Single-center, noninterventional clinical trial to assess the safety, efficacy, and tolerability of a dimeticone-based medical device in facilitating the removal of scales after topical application in patients with psoriasis corporis or psoriasis capitis.

INTRODUCTION: Psoriasis is a frequent inflammatory skin disease affecting ~2%-3% of the population in western countries. Scaling of the psoriatic lesions is the most impairing symptom in patients with psoriasis. In contrast to conventional keratolytic treatment concepts containing salicylic acid or urea, a dimeticone-based medical device (Loyon®) removes scales in a physical way without any pharmacological effect. OBJECTIVE: To assess the efficacy and tolerability of a dimeticone-based medical device in removal of scales in patients with psoriasis corporis/capitis under real-life conditions. METHODS: Forty patients with psoriasis capitis or corporis were included and received once-daily treatments for 7 days. Clinical assessment of the psoriasis area severity index score (psoriasis corporis) and the psoriasis scalp severity index score (psoriasis capitis) was performed and evaluated at baseline, after 3 and 7 days of treatment. Baseline scaling scores and redness scores were calculated for two target lesions of the scalp or the body on a 5-point scale each. RESULTS: For the primary efficacy variable scaling score, a statistically significant decrease was observed after treatment, with a relative reduction in scaling of 36.8% after 7 days of treatment within patients affected by psoriasis capitis. Treatment success was achieved in 76.8% of patients with psoriasis capitis, and time to treatment success was evaluated to be 4.14 days for these patients and 4.33 days for patients suffering from psoriasis corporis. CONCLUSION: In conclusion, this trial demonstrated that the dimeticone-based medical device is a safe, well-tolerated, practicable, and efficient keratolytic compound, which can be well implemented in and recommended for standard therapy of psoriasis.

Topical, Non-Medicated LOYON(®) in Facilitating the Removal of Scaling in Infants and Children with Cradle Cap: a Proof-of-Concept Pilot Study.

INTRODUCTION: Cradle cap is a very common condition in infants that presents as greasy, scaly patches on the scalp within the first weeks of life. Although usually disappearing by itself, the condition worries parents because of its appearance. When removing the scales, it is crucial to prevent spot bleedings to avoid infections. The investigational medical device LOYON(®) (Cetiol(®) CC, dimethicone) solution (G. Pohl-Boskamp GmbH & Co. KG, Hohenlockstedt, Germany) has the potential to meet these needs since it removes scales gently. It was, therefore, the aim of this proof-of-concept study to assess the efficacy and safety of topically applied, non-medicated LOYON(®) in facilitating the removal of scaling in infants and children with cradle cap without inducing spot bleedings. METHODS: This single-center, open, proof-of-concept, pilot study was conducted in 20 male or female infants/children aged 3-36 months with clinically diagnosed cradle cap. The 8-day study period included one to three applications of LOYON(®). Clinical assessment of scaling and secondary parameters was performed at baseline and after treatment. Adverse events were recorded. A questionnaire on subjective efficacy and usability was handed out to the parents. RESULTS: With a maximum of three applications of LOYON(®) applied to 20 subjects, a reduction in scaling intensity from moderate or severe to very mild or mild was achieved in 80% of the subjects. Treatment success, defined as the reduction of the scaling baseline score by at least two points, was achieved in 50% of subjects. Results of this study do not indicate any safety concern. No spot bleedings were observed. LOYON(®) was generally well tolerated and overall treatment was rated as "good" by the parents/legal guardians. CONCLUSION: This study suggests that LOYON(®) is well tolerated, safe and effective in facilitating the removal of scaling in infants and children with cradle cap. With its gentle approach and rapid effect, LOYON(®) thus represents a good alternative to home remedies for treatment of cradle cap.

Efficacy of chemical and botanical over-the-counter pediculicides available in Brazil, and off-label treatments, against head lice ex vivo.

