Microdialysis is a minimally invasive technique for chronological study of metabolic, biochemical, and pharmacological events in living tissue. In the skin, probes are placed in the dermis or subcutis for research in two main areas, percutaneous penetration and various aspects of inflammation. Advances in technique, and the concept of data generation and analysis are leading to new areas of application.

Reinoids (vitamin A and its derivatives) are modulators of proliferation and differentiation in a variety of cell types, including epidermal cells. Both retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) can be converted to the acid form retinoic acid (RA) and 3,4-didehydroretinoic acid (ddRA), ligands for the nuclear receptors inducing gene transcriptions. Using high-performance liquid chromatography we have investigated the endogenous ROH and ddROH concentrations and the metabolism of [³H]ROH in cultures of keratinocytes, melanocytes, Hela cells, melanoma cell and two cell lines of non human origin (CV-1 and F9). Cellular retinoid-binding proteins (CRABP I, CRABP II) were also determined by radioligand binding technique and RT-PCR.

Keratinocytes and melanocytes contained high concentrations of ROH and ddROH, Hela- and melanoma cells contained intermediate amounts of retinoids, while in the cell of non human origin only ROH was detected. Analysis of CRABP Il showed a correlation to the cells' ability to accumulate ddROH, suggesting a role for this protein in the 3,4-didehydro metabolic pathway. In melanocytes CRABP I was highly expressed and in melanoma cells CRABP Il dominated. CV-1 and F9 contained low levels of CRABP Il.

Incubation with [³H]ROH for 1-24 hours resulted in a rapid appearance of [3H]ddROH in keratinocytes and toa lesser extent in Hela cells,  melanocytes and melanoma cells. At the end of the incubation the amount of [³H]ddROH corresponded to 30% of the total cellular radioactivity in the Hela cells, 10% in the keratinocytes, 4% in melanocytes and only 1 % in the melanoma cells. The cell types of non human origin did not produce [³H]ddROH from [³H]ROH. These findings support the concept that ddROH production is cell and tissue specific.

Another purpose of this study was to examine the influence of ultraviolet radiation (UVR) on cellular metabolism of retinoids. A physiological dose of UVR reduced the concentration of ROH, ddROH and [³H]RA in cell cultures by 20-50%. The concentration retumed to control levels in about 1-2 days. The uptake of [³H]ROH which was almost 3-fold higher in melanocytes than in keratinocytes, did not much differ between irradiated and control cells. Also, the formation of [³H]ddROH from [³H]ROH was unaffected by UVR. However, the accumulation of the metabolite all-trans [3H]RA was 60% higher in irradiated than unirradiated keratinocytes and melanocytes. Our data indicate that restoration of cellular vitamin A after UVR is mainly accomplished by a retarded metabolism of RA to less active compounds and indicate that the homeostatic control of RA production isa priority after UVR. Failure of this control may be an important factor in UV-induced carcinogenesis in vivo.

SSI:s vetenskapliga UV-råd skall ge myndigheten råd om det vetenskapliga underlaget beträffande sambandet UV-strålning och biologiska effekter. Vidare ligger i uppdraget att ge vägledning inför SSI:s ställningstagande i frågor av policykaraktär. Rådet har under året haft följande ledamöter: docent Harry Beitner, docent Yvonne Brandberg, meteorolog Weine Josefsson, professor Olle Larkö, professor Ulrik Ringborg (ordförande), docent Bernt Lindelöf, professor Per Söderberg, professor Rune Toftgård, docent Johan Hansson och docent Johan Westerdahl. Till rådet har adjungerats myndighetsspecialist Lars-Erik Paulsson.

Alla tre hudcancerformer - malignt melanom, skivepitelcancer och basalcellscancer – ökar i Sverige och internationellt. Gemensamt för alla tre formerna är att ökningen sammanhänger med exposition av solens UV-strålning, den viktigaste yttre riskfaktorn. Av detta följer att modifiering av UV-exposition, framför allt genom ändrade solvanor i befolkningen, bör kunna leda till en minskning av förekomsten av hudcancer. Primär prevention genom förebyggande insatser med syfte minskad UV-exposition, bedöms vara ett betydelsefullt sätt att motverka uppkomsten av alla tre formerna av hudcancer.

