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The skin mirrors the individual's well being. Visible for both the patient and the attending physician, it can be a source of information for the diagnosis of multi-system diseases and diseases of internal organs. Therapy is usually directed at the primary disease. Pharmaco-therapeutic options for internal diseases are at present not always optimal and specific management of side effects of drugs with vital indication may be necessary. Better understanding of the mechanisms of the cutaneous manifestations may help develop more efficacious, better tolerated therapy and improve the patient's situation.

Microdialysis enables in vivo sampling of endogenous and exogenous substances in the interstitial fluid. A probe equipped with a tubular semi-permeable dialysis membrane is inserted into the skin, and perfused with a physiological solution. Diffusion of molecules from the extracellular space to the perfusate takes place, and the perfusate is collected for analysis. In this thesis, experimental and clinical applications of human cutaneous microdialysis in the fields of skin inflammation and percutaneous absorption are presented.

The in vivo absorption kinetics of the model solvents ethanol and isopropanol, applied in excess to the skin over the dialysis probe, could be demonstrated in all subjects. Ethanol levels increased in a linear fashion to reach a peak at about 100 min, then establishing a plateau level. Isopropanol absorption showed similar kinetics. The absolute levels detected were lower for isopropanol than for ethanol.

Laser Doppler perfusion imaging visualized the skin circulatory response to the microdialysis probe insertion. An immediate increase in skin blood perfusion was observed. The response began to subside after 15 min and returned to near normal within 60 min after probe insertion.

Histamine, a ubiquitous inflammatory mediator, was studied as a model. Following the skin trauma caused by probe insertion, peak histamine levels were observed in the first 10-min sample, then falling successively to reach baseline within 40-60 min. Multiple regression analysis did not reveal any correlation between probe depth, as measured by ultrasoundtechnique, and obtained histamine levels during the equilibration period following probe insertion. Provocation with compound 48/80 as a positive control for skin histamine release, resulted in increased histamine levels in the perfusate. Histamine release was followed in reactions provoked in the skin of patients with cold urticaria. An up to 80-fold increase of histamine levels was observed, with peak levels 20-30 min after start of ice provocation, returning to baseline within 50-60 min.

Human, in vivo, cutaneous microdialysis has the potential to be an important sampling method in studies of skin inflammation and percutaneous absorption of noxious chemicals as well as in dennal and transdermal drug delivery studies.

Chronic painful wounds, a major health problem, have a detrimental impact on the quality of life due to associated pain. Some clinical reports have suggested that local administration of morphine could be beneficial. The aim of this study was to evaluate the analgesic effect of topically applied morphine on chronic painful leg ulcers. Twenty-one patients were randomly assigned to receive either morphine or placebo in a randomised, placebo-controlled, crossover pilot study. Each patient was treated four times in total. Pain was measured by the visual analogue score (VAS) before application of gel, directly after and after 2, 6, 12 and 24 hours. Although an overall, clinically relevant, reduction of pain was observed upon treatment with morphine, the difference was not statistically significant. Morphine reduced pain scores more than placebo on treatment occasions 1 and 2. The difference was statistically significant only 2 hours after dressing on the first treatment occasion. Thus, our study did not demonstrate a consistent and globally significant difference in nociception in patients treated with morphine. However, the relatively small number of patients included in our study and other methodological limitations makes it difficult for us to draw general conclusions regarding efficacy of topically applied morphine as an effective treatment for some painful ulcers. Further studies are warranted to evaluate the value of topically applied morphine in the treatment of patients with chronic painful leg ulcers.

Malignant melanoma arises from the pigment producing melanocytes in epidermis and is the most aggressive type of skin cancer. The incidence of malignant melanoma is increasing faster than any other type of cancer in white population worldwide, with a doubling rate every 10-20 years. So far, the only identified external risk factor for malignant melanoma is UV exposure. Elimination of photodamaged cells by apoptosis (programmed cell death) is essential to prevent tumor formation. Melanocytes are considered relatively resistant to apoptosis, however, the regulation of apoptosis in melanocytes is still unknown.

The aim of this thesis was to investigate the apoptotic process following ultraviolet (UV) irradiation in primary cultures of human melanocytes. Focus was on regulation of mitochondrial stability by Bcl-2 family proteins and the possible participation of lysosomal proteases, cathepsins. UV irradiation activated the mitochondrial pathway of apoptosis, leading to cytochrome c release, caspase activation, and nuclear fragmentation. No change in protein expression of Bax and Bcl-2 was observed in response to UV. Instead, translocation of the Bcl-2 family proteins from cytosol to mitochondia was important in the regulation of survival and death of melanocytes. The findings further demonstrated permeabilization of the lysosomal membrane to occur early in the apoptotic process, resulting in cathepsin release into the cytosol. The cathepsins were potent pro-apoptotic mediators and triggered apoptosis upstream of Bax translocation and mitochondrial membrane permeabilization. In response to both heat and UV irradiation, there was a marked increase in expression of stress-induced heat shock protein 70 (Hsp70), which inhibited apoptosis by binding lysosomal and mitochondrial membranes and counteracting the release of cathepsins and cytochrome c. Furthermore, UV irradiation activated c-jun N-terminal kinase (JNK), which triggered apoptosis upstream of cathepsins release from the lysosomes. In addition, JNK mediated apoptosis through phosphorylation of pro-apoptotic Bim, which was released from anti-apoptotic Mcl-1, by UV induced Mcl-1 depletion.

This thesis illustrates that permeabilization of mitochondria and lysosomes and release of their constituents to the cytosol participates in UV induced apoptosis signaling in human melanocytes in vitro. The process is regulated by a complex network of pro- and anti-apoptotic proteins, exerting their effects through intracellular translocation and alteration of protein expression.

[No abstract available]

Apoptosis and alterations in Bcl-2 and Bax messenger RNA (mRNA) and protein expression were examined in cultured human epidermal melanocytes following UVB irradiation (50 mJ/cm2). The effects of various spectral ranges within UVB were investigated. A co-culture system was set up to study the interplay between melanocytes and keratinocytes in response to UVB. Melanocytes expressed high basal levels of the anti-apoptotic protein Bcl-2 compared with keratinocytes. Different wavelengths within the UVB spectrum induced diverse response patterns of Bcl-2 and Bax mRNA and had different apoptotic power. Both Bcl-2 and Bax mRNA were upregulated to preserve protein levels and only a slight increase in apoptosis was noted 24 h after UVB ([lambda]>305 nm). Increasing UVB between 280 and 305 nm enhanced apoptosis and upregulated Bcl-2, whilst Bax mRNA was unaltered. However, no change in protein levels was detected. A redistribution of Bax protein from different compartments within the cell may be more important than direct upregulation for the acceleration of apoptosis, but it cannot be excluded that other apoptotic pathways may be induced by shorter UVB wavelengths. The increase in apoptosis was significantly lower in melanocytes co-cultured with irradiated matched keratinocytes than in melanocytes from pure cultures, indicating that melanocytes are protected from UVB-induced apoptosis by the release of substance(s) from keratinocytes. This rescue response concurred with a fast and significant increase in Bcl-2 mRNA level in melanocytes.

