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Biomedical subjects

Wolfram Sterry

Publications and source records attributed to Wolfram Sterry.

105 records · Page 6Linked to original sources

Immunomodulation by interleukin-10 therapy decreases the incidence of relapse and prolongs the relapse-free interval in Psoriasis.

The ability of interleukin-10 therapy to reduce the severity of exacerbated psoriasis has been demonstrated recently. Considering the immunobiologic properties of this cytokine we investigated the effects of long-term interleukin-10 application on the immune system and duration of psoriasis remission. We performed a placebo-controlled, double-blind, phase II trial using interleukin-10 in patients with chronic plaque psoriasis in remission. Patients received subcutaneous injections with either interleukin-10 (10 microg per kg body weight; n = 7) or placebo (n = 10) three times per week until relapse or study termination after 4 months. The treatment was well tolerated. In the placebo group almost all patients (90%) showed a relapse during the observation period. In contrast to this, only two of seven patients (28.6%) relapsed in the interleukin-10-treated group. Kaplan-Meier analysis revealed a significantly lower relapse incidence in the interleukin-10 than in the placebo group (p = 0.02). The mean relapse-free interval time was 101.6 +/- 12.6 d in the interleukin-10 group in comparison with 66.4 +/- 10.4 d in the placebo group. Immunologic activity of interleukin-10 application was indicated by an increase in soluble interleukin-2 receptor plasma levels and higher ex vivo interleukin-4 secretion capacities. Remarkably, a significant negative correlation was demonstrated between the interleukin-4 secretion capacity and Psoriasis Area and Severity Index score (r = -0.36, p < 0.01). Our data suggest that interleukin-10 therapy is immunologic effective, decreases the incidence of relapse and prolongs the disease-free interval in psoriasis. Its value should be further determined in larger trials and for the prevention of re-exacerbation of other inflammatory disorders with a similar immunologic profile.

Adult↗

The role of ultrasound in detection and management of regional disease in melanoma patients.

Melanoma follow-up programs are directed towards early detection of tumor recurrence. Because the majority of first relapses occur in the regional lymph node area, special focus is placed on this region using various techniques in addition to physical examination. During the last several years, particularly ultrasound B-scan has evolved as a technique of major importance for detection of such regional melanoma recurrences. The technique shows high sensitivity and specificity, discriminating regional or subcutaneous melanoma metastases from nonspecific nodes. Furthermore, suspicious findings can be evaluated quickly and reliably by the minimally invasive technique of ultrasound-guided fine-needle aspiration cytology (FNAC). For regional metastases located deeply or close to vulnerable structures, the new method of ultrasound-guided anchor-wire-marking facilitates subsequent surgery. In summary, ultrasound B-scan has become an essential technique in the follow-up of melanoma patients.

Biopsy, Needle↗

Carcinoma arising in a proliferating trichilemmal cyst expresses fetal and trichilemmal hair phenotype.

Carcinomas that arise in a proliferating trichilemmal cyst (PTC) have been described under a variety of names. Monoclonal antibodies (mAbs) indicating follicular differentiation have become available and were used here in two rare tumors with uncommon biologic behavior. To further elucidate the histogenesis of carcinomas arising in a PTC, mAbs to hair follicle stem cells and to hair follicle differentiation-specific cytokeratins (mAbs to cytokeratin [CK] 7, CK8, CK18, and CK19 as well as mAbs to CD8/CK15 and CD34) were studied on paraffin-embedded sections of two cases of carcinoma arising in a PTC, one anaplastic carcinoma, and one poorly differentiated squamous cell carcinoma (SCC). For comparison, concurrent PTCs and trichilemmal cysts as well as four SCCs from controls were studied. The anaplastic carcinoma showed expression of CK7, indicating a fetal hair root phenotype, and expression of CD34, indicating trichilemmal differentiation. In contrast, the poorly differentiated SCCs as well as the control SCCs stained negative for most of the mAbs applied. Expression of fetal and trichilemmal hair follicle phenotypes suggests differentiation from hair stem cells and might explain differences in biologic behavior.

Aged↗

A T-cell receptor gamma polymerase chain reaction assay using capillary electrophoresis for the diagnosis of cutaneous T-cell lymphomas.

