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Skin photoageing results from a combination of factors including ultraviolet (sun) exposure, leading to significant changes in skin morphology and composition. Conventional methods assessing the degree of photoageing, in particular histopathological assessment involve an invasive multistep process. Advances in microscopy have enabled a shift towards non-invasive in vivo microscopy techniques such as reflectance confocal microscopy (RCM) in this context. Computational image analysis of RCM images has the potential to be of use in the non-invasive assessment of photoageing. In this report, we computationally characterized a clinical RCM data set from younger and older Caucasians with varying levels of photoageing. We identified several mathematical relationships that related to the degree of photoageing as assessed by conventional scoring approaches (clinical photography, SCINEXA and RCM). Furthermore, by combining the mathematical features into a single computational assessment score, we observed significant correlations with conventional RCM (P < 0.0001) and the other clinical assessment techniques., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We evaluated the accuracy of diagnoses made from pictures taken with the built-in cameras of mobile phones in a 'real-life' clinical setting. A total of 263 patients took part, who photographed their own lesions where possible, and provided clinical information via a questionnaire. After the teledermatology procedure, each patient was examined face-to-face and a gold standard diagnosis was made. The telemedicine data and pictures were diagnosed by 15 dermatologists. The 299 cases contained 1-22 clinical images each (median 3). Nine dermatologists finished all the cases and the remaining six completed some of them, thus providing 2893 decisions. Overall, 61% of all cases were rated as possible to diagnose and of those, 80% were correct in comparison with the face-to-face diagnosis. Image quality was evaluated and the median was 5 on a 10-point scale. There was a significant correlation between the correct diagnosis and the quality of the photographs taken (P < 0.001). In nearly two-thirds of all cases, a teledermatology diagnosis was possible; however, there was insufficient information to make a telemedicine diagnosis in about one-third of the cases. If applied carefully, mobile phones could be a powerful tool for people to optimize their health care status.

It has been shown that gene mutations which drive the development of malignant melanoma (MM) in humans also lead to emergence of MM when engineered mice. However, little attention has been paid to the clinical and histopathological features of melanocytic lesions and their natural history in a given mouse model. This knowledge is crucial to enable us to understand how engineered mutations influence the initiation and evolution of melanocytic lesions, and/or for the use of mice as a preclinical model to test specific treatments. We recently reported the development of melanocytic proliferations along the spectrum of naevi to MM in a Cdk4 ( R24C/R24C ) ::Tyr- NRAS ( Q ) ( 61K ) mouse model. In this study, we followed the development of lesions over time using digital photography and dermoscopy with the aim to correlate the clinical and histopathological features of lesions developing in this model. We identified two types of lesions. The first are slow-growing dermal MMs that emanate from dermal naevi. The second did not emanate from naevi, grew rapidly, and appeared to be solely confined to the subcutaneous fat. We present a simple staging system for the MMs that progress from naevi, based on depth of extension into the dermis and subcutis. This represents a blueprint for documentation and follow-up of MMs in the live animal, which is critical for the proper use of murine melanoma models., (© 2012 John Wiley & Sons A/S.)