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Stress-induced heat shock protein 70 (Hsp70) effectively protects cells against apoptosis, although the anti-apoptotic mechanism is still undefined. Exposure of human melanocytes to heat and subsequent UVB irradiation increased the level of Hsp70 and pre-heating reduced UVB induced apoptosis. Immunofluorescence staining of Hsp70 in combination with staining of lysosomes (Lamp2) or mitochondria (Mitotracker^®) in pre-heated UVB exposed cells showed co-localization of Hsp70 with both lysosomes and mitochondria in the surviving cell population. Furthermore, UVB induced apoptosis was accompanied by lysosomal and mitochondrial membrane permeabilization, detected as release of cathepsin D and cytochrome c, respectively, which were prevented by heat pre-treatment. In purified fractions of lysosomes and mitochondria, recombinant Hsp70 attached to both lysosomal and mitochondrial membranes. Moreover, in apoptotic cells Bax was translocated from a diffuse cytosolic location into punctate mitochondrial-like structures, which was inhibited by Hsp70 induction. Such inhibition of Bax translocation was abolished by transfection with Hsp70 siRNA. Furthermore, Hsp70 siRNA eliminated the apoptosis preventive effect observed after pre-heating. These findings show Hsp70 to rescue melanocytes from UVB induced apoptosis by preventing release of cathepsins from lysosomes, Bax translocation and cytochrome c release from mitochondria.

Abbreviations: AIF, apoptosis-inducing factor; Hsp, heat shock protein; NAG, ß-N-acetylglucosaminidase; tBid, truncated Bid; UV, ultraviolet

We demonstrate UVA/B to induce apoptosis in human melanocytes through the mitochondrial pathway, displaying cytochrome c release, caspase-3 activation, and fragmentation of nuclei. The outcome of a death signal depends on the balance between positive and negative apoptotic regulators, such as members of the Bcl-2 protein family. Apoptotic melanocytes, containing fragmented nucleus, show translocation of the proapoptotic proteins Bax and Bid from the cytosol to punctate mitochondrial-like structures. Bcl-2, generally thought to be attached only to membranes, was in melanocytes localized in the cytosol as well. In the fraction of surviving melanocytes, that is, cells with morphologically unchanged nucleus, the antiapoptotic proteins Bcl-2 and Bcl-X_L were translocated to mitochondria following UVA/B. The lysosomal proteases, cathepsin B and D, which may act as proapoptotic mediators, were released from lysosomes to the cytosol after UVA/B exposure. Proapoptotic action of the cytosolic cathepsins was confirmed by microinjection of cathepsin B, which induced nuclear fragmentation. Bax translocation and apoptosis were markedly reduced in melanocytes after pretreatment with either cysteine or aspartic cathepsin inhibitors. No initial caspase-8 activity was detected, excluding involvement of the death receptor pathway. Altogether, our results emphasize translocation of Bcl-2 family proteins to have central regulatory functions of UV-induced apoptosis in melanocytes and suggest cathepsins to be proapoptotic mediators operating upstream of Bax.

UVB irradiation induced phosphorylation of JNK and subsequent apoptosis in human melanocytes. Depletion of both JNK1 and JNK2 expression using siRNA transfection, protected against apoptosis, as detected by decreased nuclear fragmentation and caspase-3 activity, as well as reduced translocation of Bax to mitochondria. Moreover, release of cathepsin B and D from lysosomes to the cytosol was reduced when JNK expression was suppressed by siRNA, demonstrating a JNK dependent regulation of lysosomal membrane permeabilization. In unirradiated control melanocytes, coimmunoprecipitation showed that Bim was sequestered by Mcl-1, which had a pro-survival function. After UVB irradiation, a significant decrease in Mcl-1 protein level was found, which was prevented by addition of a proteasome inhibitor. The interaction between Bim and Mcl-1 was reduced in response to UVB irradiation and Bim was phosphorylated in a JNK dependent manner. In conclusion, these findings Suggest JNK to have an important pro-apoptotic function following UVB irradiation in human melanocytes, by acting upstream of lysosomal membrane permeabilization and Bim phosphorylation.

In this study, functional polymorphisms of NF-κB1 and NF-κBIα genes were examined in 185 melanoma patients and 438 tumor-free individuals. Associations of the polymorphisms with melanoma risk, age and pigment phenotypes of the patients and clinico-pathological tumor characteristics were analyzed. DNAs were isolated from mononuclear cells of venous blood. Polymorphisms of the genes were genotyped by a PCR-RFLP technique, and transcription level of NF-κBIα was examined by a quantitative real-time reverse transcription PCR. Results showed that both ATTG insertion polymorphism of NF-κB1 and A to G polymorphism of NF-κBIα genes were correlated with melanoma risk, especially, in a combination of ATTG2/ATTGT2 and GG. NF-κB1 ATTG2/ATTG2 and NF-κBIα GG genotypes were associated with male gender and age > 65 years (at diagnosis). Patients with ATTG1/ATTG1 genotype had thinner tumors and lower Clark levels at diagnosis. Frequency of ATTG1/ATTG1 genotype was higher in patients with melanomas on intermittently sun-exposed pattern of the body and NF-κBIα GG was more frequent in the patients with melanomas at rarely exposed sites. There were no differences in the gene transcription level between patients with different NF-κBIα genotypes. These data suggest that NF-κB1 and NF-κBIα genes might be susceptible genes for melanoma risk and functional polymorphisms of these genes might be biological predictors for melanoma progression.

Cutaneous melanoma is characterized by poor patient outcome in its later stages. The search for genetic markers is therefore crucial for the identification of populations at risk for melanoma. Highly polymorphic CA repeats in 3 proximity in the MANBA gene were examined by PCR-capillary electrophoresis in 185 Swedish melanoma patients and 441 tumor-free age- and gender-matched individuals. The associations of the polymorphisms with melanoma risk, the pigment phenotypes of the patients and tumor characteristics were analyzed. A significant difference in allelic distribution between melanoma patients and tumor-free individuals was observed. The frequency of the MANBA genotype <21CAs/>= 21CAs was significantly higher in melanoma patients than in the controls. When comparing allele distribution in patients and their matched controls, the allele <21 CAs was found to be associated with the female gender (39.8 vs. 31.2%, P=0.041, OR=1.46, 95% Cl 1.02-2.10), but not with male gender (34.4 vs. 30.9%, P=0.39). Within the melanoma group, there were no differences in the distribution of the MANBA alleles associated with patient gender or age before or after 55 years at diagnosis, nor was there any association between the MANBA genotype and pigment phenotype or tumor sites. The MANBA allele <21CAs was, however, associated with thin melanomas at diagnosis (Breslow thickness <= 1.5 mm and Clark levels I and II). In conclusion, these data suggest that MANBA polymorphisms might be an indicator of tumor growth and progression and, together with other markers, could be used to identify individuals at increased risk of melanoma.

