollow particles were formed using linear poly(MMA-co-MAA) and poly(EA-co-MAA) aliphatic copolymers synthesised using free-radical chain copolymerisation performed in solution. These copolymers were dissolved in dichloromethane using methanol as a cosolvent and emulsified in water. Diffusion of the methanol into the aqueous phase prompts precipitation of the copolymer at the droplet/water interface. The more hydrophobic copolymers containing less MAA showed improved morphology compared to copolymers containing more MAA. Also, poly(EA-co-MAA) hollow particles had a more spherical morphology than poly(MMA-co-MAA) hollow particles with equivalent MAA contents. This was attributed to the lower Tg of the EA structural monomer, which resulted in more flexible particle shells. Unusually, during potentiometric titration of uncrosslinked hollow particles, the pH of the system decreased with increasing neutralisation. This behaviour is thought to be due to the unfolding of copolymer chains, exposing shielded carboxyl groups. The random structure of the copolymers is believed to be necessary for this behaviour. Crosslinked particles became swollen when the pH was increased using buffers. Concentrated dispersions formed self supporting gels, due to steric confinement, at 5 wt.%. The crosslinking process was performed by functionalising with cystamine using carbodiimide chemistry. This introduced disulphide crosslinks; which could be cleaved under reducing conditions at high pH, dissolving the gels. This ability to reduce the hollow particle shells to their constituent linear copolymer chains gives potential for natural removal from the body via extraction by the renal system. pH-triggered loading and release of a hydrophilic dye using crosslinked hollow particles was demonstrated. The similarity of the particle formation process to traditional solvent evaporation also allowed the loading of a hydrophobic dye. However, these particles were not crosslinked so release following swelling could not be investigated. Cystamine-crosslinked systems suffered from degradation due to thiol-disulphide exchange at high pH (~ pH 8). Crosslinking of one system was performed using 2-amino ethyl methacrylate (AEM). This introduced covalent, vinyl intra-shell crosslinking; which did not break down at high pH. Additional AEM was also used to allow inter-particle UVcrosslinking to form doubly crosslinked (DX) hollow-particle hydrogels. These gels did not re-disperse in buffer. To our knowledge, this is the first example of a covalent hydrogel formed from pH-responsive hollow particles. The DX gels offer improved mechanical properties compared to the singly crosslinked, physical gels. Freeze-dried samples of all of the gels produced during this study showed highly porous structures when observed using SEM. The rapid diffusion of FITC-dextran through a sample of DX gel indicates that these pores were interconnected. This is beneficial as it encourages tissue ingrowth, in addition to allowing the rapid diffusion of nutrients, oxygen and cell waste in vivo.

Methicillin-resistant Staphylococcus aureus (MRSA) is a pandemic human pathogen accounting for most of health-care associated infections throughout the world. However, in recent years, a more virulent strain of MRSA has emerged in the community defined as community-associated MRSA (CA-MRSA). These emerging strains of CA-MRSA are described to have different antibiotic susceptibility profiles, possess the SCCmec type IV element and usually produce the Panton-Valentine leukocidin (PVL) toxin. The majority of these CA-MRSA strains are associated with skin and soft tissue infections and necrotising pneumonia, with a 34% mortality rate. Identification and characterisation of MRSA isolates is mainly performed using phenotypic methods, which are time consuming. Little information exists on the prevalence and characteristics of MRSA isolates including antibiotic susceptibility patterns, PVL-producing CAMRSA strains, the SCCmec types and genotypes that might be circulating in the Steve Biko Academic Hospital. Identification and characterisation of MRSA isolates based on these criteria are important in controlling possible outbreaks in the clinical setting. In this study, 97 clinical MRSA isolates from the Steve Biko Academic Hospital, South Africa were collected between April 2006 to February 2007. These isolates were analysed and characterised using multiplex PCR (M-PCR), real-time PCR as well as staphylococcal protein A (spa) and hyper-variable region (HVR) typing. The aim of this study was to determine the antibiotic profiles, prevalence of MRSA isolates, the SCCmec types and the genotypes. Antibiotic susceptibility determination was performed using the disk diffusion susceptibility method as guidelined by the CLSI. Six distinct antibiotypes were identified with a total of 73%, 71%, 70% and 7% of MRSA isolates resistant to clindamycin, erythromycin, gentamicin and fusidic acid, respectively. The presence of Staphylococcus aureus specific 16S rRNA, the mecA and PVL genes was determined using a modified M-PCR assay. A total of 4% of the MRSA isolates possessed the PVL gene. Real-time PCR analysis also showed a 100% prevalence of the PVL gene in the same 4% MRSA isolates confirming the results of the first M-PCR assay. The second M-PCR was used to determine the SCCmec type prevalence and to distinguish between health-care associated MRSA (HA-MRSA) and CA-MRSA. SCCmec typing showed 67% of the isolates belonged to SCCmec type II and 14.4% SCCmec type III, both types belonging to HA-MRSA. A total of 4% of the MRSA isolates were CA-MRSA belonging to SCCmec type IVd. Genotyping results showed three distinct spa clusters whilst HVR showed six distinct clusters. Molecular-based assays proved to be useful tools to determine the prevalence and monitoring of MRSA outbreaks as well as to identify the SCCmec types, subtypes and genotypes of MRSA strains that might be circulating in the hospital. The determination of the different antibiotypes of MRSA can assist in the monitoring of the antibiotic resistant profile trends in the Steve Biko Academic Hospital, thus assisting with the correct implementation of antibiotic regimens for suspected MRSA infections. In an endeavour to assess the dissemination of MRSA strains especially PVL expressing CA-MRSA strains, it is of paramount importance to continuously monitor the emergence of these strains in clinical settings. Copyright / Dissertation (MSc)--University of Pretoria, 2010. / Medical Microbiology / unrestricted