Background: Skin ageing is a complex process due to intrinsic chronological factors (chronoageing) and extrinsic environmental factors. The primary extrinsic factor is cumulative ultraviolet (UV) exposure, and is therefore termed photoageing. The current standards for measuring cumulative sun damage are biopsy histology and skin microtopography. However, skin biopsies are too invasive for population studies and skin replicas render only superficial skin architecture data. Reflectance confocal microscopy (RCM) is a noninvasive imaging tool that allows for in vivo imaging of the skin at quasihistological resolution., Objectives: To define and identify RCM features associated with chronological ageing and photoageing on the forearm in two age groups with different skin phototypes and to assess whether these results agree with previous findings., Methods: We obtained RCM images of dorsal and volar nonlesional skin of the lower forearm of 75 individuals with skin Fitzpatrick phototypes I-III in two age groups (20-30 years and 50-60 years). From each participant and body site, 21 RCM features were assessed and statistically significant differences between the two age groups and different forearm sites determined., Results: RCM enabled identification of changes in architecture, cell morphology and extracellular matrix (collagen) at the level of the epidermis, dermoepidermal junction and papillary dermis. Changes that were correlated with chronological ageing and which were aggravated on the UV-exposed dorsal forearm were: loss of small skin furrows resulting in wider and less intersecting furrows; irregularity of the epidermal honeycomb pattern; irregularly distributed (mottled) pigmented keratinocytes/melanocytes; irregularity of the papillary rings and/or effacement of the rete ridges; and loss of thin collagen fibres and presence of collagen clods., Conclusion: We have tested previously reported and new parameters for skin ageing evaluation by RCM, and identified 15 statistically significant RCM features that can be used to quantify ageing and photoageing in forearm skin noninvasively., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background/objectives: It is well recognized that the number and patterns of acquired melanocytic naevi vary with age, but little is known about naevus patterns in the elderly. This is a cross-sectional study assessing the prevalence, dermoscopic pattern and anatomical distribution of naevus subtypes in a stratified cohort aged between 60 and 89 years., Methods: Fifty-nine patients who attended the Queensland Institute of Dermatology were recruited randomly and evenly distributed into three age groups: 60-69 years; 70-79 years; and 80-89 years. For each participant, total naevus count and morphological naevus types were recorded with respect to age, sex and anatomical location. Flat (Clark's) naevi were further subclassified according to the dermoscopic pattern as reticular, globular or structureless., Results: Using non-parametric methods, naevus counts in the elderly decreased due to the disappearance of reticular naevi (P < 0.05). By contrast, structureless and intradermal (Unna's and Miescher's) naevi seemed to persist even into older age. Naevi on the trunk, limbs, head and neck represented 57.6%, 31.0% and 11.3%, respectively. Notably, no reticular naevi were found on the head and neck area., Conclusions: There is a progressive reduction in total naevus counts with advancing age with respect to a cohort aged greater than 60 years., (© 2011 The Authors; Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.)

Introduction: Dermoscopic understanding of naevus characteristics is essential baseline knowledge for identifying early malignant changes., Method: This cross-sectional study includes 34 patients (56% female, mean age 48 years) at high risk of melanoma (personal or a first degree family member with history of melanoma) and 31 moderate/low melanoma risk volunteers (55% female, mean age 37 years) recruited at the Princess Alexandra Hospital, Brisbane, between October 2009 and March 2010. Participants received full body and individual dermoscopic imaging of clinically significant naevi (≥2 mm on the back of male/female and lower limbs of female and ≥5 mm at other body sites). Dermoscopic patterns of naevi were compared between people at high versus moderate/low melanoma risk according to age and body site., Results: In both high and moderate/low risk groups, globular naevi predominated on the head/neck and abdomen/chest, reticular and non-specific naevi on the back, and non-specific pattern on the upper and lower limbs. Non-specific naevi were the most common in all age groups. In both risk groups, globular naevi were more frequent in the younger age bracket, and reticular naevi were more frequent in the older age bracket. Mixed naevus patterns were infrequent and were more common in the younger age brackets of both risk groups., Conclusion: Our preliminary data shows that dermoscopic naevus patterns were similar for age and body site in people at different levels of melanoma risk, suggesting high melanoma risk does not influence dermoscopic naevus patterns., (© 2011 The Authors; Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.)

Background/objectives: Reflectance confocal microscopy (RCM) can accurately and non-invasively diagnose basal cell carcinoma (BCC). The use of RCM in assessing responses to saucerization or curettage and cautery of BCC has not been established. The aim of the present study was to expound the usefulness of RCM in assessing treatment responses of BCC to saucerization or curettage and cautery 8-12 weeks after treatment., Methods: Eight sequential patients, with 11 superficial BCCs, were recruited. Lesions were evaluated clinically and dermoscopically. Three operators performed RCM imaging for each BCC at baseline and 8-12 weeks after treatment. Diagnostic criteria for RCM diagnosis included streaming of basal cells and the presence of cord-like structures and horizontal vessels. Results were compared against histopathology. Difficulties in establishing tumour clearance were identified and the effectiveness of RCM in assessing the response to treatment was explored., Results: At baseline, all lesions were consistent with superficial BCC. At 8-12 weeks after treatment, RCM correctly diagnosed 10 of 11 lesions as tumour free. Furthermore, RCM was reliable across operators of variable experience and the findings were confirmed histopathologically. Limitations were identified, but appeared to be related to operator experience., Conclusion: The diagnosis of BCC was straightforward and reliable in the present study. Thus, RCM appears useful in assessing the early treatment response of superficial BCC treated with saucerization or curettage and cautery despite operator-dependent limitations., (© 2011 The Authors. Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.)