Aim To clarify the rate of non-attendance (NA) in an out-patient clinic. less thanbrgreater than less thanbrgreater thanMethods Attendance lists of 3592 patients were collected daily from 21 July-21 August and 21 October-21 November, 2009. NA patients were contacted to determine extenuations. To study NA in relation to diagnosis and age, a control group of patients who attended before or after a NA was established. Furthermore, two time periods from 8:00-11:30 AM and 11:30 AM-3:00 PM were compared. less thanbrgreater than less thanbrgreater thanResults In total, 13% NA gave no cancellation (54.2% females and 45.8% males). Divided into age groups, 496 patients 0-25 years old had appointments, but 87 (18.6%) showed NA. In the 26-65 years old, 2188 patients were planned, but 313 (14.1%) showed NA. Over 65 years old, 878 patients were planned, but 69 patients (7.9%) showed NA. NA was higher (P andlt; 0.05) in patients 0-25 years old in comparison with the other age groups. Diagnoses had no influence on the rate of NA (P andgt; 0.05), neither had seasons nor time of the day. The main explanations reported by the NA were: forgetfulness (34.3%), erroneous scheduling (27.7%) and various reasons (38.0%). However, 18.5% had shown NA before while 17.1% were NA first timers. less thanbrgreater than less thanbrgreater thanConclusion The NA rate 13% of 3592 patients was mostly patient-related. Erroneous scheduling was estimated to be 3.6%. NA was more frequent among young patients. NA rate is small in comparison with non-adherence to medicines, however, of major practical and economic consequence for the health system. SMS or e-mail notification and improved scheduling are potential actions to improve NA in the routine.

Background Assessment of hand eczema in a clinical study has been achieved using a scoring system which documents extent of eczema on different areas of the hand. Objectives To investigate whether the same scoring system could be used by patients to communicate current status of hand eczema. Methods In a study of 62 patients (36 women and 26 men, age range 1975 years), the patients own assessment was compared with the assessment by a dermatologist and a dermatological nurse. Standardized information was given to the patient and the form was filled in independently by the patient, the nurse and the dermatologist, during the patients visit to the clinic. Individual area scores were summed to a total score. Results The overall agreement was good, with an interclass correlation (ICC) of 0.61 between patient and dermatologist for the total score. The ICC between nurse and dermatologist was 0.78. Differences between observers were more pronounced for the more severe cases - those with higher numerical scores as assessed by the dermatologist. There was a tendency for women and for patients over the median age of 44 years to set a lower point score than the dermatologist. The concordance of observations from individual anatomical areas was higher for fingertips and nails and lower for the palm and dorsum of the hand. Conclusions Patients are able to report the extent of hand eczema with good accuracy. Self-assessment protocols for hand eczema may well have a place in the monitoring of hand eczema extent over time.

10% of patch-tested patients have a positive reaction to gold. Most lack clinical symptoms, but allergic contact dermatitis (ACD) to gold is increasing. In this study, 77 dermatological outpatients were divided into 3 groups depending on epicutaneous patch test outcomes: a group positive to gold (EPI+), a group negative to gold (EPI-), and a group with irritant reactions to gold (EPI-IR). Lymphocytes were stimulated in vitro with gold sodium thiosulfate. Proliferation was assessed using the lymphocyte transformation test (LTT), and cytokine secretion was assessed using a multibead array (Luminex; Linco Research Inc., St. Charles, MO, USA), in order to evaluate whether an in vitro method with high diagnostic accuracy could be devised. The EPI+ group showed a significantly increased secretion of interferon (IFN)-gamma, interleukin (IL)-2, and IL-13 and also showed a significantly higher stimulation indexes for LTT, compared to the other 2 subject groups. Sensitivity and specificity were calculated for all methods individually and combined, but IFN-gamma assessment alone was the most accurate method for identifying ACD to gold, with sensitivity and specificity of 81.8% and 82.1%, respectively. This method also identified 87.5% of the EPI-IR subjects as non-allergic. Therefore, assessment of secretion of IFN-gamma should be a valuable complement to patch test for diagnosing gold allergy.

Background/aims Skin is a viscoelastic material, comprised of fluidic and fibrous components. Changes in viscoelasticity can arise due to a number of conditions including dehydration, swelling (associated with injury or disease), impaired heart function, rehydration therapy, ageing, scarring, sun exposure and genetic conditions affecting connective tissue. Quantification of changes in skin viscoelasticity due to these processes is of great clinical interest in the fields of therapy monitoring, wound healing and disease screening. However, devices currently available to measure aspects of the mechanical properties of skin have limitations in ease-of-use, accessibility, and depth of measurement. This paper describes a new technique to follow changes in the viscoelasticity of the skin, using a novel approach to an indentation manoeuvre. The device is portable, low-cost and easy to use while at the same time providing rich information on the mechanical response of the skin. Methods The method proposed optically tracks the skins recovery from an initial strain, made with a novel linear indentor, using diffuse side-lighting and a CCD video camera. Upon indentation, the skins elastin fibres are stretched and fluid is displaced from the compressed region. When the indentor is removed, the rate of recovery of the skin from this imprint is therefore principally dependent on its hydration and elasticity. Using the blue colour plane of the image and polarisation filtering, it is possible to examine the surface topography only, and track the decay of the imprint over time. Results The decrease in size of the imprint over time (decay curve) recorded by the device is shown to agree with the theoretical predictions of an appropriate viscoelastic model of skin mechanical behaviour. The contributors to the response measured using the indentation device are fully characterised and evaluated using separate measurement techniques including high-frequency ultrasound, polarisation spectroscopy and optical coherence tomography. Conclusion The device developed is capable of tracking the viscoelastic response of skin to minimal indentation. The high precision achieved using low-cost materials means that the device could be a viable alternative to current technologies.

