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Wolfram Sterry

Publications and source records attributed to Wolfram Sterry.

At least 73 records · Page 4Linked to original sources
PubMed2004

[Online bedside teaching: multimedia, interactive and case-based teaching scenarios in dermatology].

The MeduMobile project or Mobiler Campus Charité was started in the beginning of 2003 to evaluate new, multimedia supported teaching and learning scenarios. The project focuses especially on acute and rare diseases to which students usually have are very limited access. During the teaching sessions the MeduOnCall team and the academic teacher communicate with the students who are equipped with individual notebooks through a wireless net. In dermatology the MeduMobile project focused in summer 2003 and winter 2003/2004 on bedside teaching. Despite some technical difficulties in the beginning the project was well received by teachers and students. The possibility of simultaneous online searches by Internet as well as the possibility to include photographs depicting the course of the skin disease was felt to be one of the main advantages of this project. Based on these positive experiences an attempt will be made to integrate the project further into the regular teaching of the Charite.

Case-Control Studies↗
PubMed2004

[Therapy options for psoriasis in childhood and adolescence].

Up to 30% of all psoriatic patients show their first symptoms during childhood and adolescence. In 1/4 of these children, psoriatic lesions appear within the first two years of life. The treatment of pediatric psoriasis differs considerably in several ways from that of adults. Not only the age and intensity but also physical development, prognostic criteria and social background should be considered. Standard procedures, clinical trials of high quality and therapeutic guidelines for psoriasis in childhood are still lacking. This review surveys the therapeutic management of pediatric and juvenile psoriasis. Current topical and systemic therapy options are critically reviewed. Prevention as well as enhancement of quality of life are also considered.

Adolescent↗
PubMed2004

Determination of the formation of the stratum corneum reservoir for two different corticosteroid formulations using tape stripping combined with UV/VIS spectroscopy.

BACKGROUND: The stratum corneum, the outermost layer of the skin, not only represents a barrier, but also a reservoir for topically applied substances. Both properties influence the penetration process, as does the vehicle. It determines the penetration pathway and the retention time of the topically applied substances. METHODS: Two commercial products (Temovate Cream and Temovate Emollient), both containing 0.05% clobetasol propionate, were applied on the inner forearms of healthy volunteers. 20 tape strips were removed from each treated skin area. The horny layer profile was determined measuring the absorption of the corneocytes at 430 nm. The concentration of clobetasol propionate on the individual tapes was then analyzed. RESULTS: We found differences in the reservoir formation depending on the formulation applied, which correlated to the biological response in the form of a blanching effect. CONCLUSIONS: The method applied is well-suited to determine the reservoir formation in the stratum corneum for topically applied substances.

Administration, Topical↗
PubMed2004

Genomic aberrations and survival in cutaneous T cell lymphomas.

Information on chromosomal aberrations in cutaneous T cell lymphomas (CTCL), is scarce. In this study, comparative genomic hybridization (CGH) was used to analyze chromosomal imbalances (CI) in 32 patients with CTCL. CI were detected in 21 patients (66%). Euchromatic loss (dim) was localized most frequently (>16%) at the chromosomal regions 17p (28%), 13q (25%), 10q (16%), and 6q (19%), and gain of chromatin (enh) at 7 (25%), 8q (25%), and 17q (16%). The pattern dim6q-enh7-enh8-dim13 was the most frequent combination of CI. The number of aberrations per tumor sample varied between 0 and 19 and correlated with clinical tumor stages: from none in stage Ia to 8.75+/-1.8 (mean+/-SEM) in stage IVa. CI occurred more frequently in aggressive subtypes (9.33+/-2.16) than in indolent (2.88+/-0.8) subtypes. A high number of CI (>/=5) was associated with shorter survival. Gain of chromatin in 8q and loss of 6q and 13q correlated with a significantly shorter survival, whereas the most frequently observed aberrations (loss in 17p and gain in 7) did not influence the prognosis. In summary, CGH analysis revealed a characteristic pattern of recurring chromosomal gains and losses in CTCL. The association of the imbalances with the clinical course of the disease suggests that genes encoded at these loci may influence tumor development and progression.