Ett annat gemensamt drag hos dessa tre tumörformer är nyttan av tidig diagnostik. Ett tidigt avlägsnande av en hudcancer innebär mindre sjukvårdsinsatser och, för framför allt malignt melanom, minskad risk för tumörspridning. Tumörutvecklingen sker ofta via förstadier och ökad kunskap om dessa leder till möjligheter att avlägsna förstadier innan dessa har hunnit bli elakartade tumörer. Denna form av tidigdiagnostik gränsar till den primära preventionen.

Av de tre formerna hudcancer är det i första hand malignt melanom som kan förorsaka död i sjukdomen. Ett väsentligt mål med förebyggande insatser är därför att minska dödligheten. För alla tre formerna kan insjuknande förorsaka betydande besvär för patienten. På grund av den rikliga förekomsten av maligna hudtumörer är sjukvårdskostnader betydande. Därför är mål för förebyggande insatser också minskad morbiditet och sjukvårdskostnader. Förutom hudcancer orsakar solens UV-strålning betydande problem i form av ögonskador.

I årets rapport redovisas (1) epidemiologiska aspekter av malignt hudmelanom, som under senare år uppvisar en stegrad ökningstakt; (2) maligna melanom hos barn och ungdomar; (3) förslag till studier av skivepitelcancer och yrke; (4) förekomst och kostnader för medicinsk handläggning av patienter med basalcellscancer, som visar höga incidenssiffror och höga kostnader; (5) lymfom och UV-strålning; (6) UV-strålning och katarakt, betydelsefullt med förebyggande åtgärder; (7) förslag till workshop om cellulära effekter av UV-strålning; (8) rekommendation att använda den uppgraderade versionen av European Code Against Cancer; (9) UV-strålning och vitamin D, viss UV-dos är av nytta; (10) dosrat och fraktioner av UV-strålning i relation till utveckling av hudcancer och hos möss, påverkar ej preventiva strategier; (11) debatt om ökad solexposition eventuellt skulle leda till förbättrad överlevnad för melanompatienter ändrar ej preventiva strategier; (12) synpunkter på primär prevention från 6th World Conference on Melanoma, Vancouver, 2005.

Polymorphisms of GSTM1, GSTT1 and GSTP1 were examined in melanoma patients and tumor-free individuals. Relationships between the polymorphisms and tumor characteristics and pigment phenotypes of the patients were analyzed. There was no significant difference in GSTM1 null and GSTT1 null genotypes nor GSTP1 GG genotype between melanoma patients and controls. In melanoma patients, these polymorphisms were not correlated with early or later onset of melanomas or gender of the patients. Frequency of GSTM1 null genotype was higher in patients with melanoma >2.5 mm than in those with tumors <1.0 mm, and higher frequency was found in nodular melanoma than in the other tumor types. GSTP1 GG genotype was more often found in the patients with brown and mixed eye color or brown and black hair than those with blue and green eyes or blond hair. It is unlikely that polymorphisms of GSTM1, GSTT1 and GSTP1 are general risk factors for melanoma in the Swedish population. GSTM1 null genotype was correlated with Breslow thickness and tumor type, which might serve as an additional biomarker for a rapid tumor progression. GSTP1 GG increases risk for melanoma in the subgroup of individuals with dark eyes or hair.

Skin behaves as a viscoelastic material, having mechanical properties composed of elastic and fluid components. Upon indentation, the fibres are stretched and fluid displaced from the compressed region. The rate of recovery from this imprint is therefore dependent on the hydration and elasticity of the skin. A reliable measurement could be applied to the assessment of clinical conditions such as oedema, rare genetic disorders such as cutis laxa  and the evaluation of the 'effective age' of skin in vivo . This paper describes a new approach to the non-invasive indentation technique and a novel method of analysis. A method is proposed that tracks the skin's recovery optically from an initial strain made using a mechanical indentor, diffuse side-lighting and a CCD video-capture device. Using the blue colour plane of the image it is possible to examine the surface topography only, and track the decay of the imprint over time. Two algorithms are discussed for the extraction of information on the skin's displacement and are analysed in terms of reliability and reproducibility.

