No description available.

No description available.

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

The skin-implant interface of percutaneous devices is generally weak and can fail when excessive loading disrupts the sealing of the interface by dermal and epidermal cells and tissue. As such, the formation of a stable implant-skin junction is a major factor in determining percutaneous implant success. In this study, we used functionalized self-assembled monolayers (SAMs) with discrete surface properties as model systems to assess the effects of biomaterial surface properties on controlling fibronectin (FN) adsorption and keratinocyte spreading and adhesion. The surface properties investigated were charge (positive and negative) and wettability (hydrophobic and hydrophilic). Gold slides prepared with SAMs were incubated with FN overnight. The cell binding sites were quantified on each surface using an antibody that targets the synergy binding site of the cell binding domains (HFN7.1) and the topography of the FN on the surfaces was evaluated with atomic force microscopy. The topography data demonstrated that the availability of cell binding domains is dependent on surface-mediated FN binding orientation. Cell spreading was assessed using a lipid membrane stain, maleimide. The cells were imaged by fluorescence microscopy and the cell area calculated. The percentage of cell adhesion was determined using a centrifugal force assay. Both keratinocyte assays suggested that the charge of the surface was the prominent factor in determining cell function on the surface over the surface wettability. The findings of this study strongly suggest that a positively charged implant surface with a FN coating will enhance the strength of the cutaneous seal around percutaneous implants over an unmodified surface.

No description available.

No description available.

Percutaneous Coronary Intervention is a common treatment for obstructive coronary artery disease, in both planned and emergency settings. Its use in the United Kingdom and elsewhere has increased dramatically in recent years due to its efficacy in the management of Acute Coronary Syndromes, increased access to PCI services, and more permissive patient selection practices. Further, a patient undergoing PCI now is likely to be treated quite differently than the same patient ten years ago, with the emergence of new interventional techniques, devices, stent types, and drugs. The widespread adoption of transradial access in favour of transfemoral access in particular has marked a new era in the delivery of PCI in the UK. Due to the rapid changes in patient and treatment characteristics, evidence generated in settings that no longer reflect the radial era is increasingly irrelevant. This thesis addresses this evidence deficit using data from the British Cardiovascular Intervention Society national PCI registry to describe contemporary trends in PCI practice and investigate the potential implications of these trends on the quality of PCI delivery. It focuses on the relationship between procedural volume, arterial access site, and short-term mortality which has not been explored in radial-era UK practice. Broadly, three research questions were posed: (1) What are the qualities and limitations of the British Cardiovascular Intervention Society PCI Registry in answering questions about routine clinical practice in the United Kingdom? (2) What is the impact on PCI outcomes of changes to the underlying patient population, changes to the selection of these patients, and changes to the treatment of these selected patients? (3) What are the consequences of these changes on the relationship of procedural volume and access site on outcomes? This thesis has showed that those centres adopting radial access more readily did not experience a decline in femoral quality, and in the most recent period were associated with better outcomes overall, particularly amongst the highest volume centres. Operator volume itself however was not associated with improved outcomes, suggesting the organisation of PCI services is not leaving operators with too few, or too many, procedures to perform competently. The current trajectory in UK practice of increasing radial adoption should continue unabated, with radial access considered as the primary access route across all clinical settings wherever possible.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2001. / Härtill 6 uppsatser.

The transdermal delivery of drugs has a lot of advantages above other routes of delivery, such as the avoidance of first-pass hepatic and intestinal metabolism, the non-invasive infusion of drugs, etc. However, the transdermal delivery of drugs, especially hydrophilic drugs, is limited due to the lipophilic nature of the stratum corneum. Methotrexate is a folic acid antagonist with antineoplastic activity and is used for the treatment of psoriasis and Kaposi's sarcoma. The permeation of methotrexate through the skin for systemic use is however limited due to its high molecular weight, the fact that it is mainty dissociated at physiological pH and its hydrophilic nature (Alvarez-Figueroa et al.. 2001). Thus the aim of my study was to enhance the permeation of methotrexate with the use of terpene. Terpenes are lipophilic in nature and have Log P values of around 2-4 (Godwin & Michniak, 1999). These characteristics make them excellent candidates as penetration enhancers. Terpenes are not only used for penetration enhancers, but in a huge number of other products, such as aromatherapeutic oils. For this reason the permeation of the terpenes through human skin and the effect of methotrexate on this permeation were also determined. The following enhancers were used in this study: menthol, menthone. isomenthol, limonene, B-myrcene, a-pinene and 1,8-cineole Five different sets of experiments were done in this study: a) a control experiment with methotrexate in the absence of the terpenes without ethanol; b) a control experiment with methotrexate in the absence of the terpenes with ethanol: c) experiments with methotrexate in the presence of the terpenes; d) control experiments with the terpenes in the absence of methotrexate and e) experiments with tile terpenes in the presence of methotrexate. For this study only human female abdominal skin was used. A saturated solution of methotrexate in water:propylene glycol (50:50) with a pH between 4 and 5 (Vaidyanathan et al., 1985) was used as the model drug and the receptor phase was PBS-buffer (pH=74) and water:ethanol (50:50) for HPLC and GC analysis respectively. The dilfusion apparatus used consisted of Vertical Franz diffusion cells with a capacity of 2 ml and a diffusion area of 1.075 cm2. The cells were placed in a water bath (+- 37 "C) on magnetic stirrers for the duration of the experiment. After the receptor phase was placed in the receptor compartment the cells were equilibrated for an hour before putting 25 ul of a 5% terpene solution in absolute ethanol on the skin in the donor compartment. This was left for half and hour to allow evaporation of the ethanol. The saturated solution of the methotrexate was now placed on the skin in the donor compartment. The experiments for methotrexate stretched over a period of 12 hours and samples were collected every 2 hours. The terpene experiments were performed over a 24-hour period and samples were taken at 2,4,6,12 and 24 hours. The concentration methotrexate permeated was determined by using HPLC-analysis and terpenes by using GC-analysis. The flux (ug/cm2/h), kp(cm/h), lag time (h) and enhancement ratio were calculated to compare the methotrexate permeation in the control and actual experiments. The results showed that a-pinene, B-myrcene and isomenthol enhanced the permeation of methotrexate most, although all the terpenes had an enhancing effect. They produced a 4- fold increase in the flux values of methotrexate. Due to the fact that the terpene experiments were only a semi-quantitative evaluation only the percentage terpenes that permeated was calculated. The experiments were done on all the terpenes except apinene. All the terpenes permeated the skin with menthol having the highest permeation. The results also showed that methotrexate did have an effect on the terpene permeation. Menthone and menthol's permeation was higher in the presence of methotrexate, while the other terpenes had a higher permeation in the absence of methotrexate. The reason for this is not clear. In conclusion, the study revealed that the enhancers used did have an enhancing effect on methotrexate permeation. This could be due to the extraction or disruption of lipids by the terpenes (Zhoa & Singh, 2000) or an increase in diffusivity and partitioning. The terpene experiments also showed that the terpenes do permeate the skin and that methotrexate does have an effect on this permeation. / Thesis (M.Sc.)--North-West University, Potchefstroom Campus, 2004.