Aged↗
PubMed2004

Cellular coincidence of clonal T cell receptor rearrangements and complex clonal chromosomal aberrations-a hallmark of malignancy in cutaneous T cell lymphoma.

Detection of a clonal T cell receptor (TCR) gene rearrangement is used in the diagnosis of primary cutaneous T cell lymphomas (CTCL) whereas chromosomal aberrations serve as a diagnostic tool for leukaemias and nodal lymphomas. To what extent both approaches specify the same cell population remains unknown. We investigated the coincidence of TCR clonality with complex clonal chromosomal aberrations, indicating qualitative alteration of the affected cells, in 17 CTCL patients. Out of 41 skin, blood, and lymph node samples studied, 34 gave results in chromosome and TCR analyses. With 88%, most specimens revealed corresponding results by both techniques (27 of 34 clonal, three of 34 non-clonal). In two patients, analysis of micro-dissected cells demonstrated that neoplastic T cells bear both a dominant TCR rearrangement and a complex chromosomal aberration. The cutaneous clone was found in blood samples of 11 of 12 patients (including early stages), and investigation of follow-up skin and blood samples indicated persistence of the T cell clone in 11 of 14 cases. In conclusion, we show that dominant TCR clones and chromosomal clones converge in all stages of CTCL. These clones disseminate into blood and skin at early disease stages and persist despite therapy. The coexistence of a dominant TCR clone and a clonal chromosomal aberration can thus be used as a hallmark of malignancy.

Adult↗
PubMed2004

Correlation of psoriasis activity with abundance of CD25+CD8+ T cells: conditions for cloning T cells from psoriatic plaques.

The role of T cells in the pathogenesis of psoriasis is widely acknowledged. However, key aspects of their precise function in the disease as well as the relative pathogenic contribution of T-cell subsets are still unknown. T-cell clones have been isolated from psoriatic plaques but a study of conditions affecting the isolation and expansion of T-cell clones from psoriatic skin has not been reported to date. Here, we observe a correlation of disease activity with the frequency of the CD3(+)CD8(+)CD25(+) subset. We show that prolonged in vitro culture changes the phenotypic subset distribution of T-cell lines derived from psoriatic skin and that T-cell clones can be isolated by sorting of CD25(+) cells emigrated from skin fragments after 7 days. We evaluate various conditions affecting expansion of psoriatic T-cell clones in vitro and show that blocking apoptosis can facilitate proliferation of activated T-cell clones in vitro. Our results indicate a prominent role of the CD8(+)CD25(+) T-cell subset in disease pathogenesis and should be useful in the design of experiments aiming at a systematic analysis of the specificity of clones present in psoriatic plaques.

CD3 Complex↗
PubMed2004

Biology of tumor necrosis factor-alpha- implications for psoriasis.

Numerous recent investigations have pointed to a key role of the proinflammatory, pleiotropic cytokine tumor necrosis factor-alpha (TNF-alpha) in host defense and inflammatory processes. TNF overexpression has been found in lesional skin and in the circulation of psoriatic patients, and it was suggested that TNF-alpha is crucial in this and other immune diseases. Several approaches to inhibit TNF-alpha activity have been developed. These include three different neutralizing antibodies to TNF-alpha as well as three different soluble TNF-alpha receptors with characteristic properties designed to bind the 17-KDa soluble trimeric TNF-alpha and the 26-KDa membrane-bound form of TNF-alpha. Clinical trials have demonstrated significant antipsoriatic effects, and it is likely that blocking TNF-alpha will become an important therapeutic option. The data available from these trials contribute to further understanding of the disease by demonstrating the major role of TNF-alpha. An in-depth understanding of the regulation of TNF gene expression, protein production, receptor expression, and signaling pathways may lead to further, potentially important novel therapeutic strategies and antipsoriatic active small molecules, suitable for oral application in the future. Here we review the current knowledge of TNF biology, the approaches to inhibit TNF activity, and their clinical and immunological effects in psoriasis. In addition, the host-defense effects and chronic TNF-blocking activity are discussed.