BACKGROUND: There is a lack of reliable data on the efficacy of over-the-counter (OTC) pediculicides in Brazil. METHODS: We performed ex vivo assays of eight marketed pediculicides: 1% permethrin (Kwell, Clean Hair, Keltrina, Nedax), 0.02% deltamethrin (Deltacid, Pediderm), and two "natural" products (Piolho e Lêndea, Pilogenio). We also tested 5% permethrin (Keltrina Plus), traditional home remedies and an ivermectin-based product used in veterinary medicine. Head lice (49-52 per group) were immersed in the compound for 3 min and washed after 20 min to simulate the typical in vivo treatment protocol. Lice were examined for activity up to 24 h using stringent criteria for survival. RESULTS: Of the permethrin containing products, highest mortality was observed with Kwell and Clean Hair (97.9 and 90.2% after 4 h). Keltrina, Nedax, Keltrina Plus, and the two deltamethrin-based products showed only a low efficacy of <60% after 4 h. With exception of pure coconut oil (80% mortality after 4 h), home remedies showed a very low efficacy, and both marketed products killed few lice. The ivermectin-based product caused a mortality of 100% after 4 h. CONCLUSIONS: Most Brazilian OTC products did not show a satisfactory efficacy against head lice. Resistance may be present. Ivermectin and coconut oil are promising compounds for topical treatment. Laboratory-based tests should be used to assess resistance patterns and to identify formulations of the active ingredient that increase the efficacy. Standardized testing should be performed before a product is licensed for head lice treatment.

Role of erythropoietin receptor expression in malignant melanoma.

Recombinant human erythropoietin (Epo) is used to prevent and treat tumor-related anemia and improve quality of life in cancer patients. Recent evidence suggested that Epo may adversely affect the survival of selected cancer patients by promoting tumor growth, inhibition of apoptosis, and induction of migration. Epo unfolds its effect on the Epo receptor (EpoR). We show--to the best of our knowledge for the first time--significantly increased EpoR expression in clinical melanoma metastases and primary melanomas in comparison with different sets of nevi by quantitative real-time reverse transcriptase-PCR, immunohistochemistry, and western blot analysis. When assessing the functionality of the EpoR-signaling pathway, recombinant human Epo led to the phosphorylation of JAK-2, signal transducers and activators of transcription 3 (STAT3), and ERK1/2 in several of the melanoma cell lines that were analyzed. Besides, Epo counteracted cisplatin-induced cell death in BLM and MV3 cells. Finally, Epo promoted cell migration of MV3 cells, whereas inhibition of the JAK/STAT and ERK1/2 pathways reduced Epo-mediated migration. In summary, we show the overexpression of functional EpoR expression in about half of the analyzed clinical melanoma metastasis specimens and show anti-apoptotic as well as pro-migratory effects of Epo, which is of importance for the treatment of anemia in advanced melanoma.

Bed bugs, leeches and hookworm larvae in the skin.

Bed bugs, leeches, and hookworm-related cutaneous larva migrans are skin infestations that are usually considered of minor importance because they produce discomfort rather than cause or transmit disease. Bed bugs have been increasing tremendously in high-income countries in recent years, causing distress to affected individuals and economic loss. Infestation by land leeches causes mainly unpleasant skin reactions, whereas infestation by aquatic leeches may be more dangerous, leading to anemia and in severe cases, to death. Cutaneous larva migrans produces an intense pruritus that can be exasperating for the patient and cause sleep disturbance. An overview is given of these three infestations with a discussion of the causative agents, transmission, clinical manifestations, diagnosis, and treatment.

Accuracy of diagnosis of pediculosis capitis: visual inspection vs wet combing.