Skin is a widely used route of delivery for local and systemic drugs and is potentially a route for their delivery as nanoparticles. The skin provides a natural physical barrier against particle penetration, but there are opportunities to deliver therapeutic nanoparticles, especially in diseased skin and to the openings of hair follicles. Whilst nanoparticle drug delivery has been touted as an enabling technology, its potential in treating local skin and systemic diseases has yet to be realised. Most drug delivery particle technologies are based on lipid carriers, i.e. solid lipid nanoparticles and nanoemulsions of around 300 nm in diameter, which are now considered microparticles. Metal nanoparticles are now recognized for seemingly small drug-like characteristics, i.e. antimicrobial activity and skin cancer prevention. We present our unpublished clinical data on nanoparticle penetration and previously published reports that support the hypothesis that nanoparticles >10nm in diameter are unlikely to penetrate through the stratum corneum into viable human skin but will accumulate in the hair follicle openings, especially after massage. However, significant uptake does occur after damage and in certain diseased skin. Current chemistry limits both atom by atom construction of complex particulates and delineating their molecular interactions within biological systems. In this review we discuss the skin as a nanoparticle barrier, recent work in the field of nanoparticle drug delivery to the skin, and future directions currently being explored., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background/objectives: Reflectance confocal microscopy (RCM) is a non-invasive method of imaging human skin in vivo. The purpose of this study was to observe the experience of using RCM on equivocal skin lesions in a tertiary clinical setting in Queensland., Methods: Fifty equivocal lesions on 42 patients were imaged using a reflectance confocal microscope immediately prior to being excised. The images were then analysed blind to the histopathological diagnosis. The experience and problems encountered when using RCM on skin lesions for the first time was also observed., Results: On RCM analysis 12/13 melanomas (92.3% sensitivity, 75% specificity), 19/22 benign naevi (86% sensitivity, 95% specificity), 6/9 basal cell carcinomas (66.7% sensitivity, 100% specificity)and 6/6 squamous cell carcinomas and its precursors (100% sensitivity, 75% specificity) were diagnosed correctly when using histology as the gold standard. We identified three common problems that affected image quality: object artefacts; positioning artefacts; and movement artefacts., Conclusions: Using simple techniques we found that common RCM features were readily identifiable and common artefacts could be minimized, making RCM a useful tool to aid the diagnosis of equivocal skin lesions in a clinical setting., (© 2011 The Authors. Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.)

Early detection of lesions while minimising the unnecessary removal of benign lesions is the clinical aim in melanoma diagnosis. In this context, several non-invasive diagnostic modalities, such as dermoscopy, total body photography, and reflectance confocal microscopy have emerged in recent years aiming at increasing diagnostic accuracy. The main developments in this field are the integration of dermoscopy and digital photography into clinical practice.

Reflectance confocal microscopy (RCM) enables in vivo imaging of human skin at a quasi histologic resolution. The black-and-white RCM images show horizontal sections of the skin, at a maximum depth of 350 microm. To date, the RCM features of a significant number of skin conditions have been described. The main focus of the research community investigating RCM, however, lies on describing and diagnosing melanocytic skin lesions. Taking into account all RCM studies dealing with diagnostic accuracy in melanocytic skin lesions, sensitivity and specificity of approximately 90% and 86% could be found. Improvement of diagnostic accuracy, improved assessment of dermoscopic-histologic correlation, in vivo biopsy side selection, surgical margin assessment, and response control of conservative therapies in skin diseases are some of the major advantages of this novel imaging method. Additionally, RCM holds inherent potential for teledermatologic application and automated image analyzing. This article describes morphologic features of diverse skin lesions and features of "normal skin," summarizes diagnostic advances of RCM, compares studies dealing with diagnostic applicability, and discusses further research goals of this exciting new imaging technique.

