I DEVELOPED A NEW HIGH THROUGHPUT DUAL CHANNEL HYPERSPECTRAL IMAGING CONFIGURATION BASED ON ACOUSTO-OPTIC TUNABLE FILTER. THE DEVELOPED IMAGING SYSTEM WAS CHARACTERIZED AND EVALUATED IN COMPARISON WITH OTHER CONVENTIONAL CONFIGURATIONS. THE NEW IMAGING SYSTEM PROVED HIGHER THROUGHPUT WITH RESPECT TO THE CURRENTLY USED CONFIGURATIONS.THE IMAGING SYSTEM WAS THEN USED TO QUANTITATIVELY ASSESS AND PRECISELY CLASSIFY SKIN ERYTHEMA INDUCED ARTIFICIALLY ON VOLUNTEERS AND NATURALLY ON SKIN CANCER PATIENTS DUE TO RADIOTHERAPY TREATMENT. / Recent cancer statistics show that 40% of Canadians might contract cancer during their life and 25% of Canadians might die due to cancer. In skin, head and neck cancers, surgery and radiation therapies are the most prevalent treatment options, while radiation therapy is the most commonly used approach. A common problem in radiation therapy is tumors behave differently against ionizing radiation. For instance, with the same dose, some tumors are fully damaged or shrunk, while others are less affected. The difference in individual tumor response to therapy is transformed into a research question: how to quantitatively assess tumor response to radiation and how to tune radiation therapy to achieve full destruction for tumor cells? Few past studies addressed the question, although no definite answer was realized. This work is a part of a project that investigates the hypothesis that radiation response of skin is correlated to individual tumor response. In the case of high correlation, the skin’s faster response to ionizing radiation can be used to modify the irradiation dose to achieve the maximum destruction of individual’s tumor. To examine the project hypothesis, radiation-induced skin redness or erythema was selected as an acute skin reaction to being objectively quantified. Hence, the overall goal of the research thesis work is to objectively assess and precisely quantify radiation-induced erythema or radiation dermatitis. Skin erythema was assessed formerly by multiple optical and non-optical modalities. The current gold standard is the visual assessment (VA). Unfortunately, VA lacks objectiveness, precise communication, and quantification. To push the limitations of VA and past techniques, hyperspectral imaging (HSI) was proposed to be used for erythema assessment. The work detailed in this thesis aims to create more confidence in HSI to be utilized toward objectively quantify skin erythema. To reach this goal, initially, a new high-throughput dual channel acousto-optic tunable filter (AOTF)-based-HSI instrument was developed for monitoring radiation dermatitis. AOTF-HSI instrument design, implementation, and full characterization are presented. Second, the developed AOTF-HSI instrument is evaluated against a liquid crystal tunable filter (LCTF) instrument. Third, to be prepared for clinical operation, the AOTF-HSI equipment was used to classify an artificially-induced erythema on healthy volunteers in an exploratory study. A robust linear discriminant analysis (LDA)-based classification method was developed for the purpose of image classification. Finally, HSI instrument and LDA classification method were utilized in a preliminary clinical study to properly monitor and precisely quantify radiation dermatitis for skin cancer patients. In the clinical study, erythema indices were computed using Dawson’s method. Least square fitting was used to fit the acquired absorbance data, and thus quantify the hemoglobin concentration change along the study duration. Moreover, LDA was used to contrast spectral and digital imaging for erythema classification. In sum, the work documented in this thesis was willfully directed to achieve an efficient, portable, user-friendly hyperspectral imaging system which has the opportunity to be a benchtop in the clinical daily procedure in the near future. / Thesis / Doctor of Philosophy (PhD)

Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 5 uppsatser.

Erythromelalgia is a rare clinical syndrome characterized by heat, redness and intermittent pain in the extremities, being most frequent the bilateral development in the lower extremities. Local cooling brings relief to symptoms, while heating, physical exercises and use of stockings/socks intensify the discomfort. This condition can be primary or idiopathic or secondary to haematological disorders and vascular inflammatory and degenerative diseases. It is reported the case of an eighteen-year-old male who presented, at the early age of two, development of the symptoms of erythema, heat and pain followed by desquamation of hands and feet, in outbreaks, with intervals 4 to 5 years long between the crises.

