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Every year approximately 2800 Swedes are diagnosed with malignant melanoma, the form of cancer that is most rapidly increasing in incidence in the Western world. The earlier we can identify and diagnose a malignant melanoma, the better is the prognosis. In Sweden, 155 000 benign naevi, harmless skin tumours or moles, are surgically excised each year, many of them because melanoma cannot be dismissed by non-invasive methods. The excisions result in substantial medical costs and cause unrest and suffering of the individual patient. For untrained physicians, it is often difficult to make an accurate diagnosis of melanoma, thus a tool that could help to strengthen the diagnosis of suspected melanomas would be highly valuable. This thesis describes the development and assessment of a non-invasive method for early skin cancer detection. Using near infrared (NIR) and skin impedance spectroscopy, healthy and diseased skin of various subjects was examined to develop a new instrument for detecting malignant melanoma. Due to the complex nature of skin and the numerous variables involved, the spectroscopic data were analysed multivariately using Principal Component Analysis (PCA) and partial leas square discriminant analysis (PLS-DA). The reproducibility of the measurements was determined by calculating Scatter Values (SVs), and the significance of separations between overlapping groups in score plots was determined by calculating intra-model distances.

The studies indicate that combining skin impedance and NIR spectroscopy measurements adds value, therefore a new probe-head for simultaneous NIR and skin impedance measurements was introduced. Using both spectroscopic techniques it was possible to separate healthy skin at one body location from healthy skin at another location due to the differences in skin characteristics at various body locations. In addition, statistically significant differences between overlapping groups of both age and gender in score plots were detected. However, the differences in skin characteristics at different body locations had stronger effects on the measurements than both age and gender. Intake of coffee and alcohol prior to measurement did not significantly influence the outcome data. Measurements on dysplastic naevi were significantly separated in a score plot and the influence of diseased skin was stronger than that of body location. This was confirmed in a study where measurements were performed on 12 malignant melanomas, 19 dysplastic naevi and 19 benign naevi. The malignant melanomas were significantly separated from both dysplastic naevi and benign naevi.

Overall, the presented findings show that the instrument we have developed provides fast, reproducible measurements, capable of distinguishing malignant melanoma from dysplastic naevi and benign naevi non-invasively with 83% sensitivity and 95% specificity. Thus, the results are highly promising and the instrument appears to have high potential diagnostic utility.

Background/purpose: Near-infrared (NIR) spectroscopy and skin impedance (IMP) measurements are useful techniques for objective diagnostics of various skin diseases. Here, we present a combined probe head for simultaneous, time-saving NIR spectroscopy and skin impedance measurements. The probe also ensures that both measurements are performed under equal conditions and at the same skin location.

Methods: Finite element method simulations were performed for evaluation of the impedance. In vivo skin measurements were performed and combined NIR and impedance spectra were analysed by means of multivariate methods with respect to body location, age and gender. The classification rate was determined by a planar discriminant analysis. Reproducibility was investigated by calculation of scatter values and statistical significance between overlapping groups was assessed by the calculation of intra-model distances, q.

Results: The novel probe yielded rapid reproducible results and was easy to manage. Significant differences between skin locations and to a lesser extent age groups and gender were demonstrated.

Conclusion: With the novel probe, statistically significant differences between overlapping classes in score plots can be confirmed by calculating intra-model distances. The influence of molecular differences in the skin at different body locations is larger than the influence of gender or age and therefore relevant reference measurements are discussed.

Near infrared spectroscopy (NIR) and skin impedance (IMP) spectroscopy are two methods suggested for diagnoses of diseases inducing adverse effects in skin. The reproducibility of these methods and their potential value in non-invasive diagnostics were investigated. Measurements were performed in vivo on healthy skin at five anatomic body sites on eight young women. partial least squares discriminant analysis showed that both methods were useful for classification of the skin characteristics at the sites. Inter-individually the NIR model gave 100% correct classification while the IMP model provided 92%. Intra-individually the NIR model gave 88% correct classification whereas the IMP model did not provide any useful classification. The correct classification was increased to 93% when both datasets were combined, which demonstrates the value of adding information. Partial least squares discriminant analysis gave 72% correct predictions of skin sites while the combined model slightly improved to 73%.

