Complete Cytolysis and Neonatal Lethality in Keratin 5 Knockout Mice Reveal Its Fundamental Role in Skin Integrity and in Epidermolysis Bullosa Simplex

In human patients, a wide range of mutations in keratin (K) 5 or K14 lead to the blistering skin disorder epidermolysis bullosa simplex. Given that K14 deficiency does not lead to the ablation of a basal cell cytoskeleton because of a compensatory role of K15, we have investigated the requirement for the keratin cytoskeleton in basal cells by inactivating the K5 gene in mice. We report that the K5−/− mice die shortly after birth, lack keratin filaments in the basal epidermis, and are more severely affected than K14−/− mice. In contrast to the K14−/− mice, we detected a strong induction of the wound-healing keratin K6 in the suprabasal epidermis of cytolyzed areas of postnatal K5−/− mice. In addition, K5 and K14 mice differed with respect to tongue lesions. Moreover, we show that in the absence of K5 and other type II keratins, residual K14 and K15 aggregated along hemidesmosomes, demonstrating that individual keratins without a partner are stable in vivo. Our data indicate that K5 may be the natural partner of K15 and K17. We suggest that K5 null mutations may be lethal in human epidermolysis bullosa simplex patients.

Merkel-cell carcinoma of the skin

Merkel-cell carcinoma (MCC) is a rare form of skin cancer of neuroendocrine origin that has been described as the most aggressive cutaneous malignancy. The cell of origin is thought to be the Merkel cell or skin-pressure receptor. It has the propensity for dermal-lymphatic invasion, and nodal and haematogenous spread. Factors that have been implicated in its cause include exposure to sunlight and immunosuppression. The tumour has many similarities to small-cell carcinoma of the lung, with intrinsic sensitivity to ionising radiation and chemotherapy, and an aggressive metastatic potential. The best treatment outcomes can be achieved with early diagnosis and the integration of surgery, radiation, and chemotherapy. The treatment challenges for the clinician are often enormous because many of the patients are elderly and because lesions occur in difficult sites such as the head and neck region and the lower leg.

The effect of skin examination surveys on the incidence of basal cell carcinoma in a Queensland community sample: A 10-year longitudinal study

Skin cancers pose a significant public health problem in high-risk populations. We have prospectively monitored basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) incidence in a Queensland community over a 10-y period by recording newly treated lesions, supplemented by skin examination surveys. Age-standardized incidence rates of people with new histologically confirmed BCC were 2787 per 100,000 person-years at risk (pyar) among men and 1567 per 100,000 pyar among women, and corresponding tumor rates were 5821 per 100,000 pyar and 2733 per 100,000 pyar, respectively. Incidence rates for men with new SCC were 944 per 100,000 pyar and for women 675 per 100,000 pyar; tumor rates were 1754 per 100,000 pyar and 846 per 100,000 pyar, respectively. Incidence rates of BCC tumors but not SCC tumors varied noticeably according to method of surveillance, with BCC incidence rates based on skin examination surveys around three times higher than background treatment rates. This was mostly due to an increase in diagnosis of new BCC on sites other than the head and neck, arms, and hands associated with skin examination surveys and little to do with advancing the time of diagnosis of BCC on these sites as seen by a return to background rates following the examination surveys. We conclude that BCC that might otherwise go unreported are detected during skin examination surveys and thus that such skin cancer screening can influence the apparent burden of skin cancer.

Prevalence of whole-body skin self-examination in a population at high risk for skin cancer (Australia)

Objective: Whole-body skin self-examination (SSE) with presentation of suspicious lesions to a physician may improve early detection of melanoma. The aim of this study was to establish the prevalence and determinants of SSE in a high-risk population in preparation for a community-based randomised controlled trial of screening for melanoma. Methods: A telephone survey reached 3110 residents older than 30 years (overall response rate of 66.9%) randomly selected from 18 regional communities in Queensland, Australia. Results: Overall, 804 (25.9%) participants reported whole-body SSE within the past 12 months and 1055 (33.9%) within the past three years. Whole-body SSE was associated in multivariate logistic regression analysis with younger age (< 50 years); higher education; having received either a whole-body skin examination, recommendation or instruction on SSE by a primary care physician; giving skin checks a high priority; concern about skin cancer and a personal history of skin cancer. Conclusion: Overall, the prevalence of SSE in the present study is among the highest yet observed in Australia, with about one-third of the adult population reporting whole-body SSE in the past three years. People over 50 years, who are at relatively higher risk for skin cancer, currently perform SSE less frequently than younger people.