Animals↗
PubMed2004

Human papillomaviruses in transplant-associated skin cancers.

BACKGROUND: Human papillomavirus (HPV) infection has been suggested to be involved in the development of nonmelanoma skin cancer, the most common malignancy after solid-organ transplantation. OBJECTIVE: The objective of this study was to analyze the prevalence of different HPV types in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) of transplant recipients and nonimmunosuppressed patients. METHODS: To include the complete spectrum of HPV types in skin lesions, a comprehensive polymerase chain reaction assay with five different primer combinations was used. RESULTS: For SCC, HPV DNA was detected more frequently in tumors of transplant recipients (12/16, 75%) than of nonimmunosuppressed patients (7/19, 37%). In contrast, the HPV detection rate was similar in BCC specimens (4/8 or 50% in transplanted patients; 27/56 or 48% in nonimmunosupressed patients). Overall, 22 different HPV types were identified. HPV types 5 and 8 were detected predominately in SCC from transplant recipients. The amount of viral DNA was slightly higher in SCC of transplanted than in nonimmunosuppressed patients, but much lower than in both cutaneous and genital warts. CONCLUSIONS: Cutaneous infections with HPV5 and HPV8 may represent an increased risk for SCC development in transplant recipients. The mechanisms by which these viruses may contribute to skin cancer development still remain unclear.

Adult↗
PubMed2004

Human papillomavirus and overexpression of P16INK4a in nonmelanoma skin cancer.

BACKGROUND: P16INK4a overexpression has been identified as a specific biomarker in high-risk human papillomavirus (HPV)-infected cervical (pre)cancer lesions. OBJECTIVE: To evaluate the overexpression of this cyclin-dependent kinase inhibitor in skin tumors depending on HPV infections, we analyzed normal skin, benign skin disease, and skin cancer specimens. METHODS: Biopsies of 23 patients with normal histology (3), psoriasis (2), verrucae vulgaris (2), actinic keratoses (5), squamous cell carcinoma (SCC) in situ (3), Bowen's carcinoma (1), and SCC (7) were analyzed. Specimens of 23 patients were immunostained using the monoclonal antibody E6H4 specific for p16INK4a. HPV status was assessed by a polymerase chain reaction (PCR) system to detect all currently known HPV types. MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis. Only beta-globin-positive patients were included in this study. RESULTS: HPV DNA was detected in all actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC, in 50% (one of two) of verrucae vulgaris, in 66% (two of three) of normal skin, and in none of two psoriasis. P16INK4a expression was not detected in normal skin, psoriasis, and verrucae vulgares. Overexpression of p16INK4a was detected in a subset of dysplastic cells (10% to 80%) of all skin (pre)cancer lesions such as actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC infected with HPV independent of sun exposure. CONCLUSION: P16INK4a appears to be overexpressed in a portion of dysplastic cells from actinic keratoses and SCC. Further studies to examine the association of HPV infection and the overexpression of p16INK4a are warranted.

Aged↗
PubMed2004

Comparative epidemiology and pathogenic factors for nonmelanoma skin cancer in organ transplant patients.

BACKGROUND: Organ transplantation has been performed for almost 40 years with steadily increasing success regarding long-time survival of the graft as well as quality of life for the patient. An increase of skin cancers as a consequence of the lowered cellular immune response seems to parallel the overall increased survival rate of organ transplant recipients. Against the background of chronic immunosuppression, known risk factors like the amount of sun exposure before and after transplantation and oncogenic viruses as well as the genetic background and place of residence (latitude) are strongly related with the increased skin cancer incidence. The goal of this review is to compare the epidemiologic prevalence of nonmelanoma skin cancer between various geographic locations and to highlight pathogenesis factors. METHODS: This study was based on a review of the current literature. RESULTS: The increasing incidence of nonmelanoma skin cancer paralleling a prolonged survival of patients after organ transplantation represents a significant reason for morbidity and long-term mortality in organ transplant recipients worldwide. The incidence of nonmelanoma skin cancer in liver, kidney, and heart transplant recipients varies from 1.5% to 22%, 2% to 24%, and 6% to 34%, respectively, within 5 years of transplantation depending on geographic location and other pathogenesis factors. Ultraviolet radiation (UVR) as well as immunosuppressant therapy are crucial risk factors regarding the induction and progression of skin cancer. UVR is related to the induction of DNA damage as well as interference with Langerhans cell antigen presentation and a TH1-TH2 shift induced via release of IL-10. Whereas the overall duration of immunosuppression and the accumulative dosage applied are relevant measures in the pathogenesis of an increased tumor risk, individual differences between specific immunosuppressive agents are more difficult to assess. CONCLUSIONS: Multiple international studies assess risk factors and pathophysiology of skin cancer in organ transplant patients, with variable results in the literature. Large multicenter studies with thorough multivariant analysis may provide useful information for center-independent analysis of pathogenesis factors for transplant-related skin cancer.