MSc (Med), Dept of Pathology, Division of Human Genetics, Faculty of Health Sciences, University of the Witwatersrand / Keratolytic winter erythema (KWE) or Oudtshoorn skin disease is a rare monogenic autosomal dominant condition with an unknown cause. KWE is a disorder of epidermal keratinisation that involves the necrobiosis of the Malpigihian layer of the palmoplantar skin with the consequent dissection of the stratum corneum. This cutaneous disorder was first described by Findlay et al. (1977) and occurs with a high prevalence of 1/7200 in the South African Afrikaans-speaking white population and with a lower, but unspecified prevalence in the Coloured population. The primary objective of this study was to identify and characterise the causative gene for KWE, by examining plausible positional candidate genes. The KWE gene has been localized to chromosome 8p23.1-p22 in a region of 1.2 Mb. In order to identify a potentially causative KWE mutation, the coding regions of each candidate gene was sequenced from genomic DNA. Each of the genetic variants identified was also observed in the control group or had previously been shown to be polymorphic, eliminating them all from causing KWE. The cDNA of the two most likely candidates, FDFT1 and CTSB, was sequenced in order to identify deep intronic variants that might affect splicing and that would not be identified at a genomic DNA level. No such variation was observed. The relative expression profiles of CTSB and FDFT1 in affected and non-affected palmoplantar skin was analysed using real-time RT-PCR. The relative expression of CTSB in the skin of patients did not differ significantly from controls (p=0.68). However, a trend was observed towards increased expression of FDFT1 in the skin of KWE affected individuals (p=0.063). This observation prompted the analysis of the FDFT1 promoter region through genomic sequencing. No genetic variants identified within the promoter region segregated with the KWE phenotype. The increased FDFT1 expression is therefore unlikely to result from a mutation within the promoter region of this gene and may be in response to the disruption of the epidermal barrier in affected skin. There is a strong correlation between the severity of the KWE phenotype and the level of FDFT1 expression. Although none of the chosen positional candidate genes appear to harbour the KWE-causing mutation, they can be excluded from the list of possible positional candidates for KWE, taking us one step closer to discovering the molecular cause of KWE.

Thesis (M.S.)--University of Missouri-Columbia, 2008. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on August 12, 2009) Vita. Includes bibliographical references.

The clinical manifestations, including variations, of the Stevens-Johnson syndrome (SJS) are reviewed. Lesions of the skin, eye, and mucous membranes are described and discussed. The potential complications and therapeutic approaches are outlined. Finally, the review discusses the controversy over the use of systemic corticosteroids in this syndrome.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 5 uppsatser.

Radiation therapy has been shown to increase local and regional control as well as overall survival with breast cancer, but the vast majority of patients develop acute skin reactions, which are in part related to microvascular changes. These reactions vary between different skin sites. The aim of this work is to determine the absorbed dose to the skin by measurements and investigate if there is a correlation between the absorbed dose at different areas of the breast and the local changes in microcirculation in the skin after breast cancer radiotherapy. The study includes characterisation of the Gafchromic EBT3 film and Epson Perfection V600 Photo scanner which are used for absorbed dose determination. The measurements were done both on an anthropomorphic female phantom and on a patient undergoing breast cancer radiotherapy. Twenty-one pieces offilm (2x1 cm2) were placed on the surface of the breast (both for the phantom and patient) and irradiated with a prescribed dose to the target of 2.66 Gy with two opposed fields using 6 MV beam. It was observed that mainly 45-64 % of the prescribed dose was deposited at the surface, both for the phantom and patient. Using laser speckle contrast imaging and polarised light spectroscopy, the regional changes in mean blood perfusion and in mean red blood cell concentration (RBCC) at the end of the treatment with a total prescribed dose of 42.6 Gy, compared to baseline, were measured in both the treated and untreated breast of the same patient. Although marked increases in perfusion were seen in different areas of the treated breast, there was no significant correlation between the changes in perfusion and the absorbed dose at these areas. However, a statistical correlation was found between the changes in RBCC and the absorbed skin dose at the same areas. To further elucidate the relation between the changes in skin microcirculation and the absorbed radiation dose during breast cancer radiotherapy, future studies using a larger number of patients are needed.