Skin behaves as a viscoelastic material, having mechanical properties composed of elastic and fluid components. Upon indentation, the fibres are stretched and fluid displaced from the compressed region. The rate of recovery from this imprint is therefore dependent on the hydration and elasticity of the skin. A reliable measurement could be applied to the assessment of clinical conditions such as oedema, rare genetic disorders such as cutis laxa and the evaluation of the 'effective age' of skin in vivo . This paper describes a new approach to the non-invasive indentation technique and a novel method of analysis. A method is proposed that tracks the skin's recovery optically from an initial strain made using a mechanical indentor, diffuse side-lighting and a CCD video-capture device. Using the blue colour plane of the image it is possible to examine the surface topography only, and track the decay of the imprint over time. Two algorithms are discussed for the extraction of information on the skin's displacement and are analysed in terms of reliability and reproducibility.

The performance of Roche polymerase chain reaction (PCR) Amplicor to detect Chlamydia trachomatis in first-voided urine specimens from 422 males and 456 females attending two clinics for sexually transmitted infections was evaluated in comparison with cultures of urethral and cervical specimens. At the same time, the ability of leucocyte esterase (LE) in first-voided urine and the presence of leucocytes in urethral and cervical smears to identify C. trachomatis -infected individuals based on PCR and culture was determined. The prevalence of C. trachomatis infection was 10.9 % in men and 7.7 % in women. Sensitivity, specificity, positive predictive value and negative predictive value of Amplicor was 93.5 %, 99.7 %, 97.7 % and 99.2 % in males and 91.4 %, 99.5 %, 94.1 % and 99.3 % in females. All Chlamydia-infected men were identified by means of a combination of urethritis (≥4 leucocytes in the urethral smear) and/or a positive LE test in urine, although the specificity was only 42.2 %. In women, the combination of urethritis and/or cervicitis and/or a positive LE test identified 85.7 % of Chlamydia-infected patients with a specificity of 38.2 %. It is concluded that a combination of urethral and/or cervical smears and LE testing of urine can be used as a screening test to select patients, especially males, for specific C. trachomatis testing.

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 × 105/mL) were cultured with or without 3 μM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 ± 3.9% in HNE1-LMP1 cells vs 37.89 ± 4.9% in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 ± 3.5 vs 65.87 ± 5.9%), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 ± 3.7 and 27.91 ± 2.1%), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 ± 3.9 vs 29.19 ± 6.27%) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3. © 2006 Brazilian Journal of Medical and Biological Research.

The aim of this study was to compare conventional 16S rRNA gene PCR, real-time 16S rRNA gene PCR and real-time Mycoplasma genitalium adhesin protein (MgPa) gene PCR as detection methods for M. genitalium infection. The study also determined the prevalence of M. genitalium in male and female patients attending a sexually transmitted infections clinic in a rural area in the west of Sweden. First void urine (FVU) and/or urethral swabs were collected from 381 men, and FVU and/or cervical swabs and/or urethral swabs were collected from 298 women. A total of 213 specimens were used in the PCR comparative study: 98 consecutively sampled specimens from patients enrolled in the prevalence study, 36 consecutively sampled specimens from patients with symptoms of urethritis and 79 specimens from patients positive for M. genitalium by real-time MgPa gene PCR in the prevalence study. A true-positive M. genitalium DNA specimen was defined as either a specimen positive in any two PCR assays or a specimen whose PCR product was verified by DNA sequencing. The prevalence of M. genitalium infection in men and women was 27/381 (7.1 %) and 23/298 (7.7 %), respectively. In the PCR comparative study, M. genitalium DNA was detected in 61/76 (80.3 %) of true-positive specimens by conventional 16S rRNA gene PCR, in 52/76 (68.4 %) by real-time 16S rRNA gene PCR and in 74/76 (97.4 %) by real-time MgPa gene PCR. Real-time MgPa gene PCR thus had higher sensitivity compared with conventional 16S rRNA gene PCR and had considerably increased sensitivity compared with real-time 16S rRNA gene PCR for detection of M. genitalium DNA. Real-time MgPa gene PCR is well suited for the clinical diagnosis of M. genitalium.