Australia↗
PubMed2004

In vivo determination of skin surface topography using an optical 3D device.

BACKGROUND/PURPOSE: Topography of the skin surface is a mirror of the functional skin status. Therefore, its evaluation is of great interest for dermatological research. In the present study, a new optical measuring system was applied to evaluate human skin surface topography in vivo and non-invasively, in order to determine elastotic and mimic wrinkles dependent on age, body site and therapy. METHODS: The measurements were performed on the back (n=5), the flexor forearm (n=14) of volunteers in different age groups and on the face of women (n=4) participating in an anti-wrinkle study. The evaluation of the three-dimensional-profiles was performed determining skin surface parameters (mean roughness (R(a)), mean depth of roughness (R(z)), maximum roughness (R(m)) and waviness (W(t))) and applying Fourier analysis. RESULTS: Significant increases in all surface parameters were obtained on the forearms with increasing age. Differences between the surface topographies of forearm and back were only expressed by the waviness and the Fourier analysis. The treatment with botulinum Toxin A led to a diminution of mimic wrinkles as reflected by the furrow profiles. CONCLUSIONS: The results show a significant dependence of the skin surface topography on the age of the volunteer and the body site measured. Particularly the waviness, the Fourier analysis and the furrow profiles reflect such dependencies. The system used also fulfils the requirements for the testing of therapies, as was demonstrated by the reduction of mimic wrinkles after treatment with botulinum Toxin A.

Adult↗
PubMed2004

New and emerging vaccination strategies for prevention and treatment of dermatological diseases.

Accelerated by the rapid advancements of our understanding of the molecular and cellular pathology of diseases and of the components and mechanisms of cellular and humoral immune responses, new vaccination strategies are being developed and explored for treatment and prevention of infectious diseases, cancer, autoimmune disorders and allergies. Many newly developed vaccination strategies are already in clinical trials, some with very promising results. Although most of these strategies are still at very early stages of their development, it is foreseeable that vaccination will evolve to play an important role in prevention, treatment and management of all the above classes of diseases.

Adjuvants, Immunologic↗
PubMed2004

The glucocorticoid receptor as target for classic and novel anti-inflammatory therapy.

Glucocorticoids are well known for their potent anti-inflammatory and immune-suppressive actions. Their clinical usefulness remains limited due to serious side effects that have necessitated a search for ways of improving their benefit-risk ratios. Mechanistically, glucocorticoids function by interacting with an intracellular receptor, the glucocorticoid receptor, a ligand-regulated transcription factor that positively or negatively alters the expression of specific genes. While it is well accepted that distinct negative regulatory action of this receptor forms the basis of the desired anti-inflammatory effects of glucocorticoids, not much is known about the function of the receptor that contributes to its side effects. The fact that a number of cellular metabolic control genes are positively regulated by glucocorticoids makes positive regulation of gene expression an attractive mode of action for the adverse effects. Positive regulation of gene expression by glucocorticoids, however, occurs through different mechanisms and in cell-type specific manner making it difficult to predict its possible biological effects in one single assay procedure. Recent advances in the molecular action of the receptor are gradually revealing different assays and important characteristics that can be put together in determining the physiological consequences of the different transactivation functions of the glucocorticoid receptor. These will provide invaluable source of information for the search of glucocorticoid receptor agonists with potent anti-inflammatory but reduced side effects.