Patch test positivity to gold is common in western societies, but in contrast to nickel (Ni) allergy it is uncommon that the patch test positive patient shows any clinical symptoms. In this study we investigated cytotoxic effects of gold sodium thiosulphate (GSTS) on peripheral blood mononuclear cells (PBMC), including different T-cell subsets. We also separated lymphocytes from allergic and non-allergic subjects into CD45RA and CD45R0 cell fractions. We also expressed CLA. The fraction of analyzed the effects of GSTS using lymphocyte transformation test, propidium iodide staining and flow cytometry to determine lymphocyte memory status, expression of chemokine receptors and cutaneous lymphocyte-associated antigen (CLA), and compared the results to what has previously been reported on Ni allergy. We found that only the cells from the allergic subjects proliferated in the lymphocyte transformation test (LTT), and in the CD45R0 fraction there was a dose-dependent increase in the fraction of CD3/CD4 cells. Similar to Ni-allergy, these CD3/CD4/CD45R0 cells also expressed CLA. The fraction of CD3/CD8 in the CD45R0 enriched fraction decreased with GSTS exposure. In contrast to Ni allergy, however, we found no differences between the allergic and non-allergic subjects regarding the chemokine receptors CCR4, CXCR3 and CCR10.

Minimally invasive biosensors are of great interest for rapid detection of disease biomarkers for diagnostic screening at the point-of-care. Here we introduce a device which extracts disease-specific biomarkers directly from the upper dermis, without the needle and syringe or resource-intensive blood processing. Using antigen-specific antibodies raised in mice as a model system, we confirm the analytical specificity and sensitivity of the antibody capture and extraction in comparison to the conventional methods based on needle/syringe blood draw followed by processing and antigen-specific ELISAs.

BackgroundMalignant melanoma and non-melanoma skin cancers are among the fastest increasing malignancies in many countries. With the help of new tools, such as teledermoscopy referrals between primary health care and dermatology clinics, the management of these patients could be made more efficient. ObjectiveTo evaluate the diagnostic agreement and interobserver concordance achieved when assessing referrals sent through a mobile teledermoscopic referral system as compared to referrals sent via the current paper-based system without images. MethodsThe referral information from 80 teledermoscopy referrals and 77 paper referrals were evaluated by six Swedish dermatologists. They were asked to answer questions about the probable diagnosis, the priority, and a management decision. ResultsTeledermoscopy generally resulted in higher diagnostic agreement, better triaging and more malignant tumours being booked directly to surgery. The largest difference between the referral methods was seen for invasive melanomas. Referrals for benign lesions were significantly more often correctly resent to primary health care with teledermoscopy. However, referrals for cases of melanoma in situ were also incorrectly resent five times. The interobserver concordance was moderate with both methods. ConclusionBy adding clinical and dermoscopic images to referrals, the triage process for both benign and dangerous skin tumours can be improved. With teledermoscopy, patients with melanoma especially can receive treatment more swiftly.

[No abstract available]

Challenges of treatment for urethritis and cervicitis

Urethritis in men caused by gonorrhoea is symptomatic. Non-gonorrhoic-urethritis (NGU) i.e. caused by Chlamydia trachomatis, Mycoplasma genitalium and occasionally other bacteria is in most cases an asymptomatic infection. Swartz’ definition of microscopic urethritis > 4 polymorphonucleated leucocytes (PML) per high power field (HPF) in > 4 HPF is the general accepted, but has limitations and is dependant on the sampling, microscope, the physician and the patient as well. Cervicitis is even more cumbersome since it is even more often asymptomatic. Other factors such as which contraception method is used, concurrent infections (bacterial vaginosis, candidosis), the microscope and the physician, may have a great impact. Brunham proposed as definition observed mucopurulent discharge from the cervix orifice combined with > 10 PML per HPF in stained endocervical smear. Lindner proposed sign of friability of the portio cervicis. Weström found a correlation of more PML than vaginal epithelial cells in wet mount. The variety of definitions causes problem in comparing scientific studies and at the clinic as well. The intention to treat also means testing and treatment of a current sexual partner as well.

The ever emerging decreased susceptibility of various antibiotics especially against Neisseria gonorrhoeae and M. genitalium makes it even more important to choose whether to treat immediately without having positive tests or to miss a treatment of a potential serious infection. N. gonorrhoeae is visible microscopically in urethral stains from men, but can be missed in smears from endocervix and urethra in women. Cefixim 400 mg stat is the recommended first line antibiotic treatment. Ceftriaxone 500 mg is under consideration to become the first treatment of choice due to emerging decreased susceptibility. M.genitalium will be discussed in another speech by Jørgen Skov Jensen. There are some few reports of antibiotic resistance of Chlamydia trachomatis but this infection is generally still eradicated by tetracycline and macrolide treatment. In an NGU and or unspecific cervicitis doxycycline 100 mg bid for one week is the first treatment of choice. Azithromycin 1 g stat should be used with precaution. If there are persisting signs and or symptoms after doxycycline treatment, azithromycin 500 mg day 1 and 250 mg following four days should be prescribed. Bacterial vaginosis may give symptoms and signs of cervicitis and is also a very common concurrent infection in women with C. trachomatis and M.genitalium as well and treatment with metronidazole or clindamycin should be considered. The fast ways of communication via the Internet and the easy accessible and legal way of an individual to buy antibiotics just for safe or to avoid attending a clinic is a big threat now and even more in the future because of the potential rapid increasing antibiotic resistance of many bacterial infections including STIs

The aim of this thesis was to elucidate urethritis and cervicitis and the possible causes with special reference to Chlamydia trachomatis and Mycoplasma genitalium. Despite mandatory partner notification legislated in 1988, the incidence of C trachomatis infection in Sweden has undergone a 10% annual increase since 1997, following a decline in the early 1990s. Nonchlamydial-non-gonococcal urethritis (and cervicitis) (NCNGU) is more common than chlamydial infection and gonorrhoea at Sexually transmitted disease (SID) clinics. Mycoplasma genitalium, originally isolated in 1980, is one probably important cause of NCNGU.

Specimens from men and women infected with C trachomatis who attended the Örebro STD-clinic (1999-2000) were genotyped by sequencing of the omp 1, which encodes the major outer membrane protein (MOMP) (I, II). Both invasive and first void urine (FVU) specimens (n=237) were successfully sequenced from 231 C trachomatis-positive individuals (96 women and 135 men). Genotype E was the most common strain (47%) followed by F (17%) and K (9%). The prevalence of Ba, D, D/B-120, D/B-185, G, H, Ia and J genotypes was 0.4 to 6%. There were few gap mutations compared with reference strains. 161 sexual networks comprising 688 individuals were compiled. Specimens were sequenced from at least two patients in 47 of 161 networks. In seven of these 47 networks (15%) there were discrepant genotypes. At the follow-up visit five of 204 individuals (2%) were still C trachomatis-positive. Two harboured a new genotype and thus had contracted a new C trachomatis infection. Partner notification was successful in only 30 of 161 networks (19%), meaning that all elicited partners were tested and transmission of infection ceased. The main reason for non-success was insufficient information for partner identification from the index patients and, if the partner attended another clinic, the results of the C trachomatis test were prohibited by Swedish law from being revealed to the tracer.