Background: Although photodynamic therapy (PDT) is becoming an important treatment method for skin lesions such as actinic keratosis (AK) and superficial basal cell carcinoma, there are still discussions about which fluence rate and light dose are preferable. Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates. However, these results have not yet been verified in humans. Objectives: The objective was to investigate the impact of fluence rate and spectral range on primary treatment outcome and bleaching rate in AK using aminolaevulinic acid PDT. In addition, the pain experienced by the patients has been monitored during treatment. Patients/methods Thirty-seven patients (mean age 71 years) with AK located on the head, neck and upper chest were treated with PDT, randomly allocated to four groups: two groups with narrow filter (580-650 nm) and fluence rates of 30 or 45 mW cm-2, and two groups with broad filter (580-690 nm) and fluence rates of 50 or 75 mW cm-2. The total cumulative light dose was 100 J cm-2 in all treatments. Photobleaching was monitored by fluorescence imaging, and pain experienced by the patients was registered by using a visual analogue scale graded from 0 (no pain) to 10 (unbearable pain). The primary treatment outcome was evaluated at a follow-up visit after 7 weeks. Results: Our data showed a significant correlation between fluence rate and initial treatment outcome, where lower fluence rate resulted in favourable treatment response. Moreover, the photo-bleaching dose (1/e) was found to be related to fluence rate, ranging from 4.5 ± 1.0 J cm -2 at 30 mW cm-2, to 7.3 ± 0.7 J cm-2 at 75 mW cm-2, indicating higher oxygen levels in tissue at lower fluence rates. After a cumulative light dose of 40 J cm-2 no further photobleaching took place, implying that higher doses are excessive. No significant difference in pain experienced by the patients during PDT was observed in varying the fluence rate from 30 to 75 mW cm-2. However, the pain was found to be most intense up to a cumulative light dose of 20 J cm-2. Conclusions: Our results imply that the photobleaching rate and primary treatment outcome are dependent on fluence rate, and that a low fluence rate (30 mW cm-2) seems preferable when performing PDT of AK using noncoherent light sources.

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.

Object. The aim of this study was to make a preliminary evaluation of whether microdialysis monitoring of cytokines and other proteins in severely diseased neurosurgical patients has the potential of adding significant information to optimize care, thus broadening the understanding of the function of these molecules in brain injury. Methods. Paired intracerebral microdialysis catheters with high-cutoff membranes were inserted in 14 comatose patients who had been treated in a neurosurgical intensive care unit following subarachnoidal hemorrhage or traumatic brain injury. Samples were collected every 6 hours (for up to 7 days) and were analyzed at bedside for routine metabolites and later in the laboratory for interleukin (IL)-1 and IL-6, in two patients, vascular endothelial growth factor and cathepsin-D were also checked. Aggregated microprobe data gave rough estimations of profound focal cytokine responses related to morphological tissue injury and to anaerobic metabolism that were not evident from the concomitantly collected cerebrospinal fluid data. Data regarding tissue with no macroscopic evidence of injury demonstrated that IL release not only is elicited in severely compromised tissue but also may be a general phenomenon in brains subjected to stress. Macroscopic tissue injury was strongly linked to IL-6 but not IL-1b activation. Furthermore, IL release seems to be stimulated by local ischemia. The basal tissue concentration level of IL-1b was estimated in the range of 10 to 150 pg/ml, for IL-6, the corresponding figure was 1000 to 20,000 pg/ml. Conclusions. Data in the present study indicate that catheters with high-cutoff membranes have the potential of expanding microdialysis to the study of protein chemistry as a routine bedside method in neurointensive care.