Background: Previous literature showed contradictory evidence on the subject of predictors of chemotherapy-induced Palmar Plantar Erythrodysesthesia (PPE). While there is evidence to suggest that dose and schedule of the drugs play a large role, the fact that many still go on to develop severe PPE following dose reduction would indicate that there are other factors involved. Since the incidence of PPE is more prevalent during the first three cycles of treatment this would also indicate that there are factors other than a cumulative effect. The contradictory evidence in the literature relates to biographical factors, performance status, co-morbidities and renal function. There is a lack of empirical evidence to support the theory that PPE is caused by damage to the microcapillaries due to everyday activities that cause friction or pressure to the hands or feet. Purpose: The aim of this exploratory study was to identify pre-treatment risk factors for the development of PPE prior to cycle four. Patients and methods: The study was made up of two phases, a retrospective phase and a prospective phase, using mixed strategies to collect data. Thus providing two independent samples to compare and validate or refute results. Phase I: A retrospective notes review of patients who had received Infusional 5FU or capecitabine containing regimes over a 1 year period (n=392). Phase II Prospective data collection from participants receiving capecitabine monotherapy (n = 125). Data was collected during semi-structured interviews, from participant's diaries, physical examination of the hands and feet and notes review. Data relating to activities that cause friction, pressure or heat were collected during this phase. Data from both samples were analysed independently using bivariate (chi-square and t-test) tests where each independent variable was analysed against PPE. The variables which achieved statistical significance were entered into a multivariate (binary logistic regression) model. The multivariate analysis employed a specific modelling algorithm using a relaxed alpha value applied to various entry methods to produce multiple models. The outcomes from these models were entered into a ROC curve test to establish which model was the best predictor of PPE. Results: Phase I The bivariate analysis demonstrated that those at most risk of developing PPE prior to cycle 4 of capecitabine monotherapy were males with non-metastatic colorectal cancer, who had either developed PPE with previous chemotherapy regimes or not had previous chemotherapy and who started their treatment during the winter months. When variables were combined in a multivariate logistic regression model, those that were associated with an increased risk of PPE were male, no metastatic spread, no inflammatory condition as co morbidity, smoked, did not drink, had weight loss prior to treatment, a low/normal pre treatment ALP level and started their treatment during the winter. Phase II: The bivariate analysis demonstrated that those at most risk of developing PPE prior to cycle 4 of capecitabine monotherapy were those with no metastatic disease, had an inflammatory condition as co morbidity, were receiving capecitabine as adjuvant treatment, had a good performance status (0-1) and had a tendency to have warm hands. When variables were combined in a multivariate logistic regression model, those that were associated with an increased risk of PPE were younger (< 65) had no metastatic disease, an inflammatory condition as co morbidity, drank alcohol regularly, had a good performance status, had not received previous radiotherapy, were overweight or obese, had a pre treatment creatinine clearance of 30-50mls/min and had a tendency to have warm hands. Conclusions: Similarly to the literature, contradictory findings were seen between the two samples within this study. There was only one variable that was associated with the development of PPE prior to cycle 4, which was the absence of metastatic disease. Limitations of retrospective data may explain variation in some variables which may have been underreported; however it is likely that it is not possible to identify specific factors that increase the risk of PPE. This is the first study to have collected and analysed data related to friction, pressure and heat causing activities. These activities have been suggested as increasing the risk of developing PPE and form the basis of patient education to avoid these activities. Data from this study indicates that only a tendency to have warm hands is associated with an increased risk of PPE. Whilst this finding would need validating in larger studies, it is a unique contribution to the body of knowledge of PPE. This finding indicates that avoidance of activities that cause friction and pressure has no evidence base. Patients may therefore be avoiding activities that add to their enjoyment which at this stressful time in their lives may add to any psychological distress. Despite limitations of this study, the importance of the findings presented here lie in its usefulness in shaping future research to investigate identified variables, where before no direction was available.

The spotted fever group rickettsiae are emerging diseases. They cause damage in their hosts by invading the endothelium in small to medium-sized blood vessels, which results in vasculitis that can cause clinical manifestations from most organs. The present thesis describes the prevalence of Rickettsia helvetica in ticks, the incidence of rickettsial infection based on seroreactivity and seroconversion in humans and their symptoms, from different parts of Sweden and the Åland Islands in Finland. This was accomplished through serological analysis of both retrospective and prospective serum samples from confirmed and suspected tick-bitten individuals compared to individuals with no knowledge of tick exposure (blood donors). We found a comparable seroprevalence to Rickettsia spp. in different geographical areas where ticks are present; it was also comparable to the seroprevalence of Borrelia spp. Seroprevalence was also more common, as suspected, in the tick-exposed group compared to blood donors. In comparison with co-infections with other tick-borne infections (Anaplasma spp. and Borrelia spp.), we could conclude that co-infections do exist and that, based on clinical findings, it is difficult to distinguish which microorganism causes certain clinical manifestations. For reliable conclusions regarding the causative microorganism, the diagnosis should basically rely on diagnostic tests. In comparison with Borrelia spp., seroconversion to Rickettisa spp. was more common in the areas we investigated, indicating that rickettsiosis is a common tick-borne infection in Sweden and most likely underdiagnosed. When investigating patients with meningitis, we found R. felis in cerebrospinal fluid from two patients with subacute meningitis. This was the first report in which R. felis was found and diagnosed in patients in Sweden. The patients recovered without sequelae and without causal treatment. To provide guidelines on when to treat Rickettisa spp. infections, more investigations are needed. The present thesis shows that Rickettsia spp. are common in ticks and do infect humans. Rickettsial infection should be considered in both non-specific or specific symptoms after a tick bite. It was also shown in the thesis that flea-borne rickettsiosis (R. felis) occurs in Sweden and may cause invasive infections