Effectiveness of topical skin care provided in aged care facilities

Background The 2001 Australian census revealed that adults aged 65 years and over constituted 12.6% of the population, up from 12.1% in 1996. It is projected that this figure will rise to 21% or 5.1 million Australians by 2031. In 1998, 6% (134 000) of adults in Australia aged 65 years and over were residing in nursing homes or hostels and this number is also expected to rise. As skin ages, there is a decreased turnover and replacement of epidermal skin cells, a thinning subcutaneous fat layer and a reduced production of protective oils. These changes can affect the normal functions of the skin such as its role as a barrier to irritants and pathogens, temperature and water regulation. Generally, placement in a long-term care facility indicates an inability of the older person to perform all of the activities of daily living such as skin care. Therefore, skin care management protocols should be available to reduce the likelihood of skin irritation and breakdown and ultimately promote comfort of the older person. Objectives The objective of this review was to determine the best available evidence for the effectiveness and safety of topical skin care regimens for older adults residing in long-term aged care facilities. The primary outcome was the incidence of adverse skin conditions with patient satisfaction considered as a secondary outcome. Search strategy A literature search was performed using the following databases: PubMed (NLM) (1966–4/2003), Embase (1966–4/2003), CINAHL (1966–4/2003), Current Contents (1993–4/2003), Cochrane Library (1966–2/2003), Web of Science (1995–12/2002), Science Citation Index Expanded and ProceedingsFirst (1993–12/2002). Health Technology Assessment websites were also searched. No language restrictions were applied. Selection criteria Systematic reviews of randomised controlled trials, randomised and non-randomised controlled trials evaluating any non-medical intervention or program that aimed to maintain or improve the integrity of skin in older adults were considered for inclusion. Participants were 65 years of age or over and residing in an aged care facility, hospital or long-term care in the community. Studies were excluded if they evaluated pressure-relieving techniques for the prevention of skin breakdown. Data collection and analysis Two independent reviewers assessed study eligibility for inclusion. Study design and quality were tabulated and relative risks, odds ratios, mean differences and associated 95% confidence intervals were calculated from individual comparative studies containing count data. Results The resulting evidence of the effectiveness of topical skin care interventions was variable and dependent upon the skin condition outcome being assessed. The strongest evidence for maintenance of skin condition in incontinent patients found that disposable bodyworn incontinence protection reduced the odds of deterioration of skin condition compared with non-disposable bodyworns. The best evidence for non-pressure relieving topical skin care interventions on pressure sore formation found the no-rinse cleanser Clinisan to be more effective than soap and water at maintaining healthy skin (no ulcers) in elderly incontinent patients in long-term care. The quality of studies examining the effectiveness of topical skin care interventions on the incidence of skin tears was very poor and inconclusive. Topical skin care for prevention of dermatitis found that Sudocrem could reduce the redness of skin compared with zinc cream if applied regularly after each pad change, but not the number of lesions. Topical skin care on dry skin found the Bag Bath/Travel Bath no-rinse skin care cleanser to be more effective at preventing overall skin dryness and most specifically flaking and scaling when compared with the traditional soap and water washing method in residents of a long-term care facility. Information on the safety of topical skin care interventions is lacking. Therefore, because of the lack of evidence, no recommendation on the safety on any intervention included in this review can be made.

Clinical outcomes from skin screening clinics within a community-based melanoma screening program

Background : Within a randomized trial of population screening for melanoma, primary care physicians conducted whole-body skin examinations and referred all patients with suspect lesions to their own doctor for further treatment. Objective: Our aim was to describe characteristics of skin screening participants, clinical screening diagnoses, management following referral, and specificity and yield of screening examinations. Methods: Information collected from consent forms, referral forms, and histopathological reports of lesions that had been excised or undergone biopsy was analyzed by means of descriptive statistics. Results: A total of 16,383 whole-body skin examinations resulted in 2302 referrals (14.1% overall; 15.5% men, 18.2% >= 50 years of age) for 4129 suspect lesions (including 222 suspected melanoma, 1101 suspected basal cell carcinomas [BCCs], 265 suspected squamous cell carcinomas [SCCs]). Histopathologic results were available for 94.8% of 1417 lesions excised and confirmed 33 melanomas (23 in men; 24 in participants ? 50 years of age), 259 BCCs, and 97 SCCs. The probability of detecting skin cancer of any type within the program was 2.4%. The estimated specificity of whole-body skin examinations for melanoma was 86.1% (95% confidence interval = 85.6-86.6). The positive predictive value (number of confirmed/number of lesions excised or biopsied x 100) for melanoma was 2.5%, 19.3% for BCC, and 7.2% for SCC (overall positive predictive value for skin cancer, 28.9%). Limitations: Follow-up of participants with a negative screening examination has not been conducted for the present investigation. Conclusions: The rate of skin cancer detected per 100 patients screened was higher than previously reported and men and attendees older than 50 years more frequently received a referral and diagnosis of melanoma. The specificity for detection of melanoma through whole-body skin examination by a primary care physician was comparable to that of other screening tests, including mammography.