In vivo diagnostics of skin diseases as well as understanding of the skin biology constitute a field demanding characterization of physiological and anatomical parameters. Biomedical optics has been successfully used, to qualitatively and quantitatively estimate the microcirculatory conditions of superficial skin. Capillaroscopy, laser Doppler techniques and spectroscopy, all elucidate different aspects of microcirculation, e.g. capillary anatomy and distribution, tissue perfusion and hemoglobin oxygenation. We demonstrate the use of a diffuse reflectance hyperspectral imaging system for spatial and temporal characterization of tissue oxygenation, important to skin viability. The system comprises: light source, liquid crystal tunable filter, camera objective, CCD camera, and the decomposition of the spectral signature into relative amounts of oxy- and deoxygenized hemoglobin as well as melanin in every pixel resulting in tissue chromophore images. To validate the system, we used a phototesting model, creating a graded inflammatory response of a known geometry, in order to evaluate the ability to register spatially resolved reflectance spectra. The obtained results demonstrate the possibility to describe the UV inflammatory response by calculating the change in tissue oxygen level, intimately connected to a tissue's metabolism. Preliminary results on the estimation of melanin content are also presented.

Uremisk klåda är ett stort problem hos patienter med avancerad njursvikt. En enkätstudie på dialyspatienter visade att omfattningen av problemet var större än förväntat. Att tillfredställande behandla uremisk klåda är svårt och många olika behandlingsalternativ finns. Den enda behandlingen som är riktigt effektiv är njurtransplantation.

Background: There is a strong correlation between naevus number and prospective melanoma risk. Melanoma is one of the most rapidly increasing cancers in Estonia and primary prevention programmes for melanoma that target risk behaviour in the sun have so far not been launched. Methods: The naevus profile was examined in 549/700 9-year-old Estonian children (282 boys and 267 girls) and the presence of active atopic dermatitis (AD) was registered. Results: There was a wide range of naevi (4-121) and a median total body count of 26. There was no difference in naevus count between boys and girls. No dysplastic naevi were found. Thirty-nine of 549 children (7%) had at least one lesion clinically diagnosed as a congenital naevus. Boys had more naevi on the face (median 4) and trunk (median 12) than girls (median 3 and 9, respectively, P < 0.001). Girls had more naevi on the legs compared with boys (median 4 and 3, respectively, P < 0.01). Fifty-four out of 549 (9.8%) had naevi on the palms and 18/549 (3.3%) on the soles. Children with fair skin, freckles and light hair and eye colours had significantly more naevi than those with darker colours. Thirty-one of 549 (6%) children had AD diagnosed on the examination day and they had a lower total naevus count (median 20) compared with children with no AD (median 27,n = 518, P < 0.05). Conclusions: The naevus situation in Estonian children today might constitute a starting point for evaluating the efficiency of coming preventive measures as a change of naevus number in children might serve as an early marker for a change in melanoma incidence. © 2006 European Academy of Dermatology and Venereology.

Effectively co-ordinated treatment support from healthcare providers (doctors, nurses and pharmacists) may improve patients' adherence to treatment. The objective of this study was to identify patients' and providers' perceptions of the roles of different Healthcare providers in dermatological treatment. Focus groups were used in two types of fora: patients with chronic dermatological diseases (n =2×6) and healthcare providers (n =2×6), including doctors, nurses and pharmacists working in dermatological care. Data were analysed according to the Consensual Qualitative Research approach. The respondents viewed the roles of the providers as complementary, but poorly co-ordinated. Treatment support is provided mainly by the nurse. During the doctor's appointment, diagnosis and treatment decisions are often prioritized, leaving limited time for treatment support. The pharmacist's provision of support is constrained by the lack of privacy and clinical history of individual patients. The most apparent "gap" in the chain of treatment support was between the pharmacist and the other providers. There was a wish for improved interprofessional collaboration to avoid giving conflicting advice. There is a need to improve interprofessional collaboration in dermatology, in order to optimize treatment support in clinical practice.

Adherence to long-term therapy for chronic illness is on average 50%. However, regarding adherence to dermatological treatment the existing literature is limited. The aim of the study was to acquire an understanding of issues associated with adherence to dermatological therapy. Focus group interviews were used in two types of fora: patients with chronic dermatological diseases and health care providers, including doctors, nurses and pharmacists working in dermatological care. Results reveal the providers' view of a suboptimal rate of adherence. According to both providers and patients, factors affecting adherence were patients' expectations and experiences of therapeutic effect, possibilities for the patient to take active part in treatment decisions, as well as mode of administration and type of medication. Suggested strategies for improvement are individualized patient education, continuous treatment support with assessment of medication-taking behaviour and enhanced communication skills among the providers.

