There is a general need for methods to obtain fast in vivo diagnosis of skin tumours. Raman spectroscopy measures molecular structure and may thus have potential as a tool for skin tumour diagnosis. The purpose of this study was to investigate how skin pigmentation influenced the Raman spectra and skin tumour diagnostics in vivo. We obtained Raman spectra in vivo from the normal skin of 55 healthy persons with different skin pigmentation (Fitzpatrick skin type I–VI) and in vivo from 25 basal cell carcinomas, 41 pigmented nevi and 15 malignant melanomas. Increased skin pigmentation resulted in a higher spectral background caused by fluorescence, which could be removed by background correction. After background correction, we found only a negligible effect of pigmentation on the major spectral bands, and the comparison of the intensity of these bands allowed us to differentiate between normal skin and the different skin lesions independent of skin type. The diagnosis of skin lesions is possible due to significant (p < 0.05) differences found in the water band around 3250 cm-1, the protein specific band around 1250 cm-1 (amide-III) and the amide-III ratio that describes the protein/lipid ratio by comparing bands around 1250 cm-1 with bands around 1300 cm-1. We have shown that NIR-FT Raman spectroscopy is useable for malignant melanoma and basal cell carcinoma diagnostics in vivo and that pigmentation of the skin or lesion does not influence the diagnosis, but larger data sets are required to establish accurate diagnostic power.

Summary Background  Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight‐mediated PDT is a simple and tolerable treatment procedure for PDT. Methyl aminolaevulinate (MAL)‐PDT is approved for the treatment of thin or nonhyperkeratotic AKs on the face and scalp. However, thick AK lesions are often treated as well when present in the field‐cancerized treatment area.

Dermal effects of KH 1060, a novel, highly potent 20-epi analogue of 1 alpha,25-dihyroxyvitamin D-3, were investigated in a hairless mouse model, During daily topical applications of a 0.4 mu M solution of KH 1060 for 4 weeks, epidermal hyperplasia and an increase of dermal thickness and mass were observed. KH 1060 upregulated glycosaminoglycan and collagen synthesis in the skin, and increased glycosaminoglycan deposition in the subepidermal region, Reverse transcription-polymerase chain reaction amplification of the transforming growth factor (TGF) beta 1-specific mRNA revealed that KH 1060 stimulated expression of this growth factor in the epidermis, but not in the dermis, Changes observed after application of 1 alpha,25-dihydroxyvitamin D-3 were much less pronounced but qualitatively similar to the effects of KH 1060, whereas structurally related but receptor inactive compounds, vitamin D-3 and 1 beta,25-dihydroxyvitamin D-3, did not produce any effects. Furthermore, we were unable to demonstrate the involvement of the non-genomic, receptor-independent vitamin D signalling in the skin, using a specific stimulator (Ro 24-2090) and a blocker (1 beta,25-dihydroxyvitamin D-3) Of this pathway. Our findings provide the first evidence that a strong Vitamin D-3 analogue triggers synthesis of skin connective tissue, possibly via vitamin D receptor activation and the paracrine action of epidermis-derived TGF-beta 1.

AIM:The aim of this study was to review published literature concerning the use of compression treatments in the management of venous and lymphatic diseases and establish where reliable evidence exists to justify the use of medical compression and where further research is required to address areas of uncertainty.METHODS:The authors searched medical literature databases and reviewed their own collections of papers, monographs and books for papers providing information about the effects of compression and randomized clinical trials of compression devices. Papers were classified in accordance with the recommendations of the GRADE group to categorize their scientific reliability. Further classification was made according to the particular clinical problem that was addressed in the papers. The review included papers on compression stockings, bandages and intermittent pneumatic compression devices.RESULTS:The International Compression Club met once in Vienna and corresponded by email in order to reach an agreement of how the data should be interpreted. A wide range of compression levels was reported to be effective. Low levels of compression 10-30 mmHg applied by stockings are effective in the management of telangiectases after sclerotherapy, varicose veins in pregnancy, the prevention of edema and deep vein thrombosis (DVT). High levels of compression produced by bandaging and strong compression stockings (30-40 mmHg) are effective at healing leg ulcers and preventing progression of post-thrombotic syndrome as well as in the management of lymphedema. In some areas no reliable evidence was available to permit recommendations of level of compression or duration of treatment. These included: management of varicose veins to prevent progression, following surgical treatment or sclerotherapy for varicose veins, and the level of compression required to treat acute DVT.CONCLUSION:This review shows that whilst good evidence for the use of compression is available in some clinical indications, there is much still to be discovered. Little is know about dosimetry in compression, for how long and at what level compression should be applied. The differing effects of elastic and short-stretch compression are also little understood.