OBJECTIVE: To determine the diagnostic accuracy of visual inspection and wet combing in pediculosis capitis (head lice infestation). Visual inspection of 5 predilection sites (temples, behind the ears, and neck) was performed first, followed by wet combing of hair moistened with conditioner. Presence of mobile stages was defined as active infestation, presence of nits alone as historic infestation. DESIGN: Observer-blinded comparison of 2 diagnostic methods. SETTING: Five primary schools in which head lice infestation was epidemic. PARTICIPANTS: A total of 304 students aged 6 to 12 years. MAIN OUTCOME MEASURES: Presence of nymph, adults, and nits; sensitivity, predictive value, and accuracy of both methods. RESULTS: Visual inspection underestimated the true prevalence of active infestation by a factor of 3.5. The sensitivity of wet combing in diagnosing active infestation was significantly higher than of visual inspection (90.5% vs 28.6%; P < .001). The accuracy of the former method was 99.3% and that of the latter method, 95%. In contrast, visual inspection had a higher sensitivity for the diagnosis of historic infestation (86.1% vs 68.4%; P < .001). CONCLUSIONS: Wet combing is a very accurate method to diagnose active head lice infestation. Visual inspection is the method of choice, if one aims to determine the frequency of carriers of eggs or nits.

The epidemiology of scabies in an impoverished community in rural Brazil: presence and severity of disease are associated with poor living conditions and illiteracy.

BACKGROUND: We sought to study the epidemiology of scabies and to identify risk factors of severe disease in an impoverished rural community in northeast Brazil. METHODS: The study was designed as a repeated cross-sectional study based on two door-to-door surveys. One survey was carried out in the rainy season, the other in the dry season. The inhabitants of the community were examined for the presence of scabies and demographic, socioeconomic, and behavioral risk factors were assessed. Risk factors were analyzed using bivariate and multivariate regression analysis. RESULTS: The overall prevalence was 9.8% with no significant variation between seasons and the incidence was estimated to be 196/1000 person-years. The highest prevalence (18.2%) was observed in children younger than 4 years. Risk factors in the bivariate analysis were young age, presence of many children in the household, illiteracy, low family income, poor housing, sharing clothes and towels, and irregular use of shower. Age younger than 15 years, illiteracy, sharing of clothes, and living in the community for more than 6 months remained significant independent risk factors in multivariate regression analysis. LIMITATIONS: We used a clinical case definition; specificity and sensitivity were not verified. Men were underrepresented in the study population. CONCLUSIONS: In this impoverished community scabies is an important health problem characterized by continuous transmission throughout the year. The parasitic skin disease is embedded in a complex web of causation characterized by poor living conditions and a low level of education.

Transcriptional regulation of ASK/Dbf4 in cutaneous melanoma is dependent on E2F1.

BACKGROUND: Melanoma is a complex genetic disease, the management of which will require an in-depth understanding of the biology underlying its initiation and progression. Recently, we have reported the differential regulation of a novel gene, namely ASK/Dbf4, in melanoma and suggested upregulation of ASK/Dbf4 as a novel molecular determinant with prognostic relevance that confers a proliferative advantage in cutaneous melanoma. As trans-acting factor binding is fundamental to understand the regulation of gene expression, this study focuses on characterization of the specific transcriptional regulation of ASK/Dbf4 in melanoma. OBJECTIVE: We investigated whether ASK/Dbf4 is a transcriptional target of the important cell cycle regulator E2F1 in melanoma. RESULTS: As evidenced by gel supershift assays on nuclear extracts from various melanoma cell lines (SK-MEL-28, MV3, M13, A375 and BLM), E2F1 bound to the ASK/Dbf4 minimal promoter (MP). In addition, cisplatin-mediated abrogation of E2F1 binding to the ASK/Dbf4 MP resulted in a transcriptional decrease in ASK/Dbf4. Further, the current study also demonstrated that ASK/Dbf4 regulation was refractory to UVB, a well-known risk factor for melanoma. CONCLUSIONS: In summary, our study not only elucidated that ASK/Dbf4, a novel cell survival gene in melanoma was transcriptionally regulated by E2F1, but also that the induction of ASK/Dbf4 was refractory to UVB exposure suggesting that its upregulation was not an early event in melanomagenesis.

Cutaneous melanoma: fishing with chips.