Background/aims: In vivo confocal laser scanning microscopy (CLSM) is a new method for high-resolution imaging of intact skin in situ. Horizontal mapping of the outer skin is provided (magnification × 1000). Objectives: Tattooing is popular all over the world, however, tattooed skin has not been studied in using CLSM. Results: Tattoos in two volunteers were studied using the Vivascope1500® of Lucid Inc. Subepidermal massive deposits of dense, clustered pigment granules up to about 3 μm in size corresponding to black tattoos, and more scarce and diffuse deposits, corresponding to red, blue and green tattoos, were observed. Diffuse pigment granules tended to accumulate in the outer dermis underneath the level of the basement membrane zone. Conclusion: Dermal pigments from tattoos can be imaged in vivo using CLSM. This application of CLSM has an important future potential for pre-evaluation of tattoos before laser removal, predicting good or poor outcome of laser removal. Copyright © Blackwell Munksgaard 2006.

Purpose: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Methods and Materials: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy. Results: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p ≤ 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. Conclusion: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors. © 2005 Elsevier Inc.

Photodynamic therapy (PDT) is an efficient treatment for actinic keratosis. A common problem, however, is pain. The aim of this study was to investigate pain during PDT for actinic keratosis. The possibility of using capsaicin cream for pain relief was also assessed. Pain was investigated during aminolaevulinic acid PDT in 91 patients. Size, redness, scaling and induration of the lesions were recorded. Maximum pain during treatment was registered, using a visual analogue scale (0-10). The pain-reducing efficacy of capsaicin was tested in a pilot study in six patients (10 lesions). These patients were pre-treated with capsaicin cream for one week before commencing PDT. Pain was found to be normally distributed around a mean value of visual analogue scale 4.6. Larger lesions gave more pain (p=0.001). The redness of the actinic lesions was found to be related to PDT-induced pain (p=0.01), the reduction of actinic area (p=0.007), and the cure rate (p=0.01). The redder the actinic area, the better the treatment outcome and the more pain experienced. Patients with the largest reduction in the actinic area experienced more pain (p=0.053). The most important factors for presence of pain seem to be the size and the redness of the lesion. No significant pain relief was experienced after pre-treatment with capsaicin. © 2006 Acta Dermato-Venereologica.

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 methodsThe 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.

Creams, ointments and solutions applied to the skin surface by patients as part of a daily routine might be expected to provide a more variable dosage than do standard tablets. However, adherence to treatment in dermatology has been little studied. This article reviews recent publications in the field. These are dominated by questionnaire-based studies, which tend to over-estimate adherence. Reduced adherence to dermatological treatment is noted in 34-45% of patients. It is likely that the percentage of patients who practice truly optimal treatment in their daily life is even lower considering the variable practice of self-treatment. Self-reported psychiatric morbidity contributes to poor adherence to dermatological treatment, while a well-functioning doctor-patient interaction is a major determinant of good adherence, as is patient satisfaction. In conclusion, adherence to dermatological treatment is unsatisfactory and there is a need for intervention and change in clinical routines. The therapeutic and economic benefits may be considerable. The immediate challenge is to stimulate a change in patient behaviour and improve self-treatment at home. © 2006 Acta Dermato-Venereologica.

Background/aims: Fibre-optic confocal imaging in vivo is a new approach in the assessment of human skin. The objective is to describe a novel instrument and its operation and use in combination with fluorophores. Methods: The Stratum® is a fibre-optic fluorescence confocal microscope especially developed for the study of skin and mucous membranes. The system is flexible and any body site can be studied with a hand-held scanner. The light source is a 488 nm argon ion laser. Horizontal (en face) images of the epidermis and outer dermis are produced with cellular resolution. Magnification is approximately 1000x. Fluorescein sodium is routinely used as fluorophore (intradermal injection or application to the skin surface). This fluorophore is safe for human use in vivo, but other substances (rhodamine B, Acridine Orange, green fluorescent protein, curcumin) have also been studied. Results: The instrument produces sharp images of epidermal cell layers from the epidermal surface to the sub-papillary dermis, with sub-cellular resolution. The scanner is flexible in use. The technique of intradermal fluorophore injection requires some skill. Conclusions: We consider this fibre-optic instrument a potentially important tool in skin research for non-invasive optical biopsy of primarily the epidermis. Present use is focussed on research applications, where the fluorophore distribution in the skin may illustrate morphological changes in the epidermis. © Blackwell Munksgaard, 2005.