NIR-FT-Raman spectra of skin from pig ear, guinea pig and mouse were recorded with excitation at 1064 nm and compared to spectra of human skin. The R((nu) over bar)-representation was used to eliminate the intense Rayleigh band. The total water content in each sample was estimated from the intensities of the OH-stretching vibrations at about 3200 cm(-1). A low-wavenumber band around 180 cm-1 (similar to 5.5 terahertz) was characteristic of a bulk-like liquid water structure. Water content and structure in skin from pig ear, guinea pig and human were similar and different from mouse skin. Differences in loss of bulk water were observed for skin samples after freezing and thawing. Skin biopsies of human skin with various skin tumors showed an increase of water with a bulk-like structure in skin with malignant skin tumors.

Firmly established as the leading international reference in this field, Non-Invasive Methods and the Skin broke new ground with its comprehensive coverage of methods used in both clinical and experimental dermatology. Completely revised and updated, containing more than twice as much information, the Second Edition continues the tradition. The authors' thorough research and clear organization make this book a baseline reference for those using noninvasive biophysical methods to study the skin. Arranged by physical modality and structured to provide educational and practical information, the second edition, like its predecessor, will prove to be of value to young researchers and senior scientists alike. The coverage of major evaluation and measurement methods share a consistent format, including scope, sources of error, application, and validity. This edition incorporates 69 revised chapters with more than 90 new chapters covering topics such as computer technique, imaging techniques, skin friction, barrier functions, and more.New chapters provide coverage of: computers, computer techniques, and image analysis imaging techniques, including clinical photography legal situations and guidelines behind instrumental use skin friction barrier functions important new techniques such as in vitro confocal microscopy, OCT, and Raman spectroscopy veterinary/animal research use of methods The truly interdisciplinary, international panel of contributors includes experts from the specialties of dermatology, bioengineering, pathology, manufacturing engineering, medical physics, pharmacology, microbiology, neurology, surgery, obstetrics and gynecology, cardiovascular research, and pharmacy from academic institutions and hospitals in countries such as Denmark, Germany, the United Kingdom, the United States, Japan, Israel, Taiwan, and Singapore. The revision is extensive and covers a broad spectrum of methods while providing the same caliber of authoritative information that made the previous edition so popular. Application oriented, practical, and instructive, this Second Edition will meet the needs of the researchers today, and in years to come.

Firmly established as the leading international reference in this field, Non-Invasive Methods and the Skin broke new ground with its comprehensive coverage of methods used in both clinical and experimental dermatology. Completely revised and updated, containing more than twice as much information, the Second Edition continues the tradition. The authors' thorough research and clear organization make this book a baseline reference for those using noninvasive biophysical methods to study the skin. Arranged by physical modality and structured to provide educational and practical information, the second edition, like its predecessor, will prove to be of value to young researchers and senior scientists alike. The coverage of major evaluation and measurement methods share a consistent format, including scope, sources of error, application, and validity. This edition incorporates 69 revised chapters with more than 90 new chapters covering topics such as computer technique, imaging techniques, skin friction, barrier functions, and more.New chapters provide coverage of: computers, computer techniques, and image analysis imaging techniques, including clinical photography legal situations and guidelines behind instrumental use skin friction barrier functions important new techniques such as in vitro confocal microscopy, OCT, and Raman spectroscopy veterinary/animal research use of methods The truly interdisciplinary, international panel of contributors includes experts from the specialties of dermatology, bioengineering, pathology, manufacturing engineering, medical physics, pharmacology, microbiology, neurology, surgery, obstetrics and gynecology, cardiovascular research, and pharmacy from academic institutions and hospitals in countries such as Denmark, Germany, the United Kingdom, the United States, Japan, Israel, Taiwan, and Singapore. The revision is extensive and covers a broad spectrum of methods while providing the same caliber of authoritative information that made the previous edition so popular. Application oriented, practical, and instructive, this Second Edition will meet the needs of the researchers today, and in years to come.