Detection of clonal T-cell receptor gamma rearrangements by polymerase chain reaction (TCRgamma PCR) followed by high-resolution electrophoresis has now become a valuable tool in the diagnosis of cutaneous T-cell lymphoma (CTCL). The identification of clonal TCRgamma PCR products by fluorescent fragment analysis (FFA) on a capillary DNA sequencer is described here and compared with an established hetero-duplex temperature gradient gel electrophoresis (HD-TGGE). Of 55 CTCL derived lesional skin samples, clonality was obtained in 46 samples by FFA (83.6%) and in 45 samples by HD-TGGE (81.8%). Of 35 control skin specimens from various nonmalignant dermatoses, two samples (pityriasis lichenoides chronica) showed clonality by both methods, one sample (chronic dermatitis) only by FFA. The sensitivity of FFA was established using three clonal T-cell lines and peripheral blood mononuclear cells. The detection limit for clonal material was approximately 1% to 2.5% in mixtures of DNA and 1% to 3% in cell dilutions. For cell dilution series, we confirmed a linear correlation between the clonal/polyclonal peak-size ratios and the portion of clonal cells up to about 10%. Thus, the initial ratio between mono-and polyclonal template is correctly displayed by FFA within that concentration range. In conclusion, FFA on capillary DNA sequencer is a well-suited separation technique in TCRgamma PCR-based clonality analysis also exhibiting quantitative properties.

Clone Cells↗

Report of a case of Schnitzler's syndrome treated successfully with interferon alpha 2b.

Schnitzler's syndrome (SS) is characterized by the association of generalized chronic urticaria, osteocondensation and monoclonal IgM gammopathy. Nonsteroidal anti-inflammatory drugs and systemic steroids are the most promising treatments. In our patient, they were ineffective. By contrast, during the follow-up period of 18 months, interferon alpha(2b) therapy (IFN-alpha) relieved the patient from its urticarial lesions and bone pain. IFN-alpha was tried to be stopped twice: each time, relapse of urticaria was noticed and, each time, the cutaneous lesions disappeared after IFN-alpha had been reintroduced. Furthermore, our observation supports the idea of the interleukin (IL)-1-mediated pathogenesis of SS as IFN-alpha induces high levels of IL-1 receptor antagonists. IFN-alpha could be an alternative treatment in disabling SS resisting other drugs.

Bone and Bones↗

Experimental therapies for psoriasis.

There is a high medical need for better therapies for psoriasis. Based on new insight into the pathophysiology of this frequent immune disease, a number of novel systemic immunomodulatory therapies are currently in clinical development. These include approaches targeting antigen presentation and costimulation, T cell activation and leukocyte adhesion, action of proinflammatory mediators, and modulating the cytokine balance. Although mainly only preliminary data are available so far, these trials contribute to a further understanding of the disease and will eventually lead to new therapeutic options for psoriasis. Moreover, since psoriasis can be considered as a visible model disease for T cell-mediated disorders characterized by a type 1 cytokine pattern in general, such approaches may have impact for other immune disorders as well. Here we review the rationale and the initial clinical data of these important recent experimental therapies.

Antibodies, Monoclonal↗

Diffuse normolipemic plane xanthoma in a 9-year-old boy.

Normolipemic plane xanthoma normally occurs in adults. We report the atypical instance of a 9-year-old boy who developed disseminated, flat, yellow-brown plaques up to 2 to 3 cm without any complaints. The histology showed the hallmarks of xanthoma, including the presence of CD68+ foam cells and Touton giant cells. No systemic involvement or lipid disorders were evident. It is important to perform regular follow-up of these patients because normolipemic plane xanthoma often precedes myeloproliferative disorders such as leukemia, paraproteinemia, or lymphoma.

Antigens, CD↗

Influence of nonhomogeneous distribution of topically applied UV filters on sun protection factors.

The aim of the present study is the development of a method to determine quantitatively in vivo the influence of homogeneity of the distribution of sunscreen containing UV filters on the sun protection factor (SPF). The SPF of a sunscreen applied either topically or inside an optical cell (pure or in a solvent) fixed above the skin is determined in vivo. In both cases, in vivo measurements using the erythema formation are carried out. Identical optical parameters of the skin are realized in both experiments. In addition, both in vitro (using tape stripping) and in vivo microscopic measurements are performed to analyze the homogeneity of distribution of the topically applied substances. An SPF of 8 is measured in the experiment applying the UV filters topically, whereas this value increases by a factor of 10 if the same amount of filter substances is distributed homogeneously in solution inside the optical cell. Tape strips removed from skin treated with the sunscreen reflect the inhomogeneous distribution of the topically applied substances on the skin. The direct correlation of homogeneity of distribution with the SPF opens up the possibility to increase the SPF by optimizing the formulation.