Being able to accurately model soft tissue behaviour, such as that of heart valvular tissue, is essential for developing effective numerical simulations of in-vivo conditions and determining patient-specific care options. Although several analytical material models, based on strain energy functions, have been successful in predicting soft tissue behaviour, complications arise when these models are implemented into finite element (FE) programs due to the incorporation of a penalty parameter for numerically enforcing material incompressibility. Specifically, material parameters determined through non-FE methods may no longer produce a material behaviour that reflects the experimental behaviour once they are used in an FE analysis. Based on commercial finite element software LS-DYNA, an inverse methodology was developed in MATLAB to simultaneously optimize the material parameters and the penalty parameter for the Guccione strain energy model. The methodology produced accurate predictions of the material behaviour under planar equibiaxial testing for five biomaterials used in heart valve cusp replacements.

Class of 2017 Abstract / Objectives: To assess the cost-effectiveness of vancomycin, daptomycin, linezolid, oritavancin, and telavancin as empiric treatment for MRSA skin and soft tissue infections in an inpatient setting from a third party perspective. Methods: A decision analytic tree model was constructed using TreeAge Pro and utilizing efficacy data from published clinical trials and costs estimates using HCUPnet.gov and Micromedex’s RedBook. Sensitivity analyses were run on linezolid costs, as well as oritavancin’s costs and efficacy data. Results: Linezolid was the most cost effective medication, dominating all other therapies. In a sensitivity analysis, increasing linezolid’s cost to include 7 days of inpatient therapy did not result in other therapies no longer being dominated. In two other sensitivity analyses, oritavancin was no longer dominated at 91.8% efficacy, but was still dominated with only 3 days of inpatient therapy. Conclusions: Linezolid was the most cost effective therapy for empiric treatment of suspected MRSA skin and soft tissue infections requiring hospitalization from a third party perspective.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13158号 / 論医博第2145号 / 新制||医||1029(附属図書館) / (主査)教授 川上 浩司, 教授 戸井 雅和, 教授 松田 秀一 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Book Summary: Serves the needs of advanced practice nurses because it’s written by nurse practitioners for nurse practitioners, in collaboration with a physician. Organizes content around the Circle of Caring framework for nursing-based knowledge and holistic care. Explores complementary and alternative treatments for each disorder. Covers the broadest range of human disease and disorders using a systems-based approach, presenting both common complaints and common problems to help students narrow down the possible differentials to the most likely diagnosis. Considers interactions of pharmaceuticals with alternative medications and nutraceuticals. Features coverage of pathophysiology and diagnostic reasoning as well as up-to-date guidance on laboratory and diagnostic tests. Emphasizes evidence-based practice with information on evidence levels and more references to primary studies. Integrates discussions of health policy and primary care throughout the text.

Yes / Background: Soft tissue sarcomas are heterogeneous and a major complication in their management is that the existing classification scheme is not definitive and is still evolving. Leiomyosarcomas, a major histologic category of soft tissue sarcomas, are malignant tumours displaying smooth muscle differentiation. Although defined as a single group, they exhibit a wide range of clinical behaviour. We aimed to carry out molecular classification to identify new molecular subgroups with clinical relevance. Methods: We used gene expression profiling on 20 extra-uterine leiomyosarcomas and cross-study analyses for molecular classification of leiomyosarcomas. Clinical significance of the subgroupings was investigated. Results: We have identified two distinct molecular subgroups of leiomyosarcomas. One group was characterised by high expression of 26 genes that included many genes from the sub-classification gene cluster proposed by Nielsen et al. These sub-classification genes include genes that have importance structurally, as well as in cell signalling. Notably, we found a statistically significant association of the subgroupings with tumour grade. Further refinement led to a group of 15 genes that could recapitulate the tumour subgroupings in our data set and in a second independent sarcoma set. Remarkably, cross-study analyses suggested that these molecular subgroups could be found in four independent data sets, providing strong support for their existence. Conclusions: Our study strongly supported the existence of distinct leiomyosarcoma molecular subgroups, which have clinical association with tumour grade. Our findings will aid in advancing the classification of leiomyosarcomas and lead to more individualised and better management of the disease. / Alexander Boag Sarcoma Fund.

Yes / Complex biological tissues are highly viscoelastic and dynamic. Efforts to repair or replace cartilage, tendon, muscle, and vasculature using materials that facilitate repair and regeneration have been ongoing for decades. However, materials that possess the mechanical, chemical and resorption characteristics necessary to recapitulate these tissues have been difficult to mimic using synthetic resorbable biomaterials. Herein, we report a series of resorbable elastomer-like materials that are compositionally identical and possess varying ratios of cis:trans double bonds in the backbone. These features afford concomitant control over the mechanical and surface eroding degradation properties of these materials. We show the materials can be functionalized post-polymerization with bioactive species and enhance cell adhesion. Furthermore, an in vivo rat model demonstrates that degradation and resorption are dependent on succinate stoichiometry in the elastomers and the results show limited inflammation highlighting their potential for use in soft tissue regeneration and drug delivery.