Firmly established as the leading international reference in this field, Non-Invasive Methods and the Skin broke new ground with its comprehensive coverage of methods used in both clinical and experimental dermatology. Completely revised and updated, containing more than twice as much information, the Second Edition continues the tradition. The authors' thorough research and clear organization make this book a baseline reference for those using noninvasive biophysical methods to study the skin. Arranged by physical modality and structured to provide educational and practical information, the second edition, like its predecessor, will prove to be of value to young researchers and senior scientists alike. The coverage of major evaluation and measurement methods share a consistent format, including scope, sources of error, application, and validity. This edition incorporates 69 revised chapters with more than 90 new chapters covering topics such as computer technique, imaging techniques, skin friction, barrier functions, and more.New chapters provide coverage of: computers, computer techniques, and image analysis imaging techniques, including clinical photography legal situations and guidelines behind instrumental use skin friction barrier functions important new techniques such as in vitro confocal microscopy, OCT, and Raman spectroscopy veterinary/animal research use of methods The truly interdisciplinary, international panel of contributors includes experts from the specialties of dermatology, bioengineering, pathology, manufacturing engineering, medical physics, pharmacology, microbiology, neurology, surgery, obstetrics and gynecology, cardiovascular research, and pharmacy from academic institutions and hospitals in countries such as Denmark, Germany, the United Kingdom, the United States, Japan, Israel, Taiwan, and Singapore. The revision is extensive and covers a broad spectrum of methods while providing the same caliber of authoritative information that made the previous edition so popular. Application oriented, practical, and instructive, this Second Edition will meet the needs of the researchers today, and in years to come.

Melanoma is the most aggressive skin cancer. The specificity and sensitivity of clinical diagnosis varies from around 40% to 80%. Here, we investigated whether the chemical changes in the melanoma tissue detected by Raman spectroscopy and neural networks can be used for diagnostic purposes. Near-infrared Fourier transform Raman spectra were obtained from samples of melanoma (n=22) and other skin tumors that can be clinically confused with melanoma: pigmented nevi (n=41), basal cell carcinoma (n=48), seborrheic keratoses (n=23), and normal skin (n=89). A sensitivity analysis of spectral frequencies used by a neural network was performed to determine the importance of the individual components in the Raman spectra. Visual inspection of the Raman spectra suggested that melanoma could be differentiated from pigmented nevi, basal cell carcinoma, seborrheic keratoses, and normal skin due to the decrease in the intensity of the amide I protein band around 1660 cm-1. Moreover, melanoma and basal cell carcinoma showed an increase in the intensity of the lipid-specific band peaks around 1310 cm-1 and 1330 cm-1, respectively. Band alterations used in the visual inspection were also independently identified by a neural network for melanoma diagnosis. The sensitivity and specificity for diagnosis of melanoma achieved by neural network analysis of Raman spectra were 85% and 99%, respectively. We propose that neural network analysis of near-infrared Fourier transform Raman spectra could provide a novel method for rapid, automated skin cancer diagnosis on unstained skin samples.

Previous biochemical studies demonstrated differences in the structure of lipids in normal skin and psoriatic lesions. Raman spectroscopy provides a unique possibility of studying the molecular structure of proteins, lipids and water in intact skin. Near-infrared Fourier transform Raman spectroscopy was used to study changes in molecular structure and conformation of proteins and lipids of stratum corneum in healthy persons and patients with psoriasis. In vitro Raman spectra were obtained from intact psoriatic scales in 11 patients and from normal stratum corneum of forearm, elbow and heel in a group of age-matched healthy persons. The spectra of stratum corneum differed between psoriasis and normal skin but not between investigated regions. No major changes of lipid band positions in Raman spectra were found, but the crystalline lipid structure was disrupted in psoriatic scales (assessed as the ratio of the symmetric methylene C-H stretching-mode intensities, S(lat)). Major spectral differences were seen in the molecular structure of the proteins. In the spectra of psoriatic scales, the peak position of the amide I band, in comparison with the normal skin, was shifted to higher wavenumbers, suggesting unfolding of proteins. Moreover, alterations in the disulfide stretch bonds of proteins were found in psoriasis scales, resulting in a less energetically favourable gauche-gauche-trans conformation (band around 520 cm(-1)). Psoriatic scales and normal stratum corneum did not statistically differ in their water content. The findings further define the molecular abnormalities in the stratum corneum in psoriasis.