Microscopic signs, symptoms of infection and prevalence of C trachomatis and M genitalium were compared among men and women attending the Örebro STD-clinic in 2000 (III, IV). In a study performed in 2002, 59 young women invited to the national cervical cancer-screening program were tested for C trachomatis and M genitalium (IV). There was no statistically significant difference in microscopic signs in men or women infected with either of the bacteria. Women infected with C trachomatis or M genitalium more often had microscopic signs of infection than those women in the cancer screening group without infection, and the difference was statistically significant (IV). Symptomatic urethritis was more prevalent in M genitalium than in C trachomatis infected men (III). The prevalence of C trachomatis and M genitalium in male STD-attendees was 12% and 7%, respectively. In female STD-attendees the corresponding figures were 10% and 6%, respectively, whereas only one woman in the screening group was C trachomatis-positive and none was infected with M genitalium (IV). Both C trachomatis and M genitalium were found significantly more often in partners of men and partners of women with the corresponding infection, than in partners of men with a non specific urethritis (NSU) or women with a non-specific urethritis/cervicitis. These studies show that M genitalium is a common infection among STD-clinic attendees and that it is not a widespread commensal bacterium in society.

In an open treatment pilot study (V) in men and women infected with M genitalium, the standard treatment for urethritis and cervicitis, i.e. tetracycline, was compared with azithromycin 500 mg the first day and 250 mg the following four days. Tetracyclines did not eradicate M genitalium in 71% of the women and in 63% of the men, whereas all who were treated with azithromycin were M genitalium negative at the follow-up visit. Randomised controlled trials (RCT) are needed to study azithromycin in different dosages.

Background: Sun exposure habits and the propensity to undertake sun protection differ between individuals. Not least in primary prevention of skin cancer, aiming at reducing ultraviolet (UV) exposure, knowledge about these factors may be of importance. The aim of the present study was to investigate, in a primary health care (PHC) population, the relationship between sun exposure habits/sun protection behaviour/readiness to increase sun protection and gender, age, educational level and skin UV-sensitivity. Methods: The baseline data from a previously performed RCT on skin cancer prevention was used. 415 patients, aged andgt;18 years, visiting a PHC centre in southern Sweden, filled-out a questionnaire mapping sun exposure, readiness to increase sun protection according to the Transtheoretical Model of Behaviour Change (TTM), and the above mentioned factors. Results: Female gender was associated with more frequent suntanning (p andlt; 0.001) and sunbed use (p andlt; 0.05), but also with more extensive sunscreen use (p andlt; 0.001). High age was in general associated with low level of sun exposure and high level of protection. Subjects with low educational level reported less frequent sunscreen use than those with higher educational level, and also chose lower SPF (p andlt; 0.001). For almost all parameters, high skin UV-sensitivity was associated with markedly lower sun exposure (p andlt; 0.001) and more pronounced readiness to increase sun protection. Females and subjects with high educational level reported higher readiness to increase sunscreen use than males and subjects with lower educational level (p andlt; 0.001). Conclusions: Gender, age, educational level and skin type appear to be important factors affecting sun exposure habits and sun protection behaviour, which supports the idea of appropriate mapping of these factors in patients in order to individualise sun protection advice according to the individual patient situation and capabilities.

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.

Background: Few attempts to present a comprehensive scoring instrument for sun exposure and protection have been made. The present paper aims to describe a possible set of questions suitable for such an instrument, comprising the most important aspects of sun exposure and protection. Methods: The material from a previously performed intervention study, using a questionnaire based on Likert scales and on the Transtheoretical Model of Behaviour Change (TTM), was utilised. 213 primary healthcare patients filled in the questionnaire and were randomised into two groups receiving sun protection advice, in Group 1 in letter-form, and in Group 2 orally during a doctor's consultation. In the original study, increased sun protection/readiness to increase sun protection was demonstrated for several items in Group 2, at six months. To compose a comprehensive scoring instrument, five questions concerning sun exposure/protection (intentional tanning, sunscreen use, choice of SPF, number of occasions with sunburn, and time spent in the sun at midday), were selected to give a 20 point behavioural score. Similarly, four TTM-based questions (giving up sunbathing, using clothes for sun protection, using sunscreens, and staying in the shade) gave a 16 point "propensity-to-change"-score. Results: At follow-up, increased sun protection reflected in the behavioural score occurred only in Group 2 (p<0.001). For the propensity-to-change-score, increased readiness to increase sun protection occurred in both groups, but the change was significantly higher in Group 2 (p<0.05). Categorisation of the 20 point behavioural score, into three risk levels, revealed a significantly higher shift of subjects moving to a lower risk level in Group 2 compared to Group 1 (p<0.05). Conclusions: In conclusion, twinning of a summarised Likert scale behavioural score with a TTM-based propensity-to-change-score seems promising for the creation of a questionnaire-based, comprehensive scoring instrument for sun exposure and protection.

Background/objective: The high skin cancer incidence in western society, and its known association with sun exposure habits, makes the area an important target for prevention. We investigated, in a primary healthcare setting, differentiated levels of prevention efforts directed at the propensity of the patient to change his/her sun habits, sun protection behaviour, and attitudes, after information intervention. Additionally, the impact of the performance of a phototest to determine individual sun sensitivity was evaluated. Methods: 308 patients visiting a primary healthcare centre in southern Sweden completed a questionnaire concerning sun habits, sun protection behaviour, and attitudes, and were randomized into one of three groups, representing increasing levels of prevention effort in terms of resources. Feedback on their questionnaire and general preventive sun protection advice was given, in the first group by means of a letter, and in the second and third groups by a doctor's consultation. Group 3 also underwent a phototest, with a self-reading assessment and a written follow-up of the phototest result. Change of sun habits, behaviour, and attitudes, based on the Transtheoretical Model of Behaviour Change and on Likert scale scorings, was evaluated after 6 months, by a repeated questionnaire. Results: Prevention mediated by a doctor's consultation had a clearly better impact on the subjects. The addition of a phototest did not further reinforce this effect in the group as a whole, but it did for a subgroup of individuals with high ultraviolet (UV) sensitivity, as determined by the phototest itself, suggesting that this might actually be a tool to improve outcome in this high-risk group. Conclusion: A personal doctor's consultation is a valuable tool in the effective delivery of preventive information in the general practice setting. In individuals with high UV-sensitivity and thus high risk for skin cancer the performance of a photo-test reinforces a positive outcome in habits, behaviour and attitudes.