Increase in skin cancer screening during a community-based randomized intervention trial

Survival from cutaneous melanoma is mainly dependent on the thickness of the lesion at diagnosis. Skin screening may increase detection of thin lesions and hence improve survival. Within a community-based randomized controlled trial of a population screening program for melanoma in Queensland, Australia, 9 communities were randomly assigned to the 3-year intervention and 9 communities to the control group. Skin screening prevalence was monitored by cross-sectional surveys at baseline, 1, 2 and 3 years into the intervention and 2 years later. At baseline, prevalence of whole-body clinical skin examination was similar in intervention and control communities. In intervention communities, the prevalence of whole-body skin examinations increased to 29.2%, an absolute difference of 18% from baseline, with a peak of 34.8% 2 years after baseline, and began to decline again at the end of the intervention period. The largest increases were seen in men and women ≥50 years. Uptake of screening did not differ according to melanoma risk factors; however, the decline in screening was less in participants who reported a number of melanoma risk factors. The prevalence of skin self-examination remained stable during the intervention program. No changes were observed in the control communities. These results indicate that the intervention program significantly increased the prevalence of whole-body clinical skin examinations in intervention communities. Once the intervention program ceased, and particularly after skin clinics ceased, levels of skin screening began to decline. The provision of specialized skin screening clinics may be needed to achieve sufficient screening rates should population based screening for skin cancer be considered. © 2005 Wiley-Liss, Inc.

Skin cancer clinics in Australia: workload profile and performance indicators from an analysis of billing data

Objective: To describe the workload profile in a network of Australian skin cancer clinics. Design and setting: Analysis of billing data for the first 6 months of 2005 in a primary-care skin cancer clinic network, consisting of seven clinics and staffed by 20 doctors, located in the Northern Territory, Queensland and New South Wales. Main outcome measures: Consultation to biopsy ratio (CBR); biopsy to treatment ratio (BTR); number of benign naevi excised per melanoma (number needed to treat [NNT]). Results: Of 69780 billed activities, 34 622 (49.6%) were consultations, 19 358 (27.7%) biopsies, 8055 (11.5%) surgical excisions, 2804 (4.0%) additional surgical repairs, 1613 (2.3%) non-surgical treatments of cancers and 3328 (4.8%) treatments of premalignant or non-malignant lesions. A total of 6438 cancers were treated (116 melanomas by excision, 4709 non-melanoma skin cancers [NMSCs] by excision, and 1613 NMSCs non-surgically); 5251 (65.2%) surgical wounds were repaired by direct suture, 2651 (32.9%) by a flap (of which 44.8% were simple flaps), 42 (0.5%) by wedge excision and 111 (1.4%) by grafts. The CBR was 1.79, the BTR was 3.1 and the NNT was 28.6. Conclusions: In this network of Australian skin cancer clinics, one in three biopsies identified a skin cancer (BTR, 3.1), and about 29 benign lesions were excised per melanoma (NNT, 28.6). The estimated NNT was similar to that reported previously in general practice. More data are needed on health outcomes, including effectiveness of treatment and surgical repair.

Computerized Medical Diagnosis of Melanocytic Lesions based on the ABCD approach

Melanoma is a type of skin cancer and is caused by the uncontrolled growth of atypical melanocytes. In recent decades, computer aided diagnosis is used to support medical professionals; however, there is still no globally accepted tool. In this context, similar to state-of-the-art we propose a system that receives a dermatoscopy image and provides a diagnostic if the lesion is benign or malignant. This tool is composed with next modules: Preprocessing, Segmentation, Feature Extraction, and Classification. Preprocessing involves the removal of hairs. Segmentation is to isolate the lesion. Feature extraction is considering the ABCD dermoscopy rule. The classification is performed by the Support Vector Machine. Experimental evidence indicates that the proposal has 90.63 % accuracy, 95 % sensitivity, and 83.33 % specificity on a data-set of 104 dermatoscopy images. These results are favorable considering the performance of diagnosis by traditional progress in the area of dermatology