Dermatology is perhaps the most visual specialty in medicine, making it ideally suited for modern telemedicine techniques, as has been shown in a number of recent studies investigating feasibility and reliability of teledermatology. It has generally demonstrated high levels of concordance in diagnosis and management plans compared with face-to-face consultations. Teledermatology has been also used for various purposes, including triage, diagnostic and management services, and second opinion services for primary care practitioners. It has been set up in a number of ways: 1) direct referral for primary care using images and clinical history sent to secondary care dermatology services for second opinion and for triage referrals; and 2) facilitating community-based clinics led by nurses or general practitioners. Moreover, in the last years new fields in teledermatology have grown up. Teledermoscopy is a promising area for melanoma screening as well as for diagnosis and management of equivocal pigmented skin lesions. The feasibility of mobile teledermatology and mobile teledermoscopy has been recently proved and these new facilities have the potential to become an easy applicable tool for everyone and may open the door for a new flexible triage system for detection of skin cancer in general and melanoma in particular. The implementation of virtual slide systems for teledermatopathology has allowed avoiding the limitations imposed by conventional photographs. Finally, web consultations in dermatology are a rather new tool that became available in the last years and teledermatologic services through the Internet offer many possibilities, including continuing medical education, on-line atlases and databases, and specific web application suited for teledermatology (i.e. www.telederm.org).

"Telemedicine" is defined as the use of telecommunication technologies for the exchange of medical information across distances. Applications include patient management as well as research and education. Teledermatology is a steadily growing category of telemedicine. This article presents general aspects of telemedicine, such as modes of data transmission, and practical applications with a special emphasis on their significance for teledermatology.

Dermatology is perhaps the most visual specialty in medicine, making it ideally suited for modern telemedicine techniques, as has been shown in a number of recent studies investigating feasibility and reliability of teledermatology. It has generally demonstrated high levels of concordance in diagnosis and management plans compared with face-to-face consultations. Teledermatology also has been used for various purposes, including triage, diagnostic and management services, and second-opinion services for primary care practitioners. It has been set up in a number of ways: (1) direct referral for primary care using images and clinical history sent to secondary care dermatology services for second opinion and for triage referrals and (2) facilitating community-based clinics led by nurses or general practitioners. Moreover, in the last years new fields in teledermatology have grown up. Teledermoscopy is a promising area for melanoma screening as well as for the diagnosis and management of equivocal pigmented skin lesions. The feasibility of mobile teledermatology and mobile teledermoscopy recently has been proven, and these new facilities have the potential to become an easy applicable tool for everyone and may open the door for a new flexible triage system for detection of skin cancer in general and melanoma in particular. The implementation of virtual slide systems for teledermatopathology has allowed avoiding the limitations imposed by conventional microphotography. Finally, web consultations in dermatology are a rather new tool that became available in the last years and teledermatologic services through the Internet offer many possibilities, including continuing medical education, on-line atlases and databases, and specific web application suited for teledermatology (ie, www.telederm.org).

Telemedicine is an emerging field within medicine with potential to revolutionize the delivery of health care. It is defined as the use of telecommunication technologies to transfer medical information. Teledermatology is a category of telemedicine. Early experiments were already made at the beginning of the 20(th) century, the breakthrough happened in the nineties because of the rapid progress of telecommunication technology. The latest advance is mobile telemedicine which is characterized by the use of mobile devices such as mobile phone and PDA (personal digital assistant). Advantages of telemedicine are the possibility of remote patient-care as well as the easy and fast access to expert opinions and education. This can either happen through exchange of previously stored data/images (store-and-forward method) or in real time. Since our society is increasingly becoming interconnected via technical advances, it is essential that medicine also has an objective understanding of the topic.

We investigated the diagnostic agreement between teledermatology based on images from a mobile phone camera and face-to-face (FTF) dermatology. Diagnostic agreement was assessed for two teledermatologists (TD) in comparison with FTF consultations in 58 subjects. In almost three-quarters of the cases (TD1: 71%; TD2: 76%), the telediagnosis was fully concordant with the FTF diagnosis. Furthermore, the diagnosed diseases were almost all in the same diagnostic category (TD1: 97%; TD2: 90%). If mobile teledermatology had been used for remote triage, TD1 could have treated 53% subjects remotely and 47% subjects would have had to consult a dermatologist FTF. TD2 could have treated 59% subjects remotely, whereas 41% subjects would have had to consult a dermatologist FTF. Forty-eight subjects responded to a questionnaire, of whom only 10 had any concerns regarding teledermatology. Thirty-one subjects stated that they would be willing to pay to use a similar service in future and suggested an amount ranging from euro5 to euro50 per consultation (mean euro22) (euro = pound0.7, US $1.4). These results are encouraging as patient acceptance and reimbursement represent potential obstacles to the implementation of telemedicine services.