In the investigation and management of skin disease, various testing protocols are of importance. The extent to which clinical judgments and decisions on therapy are supported by the performance of such testing can be affected negatively by the lack of time and resources for the performance of tests. In the present study, the possibility of utilizing self-reporting by subjects is investigated. Determination of irritation threshold for sodium lauryl sulphate (SLS) and minimal erythema dose for ultraviolet B were chosen as suitable self-reading protocols. Test reading by 26 subjects instructed in "present" or "absent" reporting of test reactions were compared to trained observer reading. Absolute agreement was found in 76.9 percent of the SLS reactions and in 85 percent of the UVB reactions. Weighted Kappa for the agreement between observations showed values of 0.76 for the SLS reactions and 0.83 for UVB reactions. We conclude that use of the protocols here studied, and other test protocols modified to accommodate a binomial assessment outcome ("+" or "-"), could well lead to an increase in the performance of skin testing. This could be a qualitative advantage for diagnosis and management of skin diseases. Additionally, population studies and even prevention initiatives could be facilitated. © 2010 Dermatology Online Journal.

Background: In both clinical and experimental phototesting, naked eye assessment of erythema has been the main assessment parameter. As with all subjective assessment, variability in recorded results due to variable circumstances around the performance and reading of tests influences reliability and utility of data whether they be interpreted for an individual patient or for a group of research subjects.

Methods: In the present study, variability in the reporting of diameter of ultraviolet B (UVB) erythema has been studied. The erythematous reactions were assessed by the naked eye and with the help of a millimetre-graded ruler by a group of dermatologists and dermatological trainees. Reaction size, objectively quantified by means of laser Doppler perfusion imaging (LDPI) using thresholding of the reaction perfusion, and known size of UVB provocation were used as yardsticks in order to quantify this variability.

Results: Agreement between observers, against known size, was excellent for reactions with a sharp border, but for reactions with a diffuse or indistinct border there was a substantial inter-observer variability. This was also true for the comparison between naked-eye reading and LDPI assessment of the reaction size.

Conclusion: It is concluded that if naked-eye readings are to be the outcome measurement, then provocations/protocols producing distinct borders are an advantage. If borders between provoked and unprovoked skin can be expected to be diffuse, i.e. part of a continuum of response, the use of objective, bioengineering techniques such as LDPI is required. Quantitative methods are also the basis for more detailed presentation and interpretation of test results including information on dose response above the minimal erythema dose.

Background. Inflammation plays an important part in the healing process. Little is known about the extent local inflammatory trauma response interacts with the central circulation and inflammation produced by central organs. The aim of the present study was to examine whether high cut-off microdialysis catheters offer potential to in real time assess interstitial cytokines variations in conjunction to markers of metabolism distal to a blunt vascular contusion. Methods. In a standardised contusion trauma model, microdialysis catheters (high MW (100kDa)) were inserted in the gracilis muscle distal to the trauma for the local assessment of IL-6, IL-8, TNF-a, total protein and the metabolic mediators (glycerol, puruvate and lactate). The contra lateral uninjured leg served as control of the centrally mediated inflammation propagated to the extremities. Results. The trauma led to a significant and quantitatively large (8-10 fold) increase in inflammatory cytokines (IL6 and 8) as measured both in the injured and control legs. There was only a minor, and not significant increase in concentrations of cytokines in the injured leg compared to the control leg.. There were no signs of ischemia in either leg. Conclusion. The new finding in this study is that both central, and local, inflammatory responses as well as metabolic mediators may be assessed continuously in skeletal muscle tissue distal to a major injury in an animal model. The findings suggest that the large trauma elicits a generalised inflammatory response to trauma rather than propagating a local one distal to the trauma.

Background: Refugees needing long-term health care must adapt to new healthcare systems. The aim of this study was to examine the viewpoints of nine refugees in a county in Sweden, with a known chronic disease or functional impairment requiring long-term medical care, on their contacts with care providers regarding treatment and personal needs. Methods: Semi-structured interviews with nine individuals and/or their next of kin. Inductive content analysis was used to identify experiences. Results: "Care organisations/resources" and "professional competence" were the categories extracted. Participants felt cared for due to accessibility to and regular appointments with the same care provider. Visiting different clinics contributed to a negative experience and lack of trust. The staffs interest in participants lives and health contributed to a sense of professionalism. Most participants said the problems experienced were not related to their backgrounds as refugees. Many patients did not fully understand which clinic they were attending or the purpose of the care that the specific clinic provided. Some lacked knowledge of their disease. Conclusions: Health care was perceived as equal to other Swedish citizens and problems experienced were not explained by refugee backgrounds. Lack of information from care providers and being sent to various levels of care created feelings of a lack of overall medical responsibility.

Skin tags (acrochordons) are exceedingly common benign skin lesions. A novel medical device in the form of a flat adhesive patch applies pressure to the base of a skin tag, leading to its removal within 3-6 days. The device was used in a clinical trial to treat and remove skin tags of the neck, upper torso, and axillae in volunteers. In this study, a total of 177 skin tags were treated in 32 individuals. One hundred seventy-two lesions fulfilled intention to treat (ITT) criteria. A majority of ITT lesions (90%) reached final assessment. Successful outcome was highest (90%) for lesions up to 1 mm in base. For lesions up to 2 mm, the rate of successful outcome was 76 percent. The desired outcome was seen in 65 percent of all ITT lesions. The cosmetic outcome after removal was excellent. Discomfort was assessed as minimal during all stages of the procedure. Analysis of data on blood flow in the skin tags during the treatment showed that the outcome was influenced by whether a decrease in blood flow was achieved immediately after application and at 2-3 days, but that the degree of occlusion was not critical. The results of this study illustrate that the device presents a new option for the management of unmet needs in the treatment of skin tags.

Aim: The relationships between microsatellite instability (MSI) and survival in colorectal cancer patients are not consistent. The favorable survival of patient with MSI has been suggested to be related to pronounced inflammatory infiltration; however, the reason for non-association of MSI with survival is unclear. Our aims were to investigate the associations of inflammatory infiltration and tumor necrosis (TN) with microsatellite status and clinicopathological factors in colorectal cancer patients in whom MSI was not related to survival.

Methods: Three hundred and one colorectal adenocar-cinomas were evaluated for inflammatory infiltration and 300 for TN under light microscope.

