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- Guorgis, Ghassan, 1978-
(författare)
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Understanding Skin Cancer Risk and Prevention : with Emphasis on Actinic Keratosis Patients
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The rising incidence of skin cancer globally makes it important to emphasize preventive measures that promote sun protection, particularly among individuals with phenotypic predisposition and/or risky sun habits. Actinic keratosis (AK) is the predominant actinic lesion observed in fair-skinned populations, recognized as a sign of actinic skin damage and as an occasional precursor to squamous cell carcinoma (SCC). The aim of this thesis was to explore, from a primary care perspective, how an enhanced understanding of risk factors for skin cancer development can aid in identifying individuals for patient education on prevention and early detection of skin cancer. Paper I suggests that personalized sun protection advice delivered in person by the GP can result in both short-term and long-lasting improvements in sun protective behaviour. Paper II demonstrated that individuals diagnosed with AK face a significantly elevated risk of developing SCC, basal cell carcinoma (BCC), or malignant melanoma (MM) in the following decade compared to sex- and age-matched controls. Paper III highlighted the fact that the presence of chronic lymphocytic leukaemia, and to a lesser degree hypertension and Parkinson's disease, independently raises the risk of skin cancer. This underscores the importance of providing tailored preventive guidance to individuals with these conditions. Paper IV showed that both age and male gender were factors found to be associated with an increased risk of developing skin cancer in AK patients while no risk increase was identified for any of the other variables studied. In conclusion, personalized sun protection advice from general physicians (GPs) can bring about lasting improvements in sun protective behaviour. Reinforcing this advice during medical consultations, such as nevi checks, is important to sustain this effect over a long period. This is encouraging for the accepted practice of giving sun protection advice to patients with MM, SCC and BCC. A diagnosis of AK not only indicates an increased risk of skin cancer but also serves as a readily identifiable criterion for implementing personalized preventive measures. The presence of AK substantially increases the likelihood of developing future skin cancer, even more pronouncedly when combined with specific comorbidities such as chronic lymphocytic leukaemia, hypertension, and Parkinson's disease. Future research should investigate how sun protection advice interacts with other behavioural counselling and evaluate its effectiveness over time. Additionally, exploring other factors influencing skin cancer risk in individuals with AK would facilitate the provision of comprehensive preventive interventions.
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| 2. |
- Clifford, Jenny, 1980-
(författare)
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Gold allergy : In vitro studies using peripheralblood mononuclear cells
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Positive patch test reactions to gold are commonly seen in dermatology clinics, but it is veryunusual for the patients to actually have any clinical symptoms. It is also common with irritantreactions that are not linked to adaptive immunity. Therefore, a deeper understanding of themechanisms underlying allergic contact dermatitis (ACD) reaction, and the search for acomplementing diagnostic tool, is important.In paper I we included three subject groups; one with morphologically positive patch testreactions to gold sodium thiosulphate (GSTS, the gold salt used in patch testing), one withnegative patch tests, and one with irritant reactions to gold. Blood samples were collected andexamined regarding the proliferation rate and which cytokines were secreted after culturingwith GSTS. We saw that the cultured lymphocytes from the allergic donors proliferated at asignificantly higher rate than the two other subject groups, and that the cells secreted cytokinesof both Th1 (Interferon (IFN) -g and Interleukin (IL) -2) and Th2 (IL-13 and IL-10) types. Theallergic donors secreted significantly higher levels of IFN-g, IL-2 and IL-13 than the two othersubject groups. Both the negative and irritant subject groups showed suppressed levels of thecytokines as compared with the unstimulated cultures, demonstrating the immunosuppressingeffects of gold.We also examined whether any of the analyzed markers, alone or combined, could be usedas an aid for diagnosing ACD to gold. We found that the IFN-g assay yielded the highestsensitivity (81.8 %) and specificity (82.1 %), and also identified 87.5 % of the irritant group asnon-allergic.In paper II we decided to investigate what cell types and subsets that reacted to the goldstimulation. We analyzed proliferation rate and expression of CD45RA, CD45R0, cutaneouslymphocyte-associated antigen (CLA) and the chemokine receptors CXCR3, CCR4 andCCR10. Similar to what has previously been published about nickel (Ni) allergy, the cells fromthe gold-allergic subjects that reacted to the GSTS stimulation expressedCD3+CD4+CD45R0+CLA+. However, contrary to findings in studies on Ni-reactive cells, wesaw no differences between allergic and non-allergic subjects regarding any of the chemokine receptors studied.In conclusion, we found that analysis of IFN-g might be a useful complement to patchtesting, possibly of interest in avoiding the need for repeated tests to rule out irritant reactions.We also saw that the cells that proliferated in response to gold were memory T-cells expressingCD4 and CLA, the marker for skin-homing. However, these cells did not express elevatedlevels of any of the chemokine receptors analyzed, showing that there are both similarities anddifferences between the mechanisms for Ni allergy and gold allergy.