DNA microarray technology is a versatile platform that allows rapid genetic analysis to take place on a genome-wide scale and has revolutionized the way cancers are studied. This platform has enabled researchers to characterize mechanisms central to tumorigenesis and understand important molecular events in the multi-step tumor progression model of cutaneous melanoma and other cancers. In melanoma, multiple global gene expression profiling studies using various DNA microarray platforms and various experimental designs have been performed. Each study has been able to capture and characterize either the involvement of a novel pathway or a novel cause-effect-relationship. The use of microarrays to define subclasses, to identify differentially regulated genes within a mutational context to analyze epigenetically regulated genes has resulted in an unprecedented understanding of the biology of cutaneous melanoma that may lead to more accurate diagnosis, more comprehensive prognosis, prediction and more effective therapeutic interventions. Related DNA microarray platforms like array-comparative genomic hybridization (CGH) have also been instrumental to identify many non-random chromosomal alterations; however, studies identifying validated targets as a result of CGH are limited. Thus, there exists significant opportunity to discover novel melanoma genes and translate such discoveries into meaningful clinical endpoints. In this review, we focus on various DNA microarray-based studies performed in cutaneous melanoma and summarize our current understanding of the genetics and biology of melanoma progression derived from accumulating genomic information.

Behavioral conditioning of antihistamine effects in patients with allergic rhinitis.

BACKGROUND: Allergic symptoms can be induced by behavioral conditioning. However, the conditionability of antiallergic effects has not yet been studied. Thus, we investigated whether the effects of a histamine 1 (H(1)) receptor antagonist are inducible in patients suffering from house-dust mite allergy using a behavioral conditioning procedure. METHODS: During the association phase, 30 patients with allergic house-dust mite rhinitis received a novel-tasting drink once daily, followed by a standard dose of the H(1) receptor antagonist, desloratadine, on 5 consecutive days. After 9 days of drug washout, the evocation trial commenced: 10 patients received water together with an identically looking placebo pill (water group), 11 patients were re-exposed to the novel-tasting drink and received a placebo pill [conditioned stimulus (CS); CS group] and 9 patients received water and desloratadine (drug group). RESULTS: During the association phase, desloratadine treatment decreased the subjective total symptom scores, attenuated the effects of the skin prick test for histamine and reduced basophil activation ex vivo in all groups. During the evocation trial, the water group, in which subjects were not re-exposed to the gustatory stimulus, showed a reduction in subjective total symptom scores and skin prick test results, but no inhibition of basophil activation. In contrast, re-exposure to the novel-tasting drink decreased basophil activation, the skin prick test result and the subjective symptom score in the CS group to a degree that was similar to the effects of desloratadine in the drug group. CONCLUSIONS: These data show that behaviorally conditioned effects are not only able to relieve subjective rhinitis symptoms and allergic skin reactions, but also to induce changes in effector immune functions.

Role of viruses in the development of squamous cell cancer and melanoma.

In this chapter, the evidence for the role of human papilloma virus (HPV) in the pathogenesis of squamous cell cancer of the skin will be reviewed. Considerable dispute exists questioning the etiological role of HPV. This is due to the low copy number ofHPV DNA in skin cancers and additional cofactors such as UV exposure, immunosuppression, light skin color and hyperproliferative skin disease as well as the genetic background of the host. These additional cofactors are probably required because of the weak transforming activity of cutaneous HPV types in contrast to high-risk genital HPV strains. On a different note, the involvement of viruses in the etiology of melanoma has only recently been suggested. Melanoma-associated retrovirus (MelARV) has been detected in mice and men and was shown to subvert immunosurveillance besides insertional mutagenesis. The state of the art of viral participation in melanomagenesis will be discussed.

SMaRT technology enables gene expression repair in skin gene therapy.

In this issue, Wally et al. (2008) report successful gene expression repair by spliceosome-mediated RNA trans-splicing (SMaRT), a novel achievement in molecular medicine. In their model, SMaRT was able to replace a mutation of the plectin gene in epidermolysis bullosa simplex with muscular dystrophy. This approach is particularly attractive for skin gene therapy of dominant-negative mutations present in a number of blistering genodermatoses.

Taxol-induced mitochondrial stress in melanoma cells is mediated by activation of c-Jun N-terminal kinase (JNK) and p38 pathways via uncoupling protein 2.