Background/purpose: Near infrared (NIR) and impedance spectroscopy can be used for clinical skin measurements and need to be evaluated for possible confounding factors; (a) are skin conditions of the patient and the subsequent skin measurements influenced by alcohol and/or coffee consumption and (b) are measurements of dysplastic naevi (DN) reproducible over time and significantly different compared to reference skin.

Methods: NIR and skin impedance spectroscopic data were analysed multivariately. In the first study, the skin characteristics of 15 healthy individuals were examined related to body location, gender, individual differences, and consumption of coffee or alcohol. The second study included five patients diagnosed with dysplastic naevi syndrome (DNS). Measurements were taken on DN and reference skin over time.

Results: In the first study, body location and gender had a major influence on measurement scores. Inter-individual skin characteristics and coffee or alcohol effects on skin characteristics were of minor importance. In the second study, it was shown that DN can be differentiated from reference skin and the measurements are stable over time.

Conclusions: Moderate consumption of alcohol and coffee did not influence the results of the measurements. It is possible to follow, stable or changed, characteristics of DN over time.

Background/purpose: An early diagnosis of cutaneous malignant melanoma is of high importance for good prognosis. An objective, non-invasive instrument could improve the diagnostic accuracy of melanoma and decrease unnecessary biopsies. The aim of this study was to investigate the use of Near infrared and skin impedance spectroscopy in combination as a tool to distinguish between malignant and benign skin tumours.

Methods: Near infrared and skin impedance spectra were collected in vivo on 50 naevi or suspect melanomas prior to excision. Received data was analysed with multivariate techniques and the results were compared to histopathology analyses of the tumours. A total of 12 cutaneous malignant melanomas, 19 dysplastic naevi and 19 benign naevi were included in the study.

Results: The observed sensitivity and specificity of the proposed method were 83% and 95%, respectively, for malignant melanoma.

Conclusions: The results indicate that the combination of near infrared and skin impedance spectroscopy is a promising tool for non-invasive diagnosis of suspect cutaneous malignant melanomas. 

This case study includes 73 fatally and nonfatally injured passengers from a level-crossing train crash in Nosaby, Sweden, in 2004. The aim was to identify the injury panorama and the injury objects and to determine the injury-inducing variables. Data were analyzed with descriptive statistics, quantitative content analysis, and multivariate data analysis. The first carriage overturned, and its occupants were the ones who suffered the most severe and lethal injuries. Injury type and injury location for these passengers also differed significantly from the passengers on the other two carriages. Tables significantly influenced injury type and injury location in all carriages, whereas the injured persons’ seating position had significant effect only in the second and third carriage. Those who had travelled facing forward with a table in front of them in Carriages 2 and 3 were more likely to have sustained injuries to their abdomen or pelvis. Other injury-inducing objects were seats, interior structures, wood pellets from the truck, and other passengers. Neck sprains were significantly more prevalent among those who had travelled facing backward. Improved train crashworthiness also needs to include interior safety, which would have a potential to reduce crash injuries.

Many studies have suggested the hypothesis that the plasminogen activator (PA) system and the matrix metalloproteinase (MMP) system, either separately or in combination, may provide the proteolytic activity that is required for rupture of the follicular wall at the time of ovulation. Our recent studies on ovulation in plasminogen (plg)-deficient mice have, however, shown that plasmin is not required for normal ovulation, leading us to the hypothesis that MMPs may be a more important source of proteolysis for this process. To investigate the role of MMPs and also the possibility of a functional overlap or synergy between the MMP and PA systems during ovulation, we have studied ovulation efficiency in wild-type and plg-deficient mice treated with the broad-spectrum MMP inhibitor galardin. We found that in both wild-type mice and heterozygous plg-deficient (plg(+/-)) mice that had been treated with galardin prior to ovulation, there was a mild (18-20%) reduction in ovulation efficiency. Surprisingly, galardin treatment of plg-deficient (plg(-/-)) mice only caused an additional 14% reduction in ovulation efficiency as compared to vehicle-treated plg(-/-) mice. Our data therefore suggest that although MMPs may play a role in degradation of the follicular wall, they may not be obligatory for ovulation. In contrast to previous studies on tissue remodeling during wound heating and placental development, we have demonstrated that there is no obvious functional overlap or synergy between the PA and MMP systems, which has previously been thought to be essential for the ovulatory process.