Aim: To examine whether polymorphisms in SULT1A1 and GSTP1 genes contribute to colorectal cancer development and whether they are associated with clinicopathological variables are not well identified. Methods: We examined the genotypes of 125 colorectal cancer patients and 666 healthy controls in a Swedish population by using PCR restriction fragment length polymorphism (RFLP). Results: SULT1A1 *2/*2 genotype (OR = 2.49, 95%CI = 1.48-4.19, P = 0.0002) and *2 allele (OR = 1.56, 95%CI = 1.16-2.10, P = 0.002) had an effect on colorectal cancer susceptibility, while GSTP1 genotype was without effect. However, GSTP1 G-type predicted a worse prognosis in the patients independently of gender, age, Dukes' stage, growth pattern, and differentiation (P = 0.03). Conclusion: Polymorphism in SULT1A1 may predispose to colorectal cancer and GSTP1 may be a biological indicator of prognosis in the patients. © 2005 The WJG Press and Elsevier Inc. All rights reserved.

Cancer research has mainly focused on alterations of genes and proteins in cancer cells themselves that result in either gain-of-function in oncogenes or loss-of-function in tumour-suppressor genes. However, stromal variables within or around tumours, including blood and lymph vessels, stromal cells and various proteins, have also important impacts on tumour development and progression. It has been shown that disruption of stromal-epithelial interactions influences cellular proliferation, differentiation, death, motility, genomic integrity, angiogenesis, and other phenotypes in various tissues. Moreover, stromal variables are also critical to therapy in cancer patients. In this review, we mainly focus on the clinicopathological significance of stromal variables including angiogenesis, lymphangiogenesis, inflammatory infiltration, matrix metalloproteinase (MMP), and the particularly interesting new cysteine-histidine rich protein (PINCH) in colorectal cancer (CRC). © 2006 Sun and Zhang, licensee BioMed Central Ltd.

Nuclear factor-κB (NF-κB) is responsible for the expression by regulating many genes for immune response, cell adhesion, differentiation, proliferation, angiogenesis and apoptosis. The function of NF-κB is inhibited by binding to NF-κB inhibitor (IκB), and imbalance of NF-κB and IκB has been associated with development of many diseases, including tumours. In this review, we focus on polymorphisms of the NFKB and NFKBI genes in relation to development of common inflammatory diseases including ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, giant cell arthritis, type 1 diabetes, multiple sclerosis, celiac disease, and Parkinson's disease, as well as susceptibility of several cancers, such as oral squamous cell carcinoma, colorectal cancer (CRC), hepatocellular carcinoma, breast cancer and myeloma.

Objective: To investigate the effects of atopic diseases on nevus development during childhood. Design: A descriptive survey of nevi in a cohort of 8- and 9-year-old children combining a skin examination and a validated questionnaire regarding atopic dermatitis, allergic rhinoconjunctivitis, and bronchial asthma. Setting: Fifty-one primary schools in Sweden. Participants: A total of 788 children born in 1992 participated in 1999 in a prevalence study of allergic diseases. The present study was restricted to the 545 children from that study who were still living in the community, and 515 (94%) of them participated. The cumulative incidence of atopic dermatitis, allergic rhino-conjunctivitis, and bronchial asthma was 24%, 12%, and 13%, respectively, from birth to age 7 years as reported by questionnaire, 3% reported all 3 diagnoses. Results: Children with reported atopic dermatitis and findings of active dermatitis on examination had fewer nevi (median, 4, mean, 7.4) than children with no reported atopic disease and no active dermatitis found on examination (median, 9, mean, 11.2) (P<.001). Children who developed active atopic dermatitis after the questionnaire was filled out (ie, during the last 2 years) had fewer nevi than children with no atopic disease (median, 3, mean, 5.3) (P<.001). There was no difference in nevus number between the children with bronchial asthma or allergic rhinoconjunctivitis and children with no atopic disease. Conclusion: Children with atopic dermatitis had few melanocytic nevi, which suggests that the proinflammatory cytokine network in the atopic skin might inhibit melanocyte growth and/or progression to nevi.