Taxol (paclitaxel) is a new antineoplastic drug that has shown promise in the treatment of different tumor types. However, the molecular mechanisms governing taxol-induced apoptosis are poorly understood. Activation of mitogen-activated protein (MAP) kinases is induced by a wide variety of external stress signals and may lead to apoptosis. Therefore, we challenged the human melanoma cell lines A375 and BLM with taxol and characterized the molecular mechanisms regulating taxol-induced apoptosis. Taxol resulted in the activation of apoptosis signal regulated kinase (ASK)1, c-jun NH(2)-terminal kinase (JNK), p38(MAPK) and extracellular-regulated kinase (ERK) together with the downregulation of uncoupling protein 2 (UCP2). In addition, reactive oxygen species (ROS) were induced and DNA-binding activity of the transcription factors AP-1, ATF-2 and ELK-1 was enhanced. Ultimately, cytochrome c was released, and caspases-9 and -3 as well as PARP were cleaved. Pretreatment of melanoma cells with the JNK inhibitor (SP600125) or the p38 inhibitor (SB203580) blocked taxol-induced UCP2 downregulation, ROS generation and apoptosis, whereas the ERK inhibitor (PD98059) had no such effect. Our data provide evidence that taxol-induced mitochondrial stress occurs through the activation of both JNK and p38 pathways, and suggest a novel role for UCP2 in the modulation of taxol-induced apoptosis of melanoma cells.

Interaction of Adenovirus E1A with the HHV8 Promoter of Latent Genes: E1A Proteins are Able to Activate the HHV-8 LANAp in MV3 Reporter Cells.

Human herpesvirus 8 (HHV-8) is associated with Kaposi's sarcoma, body cavity-based lymphoma, and Castleman's disease. Adenoviral (Ad) E1A proteins regulate the activity of cellular and viral promoters/enhancers and transcription factors and can suppress tumorigenicity of human cancers. As (i) HHV-8 and Ad may co-exist in immunocompromised patients and (ii) E1A might be considered as therapeutic transgene for HHV-8-associated neoplasms we investigated whether the promoter of the latency-associated nuclear antigen (LANAp) controlling expression of vCyclin, vFLIP, and LANA proteins required for latent type infection is regulated by E1A. Transfection experiments in MV3 melanoma cells revealed activation of the LANAp by Ad5 E1A constructs containing an intact N terminus (aa 1-119). In particular, an Ad12 E1A mutant, Spm2, lacking six consecutive alanine residues in the "spacer" region activated the HHV-8 promoter about 15-fold compared to vector controls. In summary, we report the activation of the LANAp by E1A as a novel interaction of E1A with a viral promoter. These data may have relevance for the management of viral infections in immunocompromised patients. A role for E1A as a therapeutic in this context remains to be defined.

Cost-effectiveness of reduced follow-up in malignant melanoma.

BACKGROUND: Considerable variability exists in the extent and frequency of follow- up examinations for melanoma patients between different countries, generating significantly different total costs and uncertain clinical benefits. PATIENTS AND METHODS: We have analyzed the follow-up of melanoma patients under clinical and economic aspects based on the latest recommendations of the American Joint Committee on Cancer (AJCC) and the German Dermatologic Society (DDG) in the Düsseldorf cohort of 526 patients (stage IIII) during a 5-year follow-up period. Outcome measures were frequency of metastasis detection, most effective detection method, costs per detected metastasis and cost per quality-adjusted life year. RESULTS: Structured follow-up detected 17 recurrences in stages I-III. Physical examination and lymph node ultrasound were the only cost-effective methods at all stages, while laboratory studies were generally not cost-effective. The implementation of a reduced, yet medically adequate follow-up reducing chest X-rays, abdominal ultrasound examinations and eliminating blood tests in early stages yielded savings of more than 100,000 euro (120,000 $) annually at a tertiary care university hospital. CONCLUSION: The implementation of a reduced follow-up for melanoma patients seems not only medically justified but also economically required without adversely affecting patient outcome.