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W Sterry

Publications and source records attributed to W Sterry.

At least 55 records · Page 3Linked to original sources

The use of Toll-like receptor-7 agonist in the treatment of basal cell carcinoma: an overview.

Basal cell carcinoma (BCC) is a subtype of nonmelanoma skin cancer (NMSC), with an increasing incidence worldwide. Currently, excision of the tumour with histological control is the standard therapy. However, high incidence rates have led to concern about the economic burden imposed by BCC management in many countries. Imiquimod is a member of a novel class of immune response modifiers (IRM), which works by using the toll-like receptor (TLR)-7. Although the exact mode of action is so far unknown, it is suggested to induce the expression of different cytokines like interleukin (IL)-1, IL-6, IL-12, interferon (IFN)-alpha and tumour necrosis factor (TNF)-alpha, which stimulate or enhance both the innate immune system and the cell-mediated immune response. Pre-clinical studies have indicated the potential of this TLR-7 agonist for the treatment of precancers and tumours in humans. A number of Phase II trials have demonstrated the efficacy of imiquimod for the treatment of BCC, although the most appropriate dosing regimen is being confirmed in Phase III studies. Imiquimod 5% cream for the treatment of mainly superficial BCC appears to be an effective and well-tolerated treatment option.

Adjuvants, Immunologic↗

Viral warts in organ transplant recipients: new aspects in therapy.

The long-term success of organ transplantation depends on the prevention of allograft rejection and improvement in quality of life for the patients. This has been achieved through better immunosuppressive regimens with lower dosages and a new generation of immunosuppressive drugs. However, these immunosuppressive agents not only impair the patient's reactivity to the graft, but also to infectious organisms, thereby making them more susceptible to opportunistic pathogens. Because of this, organ transplant recipients are predisposed to epithelial malignancies and infections. The majority of transplant recipients will develop warts induced by human papillomavirus (HPV). Some of these viral warts may present with atypical histological features and may progress into squamous cell carcinomas. The risk for cutaneous cancers after transplantation is much higher than in the immunocompetent population. Current therapies for HPV-associated skin tumours mainly depend on the destruction of affected skin areas. These treatment modalities are of limited efficacy and are usually painful for the patients. A promising novel therapeutic agent is imiquimod, an immune response modifier. Clinical efficacy of imiquimod has been observed for different skin lesions, including viral warts in both immunocompetent and immunosuppressed patients.

Adjuvants, Immunologic↗

Induction of apoptosis by Toll-like receptor-7 agonist in tissue cultures.

Toll-like receptor (TLR)-7 agonists represent a new group of immune response modifiers, which include imiquimod and resiquimod (R-848). Topically applied imiquimod is used for the treatment of both external and perianal genital warts, and benign and malignant epithelial lesions. Based on the induction of interferons and other cytokines in vitro and in vivo, regression of epithelial lesions probably depends on induction of both innate and cellular immune responses. As clinical remission is not always associated with inflammation, other mechanisms may also be involved. Using two different assays for detection of apoptosis (TUNEL test and gel analysis of DNA fragmentation), we observed induction of apoptosis by imiquimod in human epithelial cell lines (HeLa S3) and keratinocytes (HaCaT, A431 cells), as well as in mouse fibroblasts (McCoy cells). These findings suggest that the mode of action of imiquimod to eliminate virus-infected, dysplastic or neoplastic epithelial cells may also include the induction of apoptotic processes.

Aminoquinolines↗

Cutaneous precancers in organ transplant recipients: an old enemy in a new surrounding.