Results: Low infiltration at invasive margin (c² = 3.94, P = 0.047) and in whole tumor stroma (c² = 3.89, P = 0.049) was associated with MSI, but TN was not (c² = 0.10, P = 0.75). Low infiltration was related to advanced stage (c² = 8.67, P = 0.03), poorer differentiation (c² = 8.84, P = 0.03), DNA non-diploid (c² = 10.04, P = 0.002), higher S-phase fraction (c² = 11.30, P = 0.004), positive p53 expression (c² = 7.94, P = 0.01), and worse survival (P = 0.03 for both univariate and multivariate analyses). Abundant TN was related to advanced stage (c² = 17.74, P = 0.001) and worse survival (P = 0.02 for univariate, and P = 0.05 for multivariate analysis).

Conclusion: The result that high inflammatory infiltration was not related to MSI might help explain the non-association of MSI with survival in colorectal cancer patients.

RAD50 protein is essential for DNA double-strand break repair and maintaining genomic integrity. In this study, we investigated the clinicopathological significance of hRAD50 expression and mutation in microsatellite stable (MSS) and unstable (MSI) colorectal cancers (CRCs). hRAD50 expression was examined in primary CRC (n=268), the corresponding distant (n=69) and adjacent normal mucosa (n=138), and lymph node metastasis (n=44) by immunohistochemistry. hRAD50 mutation was analyzed in 87 primary CRCs by PCR-SSCP-DNA sequencing. hRAD50 expression was increased in MSS primary CRCs, but not MSI ones, compared with distant/adjacent normal mucosa (p<0.05). There was no difference in the hRAD50 expression between primary and metastatic CRCs. The increased hRAD50 expression in MSS primary CRCs was related (p<0.05) or tended to be related (p=0.05) to early tumor stage, better differentiation, high inflammatory infiltration, p53 overexpression. Frameshift mutations of (A)_{9} at coding region of hRAD50 were only found in MSI CRCs. Our results suggest that hRAD50 may play different roles in the development of MSS and MSI CRCs: increased hRAD50 expression in MSS CRCs {may be a cellular response against tumor from further progression}, while hRAD50 mutation may be involved in the development of MSI CRCs.

An in-depth look at cutting-edge research on the body's innate immune system

Innate immunity is the body's first line of protection against potential microbial, viral, and environmental attacks, and the skin and oral mucosa are two of the most powerful barriers that which we rely on to stay well. The definitive book on the subject, Innate Immune System of Skin and Oral Mucosa: Properties and Impact in Pharmaceutics, Cosmetics, and Personal Care Products provides a comprehensive overview of these systems, including coverage of antimicrobial peptides and lipids and microbial challenges and stressors that can influence innate immunity.

Designed to help experts and newcomers alike in fields like dermatology, oral pathology, cosmetics, personal care, and pharmaceuticals, the book is filled with suggestions to assist research and development. Looking at the many challenges facing the innate immune system, including the impact of topically applied skin products and medications, Innate Immune System of Skin and Oral Mucosa paves the way for next generation treatment avenues, preventative approaches, and drug development.

Purpose To evaluate a program initiated in 1987 by the Swedish Melanoma Study Group aiming to provide preventive surveillance to kindreds with hereditary cutaneous melanoma and dysplastic nevus syndrome. Patients and Methods Overall, 2,080 individuals belonging to 280 melanoma families were followed for 14 years between 1987 and 2001 at 12 participating centers. Data were registered in a central database. Results Among 1,912 skin lesions excised during follow-up, 41 melanomas were removed in 32 individuals. Of these, 15 (37%) were in situ melanomas and 26 (63%) invasive melanomas. The median tumor thickness of invasive melanomas was 0.5 mm. Ulceration was absent in 24 of 26 invasive melanomas (92%) and 12 (46%) lacked vertical growth phase. Compared with melanomas in the general Swedish population, the melanomas identified in these kindreds during follow-up had better prognostic characteristics. All melanomas except one were diagnosed in families with two or more first-degree relatives with melanoma. Diagnosis of melanoma occurred in three of eight kindreds with germline CDKN2A mutations, supporting that families with such mutations are at increased risk for melanoma development. Of the 32 individuals who developed melanoma during follow-up, 21 (66%) had had at least one previously diagnosed melanoma. Conclusion This study shows that a coordinated program aimed at detecting and offering skin surveillance in kindreds with hereditary cutaneous melanoma results in a low incidence of melanomas during the follow-up period and that the tumors that do arise have favorable prognostic characteristics.

Dermal exposure to chemicals in cosmetics and hygiene products (e.g. moisturising creams, soaps, shampoos) is increasingly recognized as an important area for risk assessment and regulation. The contents of such products is regulated by classification of exposure types (e.g. stay on/wash off) and regulatory concepts based on toxicological studies and manufacturing or market experience. Positive lists, negative lists or establishment of recommendations on concentration and exposure form a basis for consumer safety. Common problem areas are perfumes, preservatives and the formation of oxidation products after manufacture.

A new patented system, suitable for packages from 100 ml to 5 l, with collapsible plastic bags and unique dosage valves prevents bacteria and air from entering the packaging. Thus the use of preservatives can be avoided.

This may lead to a reduced risk of individual reactions to specific preservatives as well as cross-allergy reactions. The consumer no longer needs to hunt for strange names on small ingredient labels. Also, it could prevent the prospective development of allergy. The avoidance of oxidation products is another advantage.

Introduction The colour of tissue is often of clinicaluse in the diagnosis of tissue homeostasis andphysiological responses to various stimuli.Determining tissue colour changes and borders,however, often poses an intricate problem and visualexamination, constituting clinical praxis, does notallow them to be objectively characterized orquantified. Demands for increased inter- and intraobserverreproducibility have been incentives for theintroduction of objective methods and techniques fortissue colour (e.g. erythema) evaluation. The aim ofthe present paper was to study the border zone of anUVB provoked erythematous response of humanskin in terms of blood volume and oxygenationmeasured by means of diffuse reflectancespectroscopy using a commercial probe.

Material and Methods A provocation model, basedon partial masking of irradiated skin areas, definestwo erythema edges at every skin site responding tothe UV irradiation. In every subject, 5 test sites wereexposed with a constant UV light irradiance (14mW/cm2), but with different exposures times (0, 3,6, 9, 12 seconds). An analysis of the spectral datameasured across the two edges was performed for every scan line. The oxygenized and deoxygenizedhemoglobin contents were estimated in everymeasurement point, using a modified Beer-Lambertmodel.

Results The fit of the experimental data to the model derived by the modified Beer-Lambert law was excellent (R2>0.95). Analyzing data for the chromophore content showed that the erythematous response in provoked areas is dominated by the increase in oxyhemoglobin. The width for the left and right border zone was estimated to 1.81±0.93 mm and 1.90±0.88 mm respectively (M±SD). The unprovoked area between the two edges was estimated to 0.77±0.68 mm.