Administration, Topical↗

Determination of penetration profiles of topically applied substances by means of tape stripping and optical spectroscopy: UV filter substance in sunscreens.

Penetration profiles of topically applied drugs and cosmetic products provide important information on their efficacy. The application of tape stripping in combination with UV/VIS spectroscopy is checked to determine the local position of topically applied substances inside the stratum corneum, the penetration profile. The amount of corneocytes removed with each tape strip is quantified via the particle-dependent absorption, the pseudoabsorption, in the visible spectral range. The concentration of a typical UV filter substance, 4-methylbenzylidene camphor, is determined by optical spectroscopy using the tape strips removed originally. In this case, a time-dependent increase in the absorbance must be taken into account. Laser scanning microscopic investigations confirm that the nonhomogeneous distribution of the filter substance, on the strips, can explain this spectroscopic behavior. When reaching a homogeneous distribution, the UV spectroscopic signal reflects the correct concentration. These spectroscopic values are compared with high performance liquid chromatography (HPLC) data. The values obtained with both methods for the concentrations of 4-methylbenzylidene camphor are in good agreement. The data obtained are used to illustrate the determination of a penetration profile of a UV filter substance. The results demonstrate that the described protocol is well suited to characterize, in a simple manner, topically applied substances that have a characteristic UV/VIS absorption band.

Administration, Cutaneous↗

Optical investigations to avoid the disturbing influences of furrows and wrinkles quantifying penetration of drugs and cosmetics into the skin by tape stripping.

Furrows and wrinkles, as typical structures of human skin, represent a reservoir for topically applied substances. This reservoir can influence penetration experiments of topically applied substances into the stratum corneum by tape stripping. Optical methods such as laser-scanning microscopy, optical coherent tomography, and the microscopical investigation of histological sections obtained by biopsies were used to check a special protocol, which avoids these potential disturbances. The use of a transparent adhesive film with high flexibility and the realization of an intense contact to the stretched skin by pressing the tape with a roll, moved laterally on the tape, are the prerequisites to obtain correct data. The application of this experimental technique and the performance of tape stripping allow the determination of the horny layer profile and the local distribution of topically applied substance, undisturbed by the characteristic structure of the natural skin. These results demonstrate that the presented tape stripping procedure is a valuable tool to determine, quantitatively, the penetration and the bioavailability of drugs and cosmetics inside the human stratum corneum, in relation to the horny layer profile.

Artifacts↗

Comparison of blood flow to the cutaneous temperature and redness after topical application of benzyl nicotinate.

The topical application of drugs, such as nicotinates, affects cutaneous blood flow. Such a biological response, which is dependent on the drug and the individual, can be measured noninvasively using laser Doppler flowmetry. We illustrate the kinetics of vasodilation caused by topically applied benzyl nicotinate using a new frequency-selective laser Doppler flowmeter. This flowmeter measures the blood flow in the superficial dermal plexus and the deeper lying larger capillaries simultaneously and indirectly by determining the flow velocity. Both sets of data are compared with the skin temperature and redness. Four biological parameters are measured consecutively on a skin area treated with gel containing benzyl nicotinate and on an untreated control area. A linear relationship between both blood flows is observed. However, no correlation is obtained between the microcirculation with either the cutaneous temperature or the redness. These results indicate the transport of the drug in the blood from the upper to the deeper capillaries. Cutaneous temperature and redness are unsuitable parameters to measure the kinetics of the blood flow after topical application of drugs.

Administration, Topical↗

In vivo confocal scanning laser microscopy: comparison of the reflectance and fluorescence mode by imaging human skin.

Optical, noninvasive methods have become efficient in vivo tools in dermatological diagnosis and research. From these promising imaging techniques, only the confocal scanning laser microscopy (CSLM) provides visualization of subsurface skin structures with resolutions similar to those of light microscopy. Skin annexes, as well as cutaneous cells from different epidermal layers, can be distinguished excellently. Currently, two forms of application have been established in dermatological practice: the reflectance mode, predominantly in the