Premalignant and malignant epithelial lesions are acknowledged as being the most frequent neoplasia in long-term immunosuppressed patients such as organ-transplant recipients. Paralleling the constant improvement in modern transplant techniques, their incidence increases together with the growing survival time post-transplantation, reaching 40% to 60% after 20 years. Against the background of lifelong immunosuppression, the impact of accepted cancer inducers and promoters such as ultraviolet radiation, oncogenic viruses and individual susceptibility has to be closely scrutinized. Precancerous lesions such as actinic keratoses in transplant patients progress more rapidly into squamous cell carcinomas, showing an increased tendency to metastasize. As it remains impossible to identify and consequently treat those lesions that may progress into invasive carcinoma, the best prophylaxis for nonmelanoma skin cancer in organ-transplant recipients may be the treatment of all existing precancerous lesions. As reduction of the immunosuppressive therapy is rarely practicable, other terms of prophylaxis and treatment, such as immune response modifiers, have to be considered.

Adjuvants, Immunologic↗

Subclinical activation of latent cytomegalovirus (CMV) infection and anti-CMV immune response in patients with atopic dermatitis.

BACKGROUND: Microbiological infections are considered to be of pathophysiological importance in atopic dermatitis (AD). As yet, no information is available regarding cytomegalovirus (CMV) infection in this disease. This, however, is of interest because of the high prevalence of latent infections in the general population, the frequent reactivation in inflammatory diseases, and the immunomodulating capacity of CMV. OBJECTIVES: To investigate the prevalence of latent CMV infection, the frequency of active CMV infection, and the immune response to CMV in patients with moderate to severe AD. Methods To detect active infection we analysed CMV antigen expression by peripheral blood mononuclear cells (PBMC) from 27 patients with moderate to severe AD in comparison with 53 healthy volunteers. We used three monoclonal antibodies recognizing different CMV-encoded antigens and immunocytological staining (alkaline phosphatase-antialkaline phosphatase technique). RESULTS: Patients with AD had a higher mean frequency of CMV-positive PBMC: 2.25 per 10 000 vs. 0.74 per 10 000 in controls (P = 0.001) as well as a higher incidence of CMV antigenaemia: 29.6% vs. 7.5% (P < 0.01). Seropositivity for anti-CMV IgG antibodies indicated subclinical activation of latent infection. Remarkably, a clearance of CMV antigenaemia was observed during anti-eczematous treatment. Significantly higher plasma levels of tumour necrosis factor-alpha, which is involved in CMV reactivation, and interleukin-12, which is crucial for an antiviral cellular immune response, were observed in AD patients in comparison with healthy volunteers. Furthermore, a significantly enhanced frequency of circulating activated HLA-DR+ T cells especially in CMV-seropositive AD patients (19.3% vs. 13.5% in seronegative AD patients vs. 10.2% in controls) suggested that the active CMV infection triggers a cellular immune response. This was also supported by a high frequency of CMV-specific interferon-gamma-producing T cells in CMV-seropositive patients with AD. CONCLUSIONS: Our data suggest that active, subclinical CMV infection is more frequent in patients with moderate to severe AD and may have immunopathophysiological relevance.

Adult↗

Reproducibility of a four-point clinical severity score for glabellar frown lines.

BACKGROUND: Focal injections of botulinum toxin A are used successfully for the treatment of hyperkinetic facial wrinkles. Efficacy can be measured by several methods. However, so far none has been investigated for its reproducibility. Objectives To investigate the reproducibility of a clinical 0-3 score for glabellar frown lines. METHODS: In the first part of the study, a standardized photographic documentation of glabellar frown lines was produced. Based on the results of this phase, a consensus atlas of glabellar frown lines was developed and participants were trained using this atlas. In the main study, 50 standardized photographs were shown on two consecutive days to 28 dermatologists. The reproducibility of the score was investigated by conventional kappa statistics. RESULTS: In the main study, we found an unweighted kappa according to Fleiss of 0.62 for interobserver reproducibility. Intraobserver reproducibility showed an unweighted kappa according to Cohen of between 0.57 and 0.91 for each observer, and a weighted kappa according to Cicchetti and Allison of between 0.68 and 0.94. CONCLUSIONS: The clinical 0-3 score for glabellar frown lines shows a good inter- and intraobserver reproducibility.

Female↗

Bexarotene--an alternative therapy for progressive cutaneous T-cell lymphoma? First experiences.