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| 3. |
- Falk, Magnus, 1968-
(författare)
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Towards a broader use of phototesting : in research, clinical practice and skin cancer prevention
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In western societies, skin cancer incidence has increased dramatically over recent decades, due predominantly to increased sun exposure habits. Ultraviolet (UV) light exposure and individual light sensitivity of the skin constitute two important factors affecting the risk for skin cancer development. Individuals with a heightened propensity to get sunburnt have a higher risk for skin malignancies, and need to protect themselves more systematically from the sun. Individual UVlight sensitivity can be determined either by self-estimation of tendency to burn and tan, as in the Fitzpatrick’s classification, or by use of a phototest. Although phototesting constitutes a considerably more objective method, it is only sparsely used, chiefly due to financial and resource related factors, and is mainly limited to investigation of photodermatoses or dose-management in photo therapy.The general aim of this thesis was to develop and improve aspects of the phototest procedure in rder to broaden the utilisation of phototesting within the fields of research, clinical practice and skin cancer prevention. As a first step, a new phototesting technique, using a divergent UVB beam was evaluated. The principle of the method is to provoke a circular UVB-erythema in the skin, the diameter of which is related to the administered dose and thus the Minimal Erythema Dose (MED). In a test group of healthy subjects, naked eye reading by a trained observer resulted in a more exact, estimation of UVB-sensitivity, compared to traditional phototesting. Since the diffuse border of the provoked erythema was challenging for the untrained observer to read, the need for an objective, bio-engineering technique for test reading was clear. In this thesis, Laser Doppler perfusion imaging (LDPI) has been used. This data also enabled an objective description of doseresponse for the reaction, an outcome not possible in traditional testing. The divergent beam method was also shown to be useful as a model for evaluation of the effect of topically applied substances.In order to broaden the utilisation of phototests in general, a test procedure built on patient performed self-reading of skin tests (a traditional phototest and an irritant patch test) was evaluated. The reliability of these self-readings was shown to be substantial when compared to the control readings of a trained observer.Using the self-reporting procedure, phototesting was evaluated as a tool in primary prevention of skin cancer. The study focussed on sun habits and sun protection behaviour, and also on investigating the impact of different forms of presentation of the preventive information. Results showed significantly higher impact for a personally mediated preventive message than by letterform. For individuals with heightened UV-sensitivity the performance of a phototest led to a greater tendency to adopt sun protection behaviour than for subjects with a lower UV-sensitivity, suggesting that phototesting is a useful way to improve the outcome in terms of preventive behaviours for this group of susceptible, at-risk individuals.Divergent beam phototesting, patient-performed self-reading, and the application of phototesting in skin cancer prevention emerge as three novel, previously little investigated, aspects of phototesting, for which promising results could be demonstrated.
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| 4. |
- Toll, Rani, 1975-
(författare)
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To See or Not to See : A Study on Capillary Refill
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Assessment of the critically ill is traditionally based on vital signs (blood pressure, pulse, respiratory rate, temperature and level of consciousness). Altered vital signs are, however, late indicators of deranged hemodynamics pointing to a need for additional, more sensitive markers of circulatory compromise. In the beginning of the 20th century, the capillary refill (CR) time evolved as a possible, non-invasive adjunct to early prediction of the outcome in the critically ill. The manoeuvre entails application of blanching pressure on the skin of the finger pulp or sternum for 5 seconds. After release of the pressure, the observer estimates time in seconds for the skin to return to original colour. This time is hypothesized to reflect the dynamics of the microcirculation and its possible connection with hemodynamics. In the 1980s the “normal capillary refill time” was set to < 2 seconds and later extended to 3 seconds, without a clear scientific foundation. Naked-eye estimations of CR time met increasing scepticism in the 1990s due to subjectivity and poor prognostic value for shock or death. Several basic traits, such as age and sex, as well as ambient temperature, were also shown to independently influence the CR time. Various methods have evolved with the capability to measure CR time quantitatively, one of which is Polarisation Spectroscopy Imaging (PSI). PSI measures the Red Blood Cell (RBC) concentration in tissue (e.g. the skin) and can be used to measure CR time.Objectives: The purpose of this study was to establish basic characteristics for quantified CR (qCR), identify possible influencing factors in healthy subjects and to investigate how this relates to current practice. We also sought to identify technical demands for transfer of the technique into clinical studies. In paper I we analysed the (qCR) time characteristics at 5 different skin sites (forehead, sternum, volar forearm, finger pulp and dorsum finger). The objective of paper II was to investigate the inter- and intra-observer variability of naked eye CR assessments of different professions, nurses, doctors and secretaries (representing laymen). In paper III we observed the effect of low ambient temperature on the qCR time in different skin sites. In paper IV, we transferred the equipment from a laboratory to a clinical setting in the Emergency Department (ED) for application on potentially critically ill patients. In this study we evaluated the most important factors determining a reliable data collection and influencing the amount of data possible to analyse.Methods: qCR time was measured in a total of 38 volunteers and 10 patients in different skin sites (2-5 skin sites) at different ambient temperatures. PSI (TiVi 600 and 700, WheelsBridge AB, Linköping, Sweden) was used to determine the rapid temporal changes in RBC concentration in skin during the CR manoeuvre. Films using a range of the first measurements from paper I were shown for assessment to 48 observers working in the ED.Results: In paper I we could delineate qCR curves and suggest 2 possible equivalents to the naked-eye observed CR time which we named Time to Return to Baseline 1 (tRtB1) and Time to Peak (tpk). We demonstrated differences in qCR-curves depending on skin site and possibly due to skin temperature. In paper II we showed a poor inter- and intra-observer reproducibility in visually estimating the CR time regardless of profession (clinicians or laymen). Paper III demonstrated a rapid effect of ambient temperature on qCR time in peripheral skin sites such as finger pulp. The forehead, regarded as a more central skin site was the most temperature stable site and showed least variability in qCR time as determined using tRtB1. Paper IV, a study on patients in an ED setting, yielded assayable data in 80% of the measurements. We identified critical performance parameters to address in the further development of a more robust, easy-to-use device for future validation of the possible relevance of qCR in patient triage and monitoring.Conclusions: CR time can be quantified using PSI. Quantified CR time demonstrated a large variability between different skin sites, specifically, skin temperature was shown to be an important factor influencing qCR time, particularly at the fingertip. Naked-eye estimates of CR time were highly variable, both within and between observers. Agreement between quantified CR time and naked-eye estimates was poor. The prototypic PSI technique was feasible in a clinical setting and, with further improvements, clinical evaluation of qCR in relation to relevant patient outcomes will be possible.
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