Background. Psoriasis is a common disease in dermatology practice. In USA, 7 million of people (2-3%) have psoriasis. Approximately 5% of the patients with nail psoriasis don't show cutaneous psoriasis and 10-20% of them have psoriatic arthritis. In patients with psoriatic arthritis, 53-86% have nail involvement. Objective. To study the nail changes with high-resolution ultrasound (15MHz). Methods and material. We utilized Philips ATL 5000 ultrasound equipment with SonoCT, XRES, extended field of vision and a linear probe of 15-7 MHZ. We studied 15 patients, 9 healthy control individuals and 6 psoriatic patients with nail involvement, (Women n=9; Men n= 6, Mean age= 47.7 years). All the nails of both hands were observed in both groups (150 nails). We measured in every patient the distance between ventral and dorsal nail plates and also between the ventral plate and the bone margin of the distal phalanx at the right index finger. Results. The normal ultrasound anatomy of the nail in high resolution was described and also the morphological changes in the psoriatic nails that included 4 types of alterations: focal hyperechoic compromise of the ventral plate without involvement of the dorsal plate, loosening of the borders of the ventral plate, wavy plates, and absence of definition of both plates. There was a significant difference (p= 0.02) between the mean distance ventral plate- osseous margin of the distal phalanx in psoriatic patients (3,0 mms) and healthy control individuals (1,5 mm). Conclusion. High resolution ultrasound permits non invasive study of the nail, to describe and measure the morphological characteristics and changes of the nail in healthy control individuals and psoriatic patients, which can be useful for monitoring treatment effects of psoriasis in its different manifestations. Imperceptibles nail changes for the clinician in magnitude and location, can be detected without waiting the whole total replacement of the nail. To our concern the differences of distance between the nail plates including the distance with the bone margin in high resolution ultrasound has not been previously reported.

Sir,Ehlers-Danlos syndrome (EDS) is a rare connectivetissue disease manifested clinically as joint hypermobi-lity, skin hyperextensibility, poor wound healing withabnormal scarring and bruising due to blood vesselfragility (1). The diagnosis of EDS is based on a scoringsystem that requires a time-consuming examination(2, 3). Recently attempts have been made to findadditional minor criteria that may contribute to thediagnosis of EDS (3, 4).We have observed that the hair follicles of the skin inpatients with EDS are macroscopically more prominentthan those of healthy subjects (Fig. 1A, B). To verifythis finding the size of the hair follicles in patientswith EDS was measured by skin ultrasonography.Ultrasonography is an established method for non-invasive investigation of the skin, and the imagesclearly show the epidermal entrance echo, the dermisand the hair follicles (5, 6).PATIENTS AND METHODS

*Chemical Institute, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark Department of Dermatology and Venereology, Motol University Hospital, Vlvalusy Praque, Charles University 2 Medical School, The Czech Republic Department of Pathology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark § Informatics and Mathematical Modelling, Technical University of Denmark, Building 321, 2800 Lyngby, Denmark.

Skin lesion classification based on in vitro Raman spectroscopy is approached using a nonlinear neural network classifier. The classification framework is probabilistic and highly automated. The framework includes a feature extraction for Raman spectra and a fully adaptive and robust feedforward neural network classifier. Moreover, classification rules learned by the neural network may be extracted and evaluated for repro- ducibility, making it possible to explain the class assignment. The classification performance for the present data set, involving 222 cases and five lesion types, was 80.5% 5.3% correct classification of malignant melanoma, which is similar to that of trained der- matologists based on visual inspection. The skin cancer basal cell carcinoma has a classification rate of 95.8% 2.7%, which is excel- lent. The overall classification rate of skin lesions is 94.8% 3.0%. Spectral regions, which are important for network classification, are demonstrated to reproduce. Small distinctive bands in the spectrum, corresponding to specific lipids and proteins, are shown to hold the discriminating information which the network uses to diagnose skin lesions.

Microscopic near-infrared Fourier transform Raman investigations were performed of skin samples from the Nekht-Ankh mummy found in the 'Tomb of the Two Brothers' in Egypt (ca 2000 BC). Spectra were obtained from various sites on the samples. The lipids and proteins seemed well preserved, although different degrees of protein deterioration were observed. In some spots the protein degradation was rather high. Some sites showed very well preserved protein secondary structures with both helical and sheet contents, indicating that the artificial mummification process had a positive effect although no embalming chemicals were left in those spots. Sodium sulphate was the only artificial chemical that could be detected and the degradation of lipid and protein seemed to be rather high in the region containing sodium sulphate. The Raman spectra of the best preserved skin samples from the Nekht-Ankh mummy are very similar to those obtained from the best preserved child rock-cleft mummy (I/2) from Qilakitsoq in Greenland. The conclusion is that the artificial embalming process used by the ancient Egyptians was an efficient way to preserve the mummies even under hot conditions. Copyright (C) 2003 John Wiley Sons, Ltd.