Hepatitis B virus (HBV) precore mutants are associated often with highly productive infection in hepatitis B surface antigen (HBsAg) carriers lacking hepatitis B e antigen (HBeAg) but positive for anti-HBe, rendering serological identification of infectious individuals unreliable. Although considered initially to be limited mostly to the Mediterranean area, more recent studies suggest a significant presence of these mutants in northern European countries. The sequence of the precore region was determined and examined for mutations from HBV isolates of 99 German chronic HBsAg carriers positive for HBV-DNA and either HBeAg (n = 15) or anti-HBe (n = 84). In addition, clinical data of individuals carrying wild-type virus and those with precore mutants were compared. HBV precore mutants were found in more than half (44/84) of all HBeAg-negative, anti-HBe-positive virus carriers. There was no difference between carriers of wild-type and precore mutant HBV in the level of viremia or in the clinical course of chronic infection. In conclusion, HBV precore mutants are common in Germany and can therefore present a diagnostic problem for serological testing. However, precore mutants do not appear to have a detrimental effect on the course of chronic HBV infection.

Objective: The purpose of this biomechanical in-vitro-study was to compare two different PLIF-techniques with two types of implants on human lumbar spine: PLIF with threaded cages, (Bagby and Kuslich, Spinetech, Minneapolis, USA) and PLIF with the Moss-Miami-implants, (DePuy International Limited, Leeds, Great Britain)., Methods: Six cadaveric human lumbar spine segments L2-5 were explanted, frozen at -20 degrees C and thawed before preparation. They were cut in two parts by discectomie and arthrotomie L3/4, so six specimen L2/3 and six specimen L4/5 were obtained and used in a crossover-trial. Analysis included testing in a tension-torsion-machine under axial compression with 600 N, rotation (left-right) with 25 Nm and shearing forces with 250 N without preload. This was first done in the intact and then in the fused specimen., Results: Stiffness before treatment was comparable in both groups irrespective of location. Posttreatment stiffness was higher with MOSS-MIAMI-implants as compared to PLIF with BAK-cages. Average relative superiority (and 95%-confidence intervall) were 1.98 (1.01-3.69) for compression, 2.30 (0.85-6.24) for rotation and 1.73 (0.78-3.84) for shearing. Statistical comparison of log posttreatment stiffness was significant for compression but not for rotation and shearing (2-sided independent crossover t-test)., Conclusion: This biomechanical in-vitro-study demonstrates the higher initial stability of PLIF with titanium surgical mesh and posterior instrumentation when compared to PLIF with threaded cages alone.

In a prospective pilot study we investigated the percentage of immunocompetent cells in the peripheral blood in 146 patients (lymphocytes, leucocytes, monocytes, T cells, B cells, NK cells, T-helper cells, T-suppressor cells, ratio T-helper/T-suppressor cells, activated T cells HLA-DR) by flow cytometry. The immunologic parameters were derived from patients with oral and oropharyngeal squamous cell carcinomas, precancerous lesions and benign tumours and from a group of heavy smokers and alcoholics. Carcinoma patients (n = 46) were compared with risk groups and a reference group consisting of patients with inflammatory disease. Within the collective of carcinoma patients we measured the immune status before and after chemo-, radio- and operative therapy. We also analysed the immune parameters in relation to clinical and histomorphological parameters (TNM status, grading). The univariate analysis of monocytes showed significant relationships between on the one hand carcinoma patients and on the other alcoholics and those with benign tumours and precancerous lesions. In precancerous lesions NK cells were significantly increased compared with alcoholics and the reference group. A significant decrease in B cells in carcinoma patients may show incipient insufficiency of the humoral immunity. The immune parameters showed a different reaction depending on therapy. After irradiation we found a significant increase of T-suppressor cytotoxic cells and decreases in B and T-helper cells. Chemotherapy showed an increase in T and T-helper cells and a decrease in B cells. Surgical therapy alone yielded an increase in B cells. The comparison of all pre- and posttherapeutic parameters showed significant changes only in activated T cells HLA-DR. We found no correlation between prognostic clinico-pathological factors and immune parameters. No changes were found in a multivariate analysis.