BACKGROUND: A standard therapy for advanced cutaneous T-cell lymphomas has not yet been defined. Bexarotene is a new retinoid x receptor-specific retinoid that has been approved for systemic second-line therapy for cutaneous T-cell lymphomas in the USA and Europe. In order to evaluate the efficacy of bexarotene in cutaneous T-cell lymphomas, a pilot trial was initiated. PATIENTS AND METHODS: In a pilot project 10 patients with advanced cutaneous T-cell lymphomas, who had received a variety of previous treatments, were treated with bexarotene at the departments of dermatology in Münster, Minden and Charité Berlin, Germany. The patients received bexarotene at a dose of 300 mg/m2 body surface daily. According to the percentage of tumour reduction and affected body surface, the response rates were divided in complete and partial remission, stable disease and progressive disease. Laboratory parameters i.e. cholesterol, triglycerides transaminases, T3, T4, and TSH were screened regularly. RESULTS: In 2 patients a short partial remission was achieved; however, after a few weeks progression followed. In 4 patients a lasting stabilisation was obtained. The other 4 patients showed a progressive disease during therapy. 6 patients developed hypertriglyceridemia with levels up to 2000 mg/dl; therapy had to be suspended in 3 patients because of these adverse drug events. CONCLUSION: Weighing benefits and risks, bexarotene can at present not be recommended as standard therapy in the treatment of patients with progressive cutaneous lymphomas.

Adult↗

No evidence of skin infection with Chlamydia pneumoniae in patients with cutaneous T cell lymphoma.

Recently, Chlamydia pneumoniae-specific DNA and antigens were reported in the skin of patients with Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphomas. In order to revalidate these data we analyzed skin sections of patients with MF for the expression of three different chlamydial antigens and C. pneumoniae DNA by immunohistochemistry and PCR according to previously described protocolls. Neither C. pneumoniae-specific DNA sequences nor antigens were detected in any of the skin biopses from 24 MF patients tested, suggesting that further studies are needed to establish any pathogenetic relevance of C. pneumoniae in MF.

Adult↗

Interleukin-10 therapy--review of a new approach.

Interleukin (IL)-10 is an important immunoregulatory cytokine produced by many cell populations. Its main biological function seems to be the limitation and termination of inflammatory responses and the regulation of differentiation and proliferation of several immune cells such as T cells, B cells, natural killer cells, antigen-presenting cells, mast cells, and granulocytes. However, very recent data suggest IL-10 also mediates immunostimulatory properties that help to eliminate infectious and noninfectious particles with limited inflammation. Numerous investigations, including expression analyses in patients, in vitro and animal experiments suggest a major impact of IL-10 in inflammatory, malignant, and autoimmune diseases. So IL-10 overexpression was found in certain tumors as melanoma and several lymphomas and is considered to promote further tumor development. Systemic IL-10 release is a powerful tool of the central nervous system to prevent hyperinflammatory processes by activation of the neuro-endocrine axis following acute stress reactions. In contrast, a relative IL-10 deficiency has been observed and is regarded to be of pathophysiological relevance in certain inflammatory disorders characterized by a type 1 cytokine pattern such as psoriasis. Recombinant human IL-10 has been produced and is currently being tested in clinical trials. This includes rheumatoid arthritis, inflammatory bowel disease, psoriasis, organ transplantation, and chronic hepatitis C. The results are heterogeneous. They give new insight into the immunobiology of IL-10 and suggest that the IL-10/IL-10 receptor system may become a new therapeutic target.

Animals↗

Malignant melanoma arising in a radiotherapy field: report of two cases and review of the literature.

We report 2 patients who developed melanoma or melanoma metastases in radiation fields 6 and 43 years after radiation therapy, respectively. One of the patients had received adjuvant hyperfractionated photon therapy for Ewing sarcoma, while the other patient had received X-ray therapy for a hemangioma. While postradiation secondary cancers with a long latency period are not uncommon, the development of melanoma is exceedingly rare.

Adult↗

Temporary shielding of hot spots in the drainage areas of cutaneous melanoma improves accuracy of lymphoscintigraphic sentinel lymph node diagnostics.

Detection of the "true" sentinel lymph nodes, permitting correct staging of regional lymph nodes, is essential for management and prognostic assessment in malignant melanoma. In this study, it was prospectively evaluated whether simple temporary shielding of hot spots in lymphatic drainage areas could improve the accuracy of sentinel lymph node diagnostics. In 100 consecutive malignant melanoma patients (45 women, 55 men; age 11-91 years), dynamic and static lymphoscintigraphy in various views was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour (31 patients) or the biopsy scar (69 patients, safety distance 1 cm). The images were acquired with and without temporary lead shielding of the most prominent hot spots in the drainage area. In 33/100 patients, one or two additional sentinel lymph nodes that showed less tracer accumulation or were smaller (<1.5 cm) were detected after shielding. Four of these patients had metastases in the sentinel lymph nodes; the non-sentinel lymph nodes were tumour negative. In 3/100 patients, hot spots in the drainage area proved to be lymph vessels, lymph vessel intersections or lymph vessel ectasias after temporary shielding; hence, a node interpreted as a non-sentinel lymph node at first glance proved to be the real sentinel lymph node. In two of these patients, lymph node metastasis was histologically confirmed; the non-sentinel lymph nodes were tumour free. In 7/100 patients the exact course of lymph vessels could be mapped after shielding. In one of these patients, two additional sentinel lymph nodes (with metastasis) were detected. Overall, in 43/100 patients the temporary shielding yielded additional information, with sentinel lymph node metastases in 7%. In conclusion, when used in combination with dynamic acquisition in various views, temporary shielding of prominent hot spots in the drainage area of a malignant melanoma of the skin leads to an improvement in the accuracy of identification and localisation of sentinel lymph nodes by lymphoscintigraphy.

Adolescent↗

New treatment modalities for basal cell carcinoma.

Basal cell carcinoma (BCC) is a subtype of nonmelanoma skin cancer (NMSC), a potentially fatal disease linked to overexposure to the sun during childhood. BCC has been associated with UV-induced mutations of the PTC and p53 tumor suppressor genes, and to polymorphisms in the melanocortin-1 receptor and XPD genes. Mortality rates due to BCC are low, but its increasing incidence and prolonged morbidity means the disease is costly to treat. Early recognition and effective treatment are therefore important, to reduce the incidence of BCC and lighten the economic burden of its management. This paper reviews current treatments for BCC, including excision and curettage, electrodessication, surgery, cryosurgery, radiotherapy, and treatment with 5-fluorouracil and intralesional/perilesional cytokines. It also deals with two new treatment modalities, photodynamic therapy and imiquimod 5% cream, an immune response modifier that effectively resolves BCC lesions.

Antineoplastic Agents↗

[Nutritional status of adult patients with atopic dermatitis].

Many atopic dermatitis (AD) patients follow elimination diets for long periods of time because of true or--even more often--suspected food allergies or hypersensitivities. In the present study we investigated the nutritional status of adult AD patients by evaluating food intake protocols followed by measuring different serum parameters. Evaluation of the food intake protocols over 3 days (n = 47) showed that the total calorie intake met recommended intake in 12 patients (group A), ranged between 75-100% of the requirements in 23 patients (group B) and was 50-75% in 12 patients (group C). The relative intake of different nutritional factors approached normal limits in group A and B; the intake of several of these factors was significantly decreased in group C. Various serum parameters in group C patients were different from those found in patients suffering from other chronic skin diseases. Taken together, our results show that a subgroup of AD patients have dietary habits which result in significant nutritional deficiency which are important for homeostasis. This indicates the necessity of professional guidance in these patients in order to only eliminate foods which have been proven to elicit adverse reactions by oral provocation tests.

Adolescent↗