Conclusion While the chosen data analysis performed satisfactory, the ability of the probe design to differentiate spatial aspects of a reaction with abrupt borders was found to be suboptimal resulting in a probable overestimation of the erythematous edge slope. Probe modification or imaging are possible solutions.

Background/aims: The International Contact Dermatitis Research Group (ICDRG) system for clinical scoring of allergic patch test reactions is well established in clinical dermatology for detailed scoring of allergic reactions. The degree of redness and the presence of swelling, papules, vesicles and bullae are assessed based on visual examination and palpation of reactions. In photographic assessment used in research and tele-dermatology, the scoring is solely based on visual examination of photos. The aim of the study was to evaluate inter-expert variation in patch test reading using photographic images, with ICDRG reading as a reference. Material and methods: Five experienced senior dermatologists each scored 55 positive patch test reactions from 16 slides in an office environment. The slides showed pictures of patch tests with different allergens. The scoring system by ICDRG with six categories for scoring was used. Results: The five dermatologists performed the scoring very differently. When the scoring system was simplified to a tripartite scoring system, the scoring was performed almost similarly by the five clinicians. Conclusion: Based on the present results, it is proposed that the number of scoring categories should be minimized and simplified into negative (including doubtful) reactions, positive reactions and irritant reactions. Such simplified tripartite reading is proposed for research purposes and for tele-dermatology, when scoring is based on photographic images. © Blackwell Munksgaard 2007.

Background: Patients with burns are susceptible to organ failure, and there is indirect evidence that leukocytes may contribute to this process. They may change the expression of cell-surface receptors after certain stimuli, for example, the burn. We therefore aimed to assess the changes induced by the burn in the expression of leukocyte cell-surface receptors CD11b, CD14, CD16, and CD62L on the surface of PMNs and monocytes. We also wanted to examine the dynamics of this activation during the first week after the burn, and to relate it to the size of the injury. Methods: Ten patients with burns of andgt;15% (TBSA) were included in the study. Blood samples were collected on arrival and every consecutive morning during the first week. Healthy volunteers acted as controls. Results: PMN CD11b expression was increased. The extent of PMN CD11b expression correlated negatively to the size of the full thickness burn. Monocyte CD14 expression increased initially but there was no relation to the size of the burn. PMN CD16 expression decreased initially during the first days and the decrease was related to burn size. CD62L did not vary depending on the burn in either PMN or monocytes during the first week after the burn. Conclusion: This study showed that specific receptors on the surface of leukocytes (PMN CD11b, monocyte CD14 and PMN CD16) are affected by the burn. Expression of PMN CD11b and CD16 are related to burn size. Burn-induced effects on the expression of PMN receptors, such as PMN CD11b and CD16, may contribute to burn-induced infection susceptibility.

Cutaneous malignant melanoma (CMM) is one of the most rapidly increasing cancers in the Swedish population. The aetiology of melanoma is a complex interplay between genetics, host characteristics and environmental factors. The host characteristic with the strongest association with CMM is a phenotype with high numbers of common naevi and with dysplastic naevi. The principal environmental factor is sun exposure.

Melanoma risk assessment (paper I)

In a multi-national study including 986 subjects from Sweden, Denmark, the UK, Germany and the Netherlands, the ability of primary care physicians and nurses to identify individuals at increased melanoma risk was assessed. The atypical mole syndrome (AMS) scoring system for melanoma risk was used. The AMS scoring system consists of a five point check list incorporating total body naevus counts, clinically dysplastic naevi and body distribution of naevi. After brief training, the overall agreement in diagnosis between the trained personnel and experienced dermatologists was 94.5% (kappa value 0.70, p<0.05). The study showed that the scoring system successfully can be taught to personnel in primary care.

The naevus phenotype in a population in northern Sweden (paper II)

The naevus phenotype was investigated in a population living in the inland of northern Sweden with a low melanoma incidence. Two hundred and one participants from the community of Storuman were included. The median naevus count was15 common naevi/individual, and the prevalence of dysplastic naevi was 11%. The median naevus count and prevalence of dysplastic naevi were significantly lower than previously described in populations with higher melanoma incidence and higher ambient ultraviolet exposure in southern Sweden. This geographical variation in naevus phenotype might be explained by differences in levels of sun exposure and in genotype.

Cutaneous malignant melanoma in children and adolescents (papers III–V)

During the years 1973 to 2002, 250 cases of primary CMM in individuals aged 0-19 years were reported to the Swedish Cancer Registry. Histological material was available for review in 87% of the cases registered during the two first decades (1973–1992). The diagnostic accuracy in the reviewed material was 88%.

The melanoma incidence doubled in teenagers between the first decade (1973–1982) and the second (1983–1992). During the third decade (1993–2002) the increasing trend was broken. A decrease in incidence was noted in boys during 1993–1997, and in girls during 1998–2002. In younger children the incidence remained extremely low, only 4 cases in children aged 0–9 years were reported during the studied 30-year period. The trunk was the most common melanoma site in boys, and legs and trunk were the most common sites in girls. Superficial spreading melanoma was the most frequent subtype, followed by nodular melanoma. During the two first decades (1973–1992), the median melanoma thickness decreased from 1.5 to 0.9 mm. The melanoma-specific 5-year survival rate was 93%. The most important prognostic factor was melanoma thickness. The prognosis for thin lesions was excellent, during a median follow up time of 12 years, no tumour less than 0.8 mm was lethal according to the Registry.

The results indicate that CMM in teenagers has many features in common with adult onset melanoma. The tudy also underlines the importance of not neglecting lesions suspected for malignant change in children and adolescents, as early detection and removal is crucial for the prognosis also in this young age group.

One-hundred-and-seventy-seven cases of cutaneous malignant melanoma were reported to the Swedish National Cancer Registry in subjects below the age of 20 during the period 1973-92. One-hundred-and-fifty-four (87%) were re-examined histologically, and the original diagnosis of primary cutaneous malignant melanoma was verified in 88%. The age-specific mean annual incidence rate increased to 0.5/100,000 in 1983-92 from 0.2/100,000 in 1973-82. Cutaneous malignant melanoma remained extremely rare in children below the age of 12, where only two cases were found. In subjects aged 12-19, the incidence doubled to 93 cases in the second 10-year period compared to 41 in the first. In boys, most of the melanomas occurred on the trunk, and, in girls, on the legs. Sixty-three percent of the melanomas were of the superficial spreading type, which also was the most rapidly increasing type of melanoma. These results emphasize the importance of surveillance and intensified preventive measures in protecting children and adolescents from the harmful effects of excessive exposure to the sun