Study of bacterial agents on external lesions of cultured Sturgeons in Sngar zone of Gilan Province

This study was carried out to isolate and determine bacterial agents in outer lesions of sturgeons in Shahid Dr. Beheshti sturgeon propagation and rearing center in Gilan province. Five species of sturgeons were studied from viewpoint of lesions. A number of 167 specimens of Beluga, 76 specimens of Persian sturgeon, 27 specimens of Russian sturgeon, 42 specimens of stellate and finally 23 specimens of ship had bacterial lesions in different outer parts of their bodies. After sampling and purification, bacterial cultures and biochemical tests were done. After the isolation of bacteria from lesions, Edwardsiella tarda was selected by means of PCR. To obtain molecular acceptance, a pair of E. tarda special primer, forward primer ETa2-351 and reverse primer (Edwsp-780r) were reproduced. A number of 12 E. tarda DNA sample were identified by PCR. After molecular diagnosis, Persian sturgeon challenged with E. tarda for determination of pathogenesis. Challenge method was done by means of injection of different dilutes of E. tarda into dorsal muscle. Sampling of hematopoietic organs (kidney, spleen and liver) were carried out and located in Boin's fixator to perform pathology survey. Also, in order to survey of existence and effect of E. tarda, sampling of kidney for bacterial culture was done by molecular and biochemical methods. Results showed that the most lesions in all five species belonged to abdominal surface. Skin and scutes of this part were involved in comparison with other parts. Also, It was removed some samples from lesions to pathological survey. Microscopic observations showed some levels of destruction of epidermis layers, necrosis of dermis cells and destruction of muscular layer of skin. On the other hand, invasion of inflammatory cells and haemorrhagic in dermis were clear. Based on biochemical results, Aeromonas sobria, A cavia . A. hydrophila , Acinetobacter lowffii , A.baumanni , A.cakoaceticus, Pseudomonas putida , P fluorescens , P.aeruginosa , Serratia marcescens , Escherichia coli , Enterobacter aerogenes , Edwardsiella tarda , Proteus mirabilis , kelebsiella oxytoca and Staphylococcus sp. were isolated from outer lesions. Results of PCR confirmed that E. tarda was before and after challenge in 200 bp range. LD50, 96h was determined 1.2 x 10^5 (CFU/ml). Pathological experiments showed lesions in the kidney, including hemorrhages, degeneration of glumeruli and tubular epithelia, degeneration and necrosis of interestitium tissue, accumulation of protein casts in the tubular lumen. It was observed haemorhages, engorged blood vessels, congestion of sinusoids, increased of melanine, melano macrophage centers, degeneration and necrosis of hepatocytes in the liver. In the spleen, it was recorded congestion, degeneration, necrosis changes in the white and red pulpa, blood engorged and detachment of ellipsoid wall.

Polymerase chain reaction detection of Leishmania DNA in skin biopsy samples in Sri Lanka where the causative agent of cutaneous leishmaniasis is Leishmania donovani

Leishmania donovani is the known causative agent of both cutaneous (CL) and visceral leishmaniasis in Sri Lanka. CL is considered to be under-reported partly due to relatively poor sensitivity and specificity of microscopic diagnosis. We compared robustness of three previously described polymerase chain reaction (PCR) based methods to detect Leishmania DNA in 38 punch biopsy samples from patients presented with suspected lesions in 2010. Both, Leishmania genus-specific JW11/JW12 KDNA and LITSR/L5.8S internal transcribed spacer (ITS)1 PCR assays detected 92% (35/38) of the samples whereas a KDNA assay specific for L. donovani (LdF/LdR) detected only 71% (27/38) of samples. All positive samples showed a L. donovani banding pattern upon HaeIII ITS1 PCR-restriction fragment length polymorphism analysis. PCR assay specificity was evaluated in samples containing Mycobacterium tuberculosis , Mycobacterium leprae , and human DNA, and there was no cross-amplification in JW11/JW12 and LITSR/L5.8S PCR assays. The LdF/LdR PCR assay did not amplify M. leprae or human DNA although 500 bp and 700 bp bands were observed in M. tuberculosis samples. In conclusion, it was successfully shown in this study that it is possible to diagnose Sri Lankan CL with high accuracy, to genus and species identification, using Leishmania DNA PCR assays.