The naevus profile was examined in a Swedish cohort of 8-9-year-old children, 524/545 individuals (96%) were examined (279 boys and 245 girls). There was a wide variation in the total number of naevi (0-79) and boys had more naevi than girls (median 9 and 7, respectively, p<0.01). No dysplastic naevi were found. Overall, 15/524 (3%) had at least one lesion clinically diagnosed as a congenital melanocytic naevus. Boys had more naevi on the face (median 1) and trunk (median 5) than girls (median 0 and 3, respectively, p<0.001). There was no difference in the number of naevi on the legs between the two sexes. The highest counts per unit surface area for both sexes were found on the back, chest and the lateral aspect of the arms, areas intermittently sun-exposed. Children with fair skin and light eye colours had significantly more naevi than those with darker colours but children with red hair had very few naevi. Children with one or more naevi on the buttocks (25%), dorsal surfaces of the feet (11%) or on the scalp (7%) had twice as many naevi in total compared with those without naevi in these regions. Children with naevi in all three regions (0.8%) had four times as many naevi in total. A relationship between total counts and counts on the back or lateral aspect of the arms was found (r2=0.59). Either of these two areas might be suitable for predicting total naevus counts.

Photodynamic therapy (PDT) with topical methyl aminolevulinate (MAL) administered in two treatment sessions separated by 1 week is an effective treatment for actinic keratoses. This open prospective study compared the efficacy and safety of MAL-PDT given as a single treatment with two treatments of MAL-PDT 1 week apart. Two hundred and eleven patients with 413 thin to moderately thick actinic keratoses were randomized to either a single treatment with PDT using topical MAL (regimen I, n=105) or two treatments 1 week apart (regimen II, n=106). Each treatment involved surface debridement, application of Metvix® cream (160 mg/g) for 3 h, followed by illumination with red light using a light-emitting diode system (peak wavelength 634±3 nm, light dose 37 J/cm2). Thirty-seven lesions (19%) with a non-complete response 3 months after a single treatment were re-treated. All patients were followed up 3 months after the last treatment. A total of 400 lesions, 198 initially treated once and 202 treated twice, were evaluable. Complete response rate for thin lesions after a single treatment was 93% (95% CI=87-97%), which was similar to 89% (82-96%) after repeated treatment. Response rates were lower after single treatment of thicker lesions (70% (60-78%) vs 84% (77-91%)), but improved after repeated treatment (88% (82-94%)). The conclusion of this study is that single treatment with topical MAL-PDT is effective for thin actinic keratosis lesions, however, repeated treatment is recommended for thicker or non-responding lesions. © 2005 Taylor & Francis.

Skin cancer is one of the most rapidly increasing cancers among the Swedish population and a significant cause of illness and death. The aim of this study was to from a societal perspective estimate the total cost of skin cancer in Sweden in 2005, using a combined top-down and bottom- up, prevalence based cost of illness approach. The total cost of skin cancer was estimated to 1,25 billion SEK (1 €= 9,3 SEK). The direct costs were estimated to 665 million SEK and constituted 53 percent of the total cost. Indirect costs were estimated to 583 million SEK and constituted 47 percent of the total cost. The main cost driver was production lost caused by premature death, amounting to 39 percent of the total cost.

In addition, this study compares the cost of skin cancer with the costs arising from road traffic accidents. Focusing on the methodological differences that arise when comparing economic cost founded on similar but yet different methods when conducting cost analysis. We demonstrate that the seemingly large difference between the cost of skin cancer and the cost arising from road traffic accident, in reality is not as large as it first appear.