Animals↗
PubMed2004

Interleukin-10: an important immunoregulatory cytokine with major impact on psoriasis.

Interleukin (IL)-10 is a pluripotent cytokine with effects on numerous cell populations, in particular circulating and resident immune cells as well as epithelial cells. With its potent immunoregulatory capacities its main biological function seems to be the limitation and termination of inflammatory responses. Thus its low level expression found in psoriasis may have pathophysiological relevance for this immune disease. Remarkably, induction of IL-10 expression was found by conventional antipsoriatic therapies, supporting the hypothesis that IL-10 may be a key cytokine in psoriasis and that application of this cytokine itself may have therapeutic effects. In first clinical trials in patients with established psoriasis IL-10 showed moderate antipsoriatic effects and was well tolerated. Moreover, long term application in psoriatic patients remission showed that IL-10 therapy decreases the incidence of relapse and prolongs the disease free interval. The immunological effects observed during these clinical studies together with in vitro observations suggests that IL-10 exerts its antipsoriatic activity by effects on different cell populations including antigen presenting cells and T-cells (lasting type 1/ type 2 cytokine balance shift), but not through direct effects on keratinocytes. In conclusion IL-10 seems to have major importance in psoriasis. Further investigations, in particular multicenter, placebo-controlled, double blind trials are required to fully determine whether IL-10 application will become a successful antipsoriatic therapy.

Adjuvants, Immunologic↗
PubMed2003

Influence of fast lymphatic drainage on metastatic spread in cutaneous malignant melanoma: a prospective feasibility study.

The concept of sentinel lymph node biopsy in cutaneous malignant melanoma is widely established. Preoperative cutaneous lymphoscintigraphic mapping is a reliable method for identifying the nodal basins at risk of metastases in melanomas. In this prospective study we investigated the correlation between the scintigraphic appearance time and the metastatic involvement of sentinel lymph nodes. In 276 malignant melanoma patients (137 women, 139 men; age 16-93 years), dynamic and static lymphoscintigraphy was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour or biopsy scar. Analysis of dynamic scans primarily focussed on the appearance time of sentinel lymph nodes. Sentinel lymph node visualisation </=20 min post injection was defined as fast drainage, and visualisation >20 min as slow drainage. Fast lymphatic drainage was found in 236 patients, of whom 34 (14.4%) had sentinel lymph node metastases. Twenty-two patients showed hybrid (fast and slow) lymphatic drainage, and eight (36.4%) of them had sentinel lymph node metastases. Seven of the latter demonstrated fast lymphatic drainage, while one showed one positive sentinel lymph node with fast and another with slow drainage. The melanomas of 18 patients demonstrated exclusively slow lymphatic drainage, in all cases without sentinel lymph node metastases. This prospective study indicates that the scintigraphic appearance time of sentinel lymph nodes seems to be a clinically relevant factor for prediction of metastatic spread of cutaneous malignant melanoma. Larger numbers of patients need to be examined to truly assess the benefit of the scintigraphic appearance time compared with other predictors of sentinel lymph node tumour positivity.

Adolescent↗
PubMed2003

Anti-tumor immune responses and tumor regression induced with mimotopes of a tumor-associated T cell epitope.

Mimotopes provide an alternative to natural T cell epitopes for cancer immune therapy, as they can recruit and stimulate T cell repertoires that deviate from the repertoires engaged with the tumor and exposed to disease-related immune suppression. Here, mimotopes of a shared tumor-associated T cell epitope in cutaneous lymphoma were tested for their capacities to induce clinical and immunological responses in cancer patients. The mimotope sequences had been determined by a combinatorial peptide library approach without knowledge of the corresponding natural tumor-associated antigen. Vaccination with these mimotopes together with helper T cell-inducing antigens led to complete tumor remission in the two patients tested. After each booster vaccination, enhanced frequencies of mimotope-specific CD8+ T cells were detected in the peripheral blood of the patients, and the CTL proved to be cytotoxic and tumoricidal when tested in vitro. These data provide a first indication of clinical efficacy of mimotopes in cancer patients.

Cancer Vaccines↗