Tino Wetzig

Detection of human soluble Thy-1 in serum by ELISA. Fibroblasts and activated endothelial cells are a possible source of soluble Thy-1 in serum.

Abstract. The functions of Thy-1, a 35-kDa cell-surface glycoprotein, and its natural ligand are still unknown. Anchoring to the membrane via linkage to phosphatidylinositol (PI) raises the possibility of cleavage off the membrane by PI-specific phospholipases. Soluble Thy-1 (sThy-1) could interfere with the binding of the unknown natural ligand followed by regulation of different cell functions. In this study we established an enzyme-linked immunosorbent assay (ELISA) to measure and quantify sThy-1 in serum and wound fluid. Recombinant human Thy-1 (rhThy-1) was expressed in Drosophila S2 cells, purified from culture supernatant and used as standard for quantitation of sThy-1 by the ELISA technique. There were no differences in sThy-1 levels in serum of healthy donors and patients with systemic sclerosis, leg ulcers, or rheumatoid arthritis, respectively, detected by ELISA. In contrast, at the local site of inflammation, in wound fluid of venous leg ulcers and in synovial fluid from joint puncture, we found strongly elevated levels of sThy-1 compared with sThy-1 in the serum of the same patient. Thy-1 is expressed in humans on brain cells, fibroblasts, a subpopulation of CD34+ blood stem cells, and possibly activated human dermal microvascular endothelial cells. In this study, we never found Thy-1 mRNA or protein expression in resting endothelial cells as shown by reverse transcriptase polymerase chain reaction (RT-PCR) and flow-cytometry. Thy-1 expression could be induced on endothelial cells by phorbol myristate acetate and to a lesser extent by tumor necrosis factor-α (TNF-α). In situ, monoclonal antibodies to Thy-1 did not stain endothelial cells in normal skin, whereas endothelial cells in the synovial membrane of rheumatoid arthritis patients and endothelial cells surrounding melanoma express Thy-1. In summary, our data indicate that Thy-1 is present in soluble form in serum. Furthermore, Thy-1 seems to be a marker for endothelial cell activation. Therefore, activated endothelial cells as well as fibroblasts might be a possible source of sThy-1.

Trichophyton species of Arthroderma benhamiae - a new infectious agent in dermatology

In Germany, infections due to the zoophilic dermatophyte Trichophyton (T.) species of Arthroderma benhamiae are being more frequently diagnosed. The source of infection of this emerging pathogen overlaps with that of the zoophilic species T. interdigitale. The most common source are guinea pigs. T. species of Arthroderma benhamiae causes inflammatory dermatophytosis in children and adolescents. In addition to tinea capitis, it may cause both tinea corporis, tinea manus and frequently tinea faciei. In Germany, T. species of Arthroderma benhamiae is a frequent zoophilic dermatophyte, which in regions is probably more frequent than Microsporum canis. The mycological identification of the isolates with their yellow stained colonies is based on their macroscopic and microscopic features. However, some exhibit colony features consistent with those of T. interdigitale. These strains only can be identified unambiguously by means of molecular techniques. Using detection methods such as PCR‐ELISA or real‐time PCR, the dermatophyte can be identified directly from clinical material. Sequencing of the internal transcribed spacer region (ITS) of the ribosomal DNA has been approved as culture confirmation test for T. species of Arthroderma benhamiae. In addition, matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI TOF MS) is useful. Widespread dermatophytosis due to T. species of Arthroderma benhamiae, in particular of tinea capitis, requires oral antifungal agents. Terbinafine is most effective, alternatives are fluconazole and itraconazole.

Surgical excision of basal cell carcinoma with complete margin control: outcome at 5-year follow-up.

Background: The incidence of skin cancer and especially basal cell carcinoma (BCC) has increased in the last few decades. The gold standard of care is usually a surgical excision, but it also has the risk of local recurrence depending on tumor characteristics. Objectives: We analyzed the 5-year cure rates after surgical excision of BCC with complete margin control using paraffin-embedded sections. Methods: A retrospective analysis of 671 patients (45.3% male, 54.7% female) with 777 primary and 85 with recurrent BCC were collected during 2001–2003. All patients underwent surgery with complete margin control using paraffin-embedded sections. When the histological examination revealed a positive margin, another surgical step was performed in the area of residual tumor. Results: Five-year follow-up examinations were possible in 630/862 (73.1%) of patients with BCC. In the group with primary BCC (n = 562), 3 tumor recurrences (0.5%) were identified; in the group with recurrent BCC (n = 68), 2 tumor recurrences (2.9%) were seen, resulting in an overall 5-year recurrence rate of 0.8% for all patients with BCC. The mean tumor recurrence time after surgery was 36.6 months. Conclusion: Local complete tumor resection confirmed by complete margin control using paraffin-embedded sections can achieve excellent cure rates for both primary and recurrent BCC.

Complete remission of cutaneous and subcutaneous melanoma metastases of the scalp with imiquimod therapy.

Multiple cutaneous and subcutaneous melanoma metastases represent a therapeutic challenge. A 63‐year‐old man presented with multiple cutaneous and subcutaneous melanoma metastases on his right parieto‐occipital region that appeared ten weeks after surgical excision of the primary tumor. Staging showed no further metastases. Because of the large area of cutaneous metastatic spread, the location and the limited possibility of a complete excision, we decided to begin immunomodulatory therapy with imiquimod applied for eight hours daily five days a week. After six weeks of imiquimod monotherapy, a partial remission of the cutaneous metastases had occurred. After 17 months, the remission of these metastases was complete. Four months later the patient is still free of cutaneous, visceral, cerebral and lymph node metastases.

Serum levels of soluble Fas/APO-1 receptor are increased in systemic sclerosis

Abstract It has been suggested that rheumatic diseases may result from a deficit in Fas-mediated T-cell apoptosis. Recent studies have demonstrated increased soluble Fas in sera from lupus erythematosus patients. We were interested to determine whether elevated soluble Fas levels are associated with systemic sclerosis. Soluble Fas levels were retrospectively assayed using a sandwich enzyme-linked immunosorbent assay in serum from 30 patients with systemic sclerosis and 15 normal controls. Hospital medical records were retrospectively reviewed for clinical and laboratory characteristics of the patients. Soluble Fas levels were analysed in subsets of patients with limited (lcSSc) versus diffuse cutaneous systemic sclerosis (dcSSc) and correlated with inflammatory activity. In systemic sclerosis soluble Fas serum levels (lcSSc, 2.19 ± 0.71 ng/ml, dcSSc 2.53 ± 1.37 ng/ml) were significantly higher than in normal controls (1.26 ± 0.36 ng/ml). However, there were no significant differences in soluble Fas levels between lcSSc and dcSSc and poor correlation between soluble Fas levels and inflammatory activity status. Detection of elevated soluble Fas might serve as a clinical marker for immunological dysregulation in systemic sclerosis, but not for inflammatory disease activity.

Elevated sex steroid hormones in great saphenous veins in men

INTRODUCTION High serum levels of estradiol are associated with clinical evidence of varicose veins in women; however, the relationship between serum sex steroid hormones and varicose veins in men is unclear. To address this issue, serum levels of testosterone, estradiol, and androstenedione were determined in the great saphenous (GSV) and cubital veins of men with varicose veins. Messenger RNA (mRNA) expression of sex steroid hormones, metabolizing enzymes, and their receptors was investigated in tissue samples of leg veins. METHODS This prospective study included 40 men, comprising 20 with varicose veins and reflux of the GSV (VM) and 20 with healthy veins (HM). All limbs were assessed by duplex ultrasound scanning of selected superficial and deep leg veins. Blood samples were taken from the cubital vein and from the GSV. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis for sex steroid hormones, their metabolizing enzymes, and receptors in saphenous veins was performed in tissue samples of varicose (n = 6) and healthy veins (n = 6). RESULTS The VM group had significantly higher (P < .001) mean levels for serum testosterone (44.9 nmol/L; range, 8.8-225.1) and estradiol (242.2 pmol/L; range, 79-941) in varicose saphenous veins compared with cubital veins (testosterone, 15.5 nmol/L; range, 8.4-23.3; estradiol, 93.2 pmol/L; range, 31-147). Moreover, significantly (P < .001) higher mean serum estradiol levels (133.2 pmol/L; range, 63-239) were detected in the saphenous veins of the HM group compared with cubital veins (88.15 pmol/L; range, 37-153). Both groups had similar blood counts and serum androstenedione levels in the upper and lower extremity. Interestingly, qRT-PCR revealed that the mRNA expression of 5alpha-reductase type 1, 5alpha-reductase type 2, 17, 20 lyase, 17beta-hydroxysteroid dehydrogenase (17beta-HSD), aromatase and 3beta-HSD type 2, androgen and estrogen receptor 1 was down-regulated (P < .05) in all samples of varicose veins vs veins obtained from healthy men. CONCLUSION Elevated serum estradiol and testosterone levels were detected in men with varicose veins and reflux in the GSV compared with the patients own arm veins. Enzymes and hormonal receptors involved in steroid metabolism were down-regulated in patients with GSV reflux and varicose veins, suggestive of a negative feedback regulation. These data support the notion of a possible causal relationship between sex steroids and varicose veins in men.

Local anesthesia in dermatology

Local and regional anesthetic procedures are an integral part of daily dermatological practice. Safe and effective analgesia in skin and soft tissues is crucial for otherwise painful diagnostic or therapeutic interventions. Tumescent local anesthesia allows for pain‐free interventions that previously had to be done by using general anesthesia. Older patients with multiple co‐morbidities are especially suited for local anesthetic procedures, because they may significantly reduce surgical risks. For dermatologists, the knowledge of mode of action and toxicity of local anesthetics, as well as the emergency management of their potential complications, is essential.

Treatment of basal cell carcinoma

Basal cell carcinoma is the most common tumor in Central Europe, the U.S. and Australia. The increasing incidence of basal cell carcinoma presents the health care system, especially dermatology, with great challenges. In recent years new options for treating basal cell carcinoma have become available, enriching our therapeutic options. We review the current status of each of these treatment approaches.

Foam sclerotherapy — A possible option in therapy of varicose veins

The therapy of varicose veins is multimodal and depends on the individual clinical findings. In addition to compression therapy, invasive approaches for elimination of reflux for the treatment of varicose veins are available, such as surgical and interventional methods and sclerotherapy. The administration of a scle‐rosing agent into a varicose vein results in an occlusion of the treated vein. Recently the use of foam sclerotherapy had a renaissance. Several studies have documented the efficacy of foam sclerotherapy in selected patients. The possibility of treating patients in an outpatient setting, with low costs and rapidly, makes foam sclerotherapy very attractive compared to invasive and minimally invasive methods. However long‐term follow‐ups in properly controlled randomized trials are needed before foam sclerotherapy can be recommended as a routine procedure. This paper introduces the method and the treatment possibilities with foam sclerotherapy in chronic venous insufficiency.

No clinical benefit of preoperative fluorescence diagnosis of basal cell carcinoma localized in the H-zone of the face.

Background  Basal cell carcinoma (BCC) is the most common malignant skin carcinoma. Fluorescence diagnosis (FD) has been suggested as a promising method for noninvasive detection of subclinical tumour cell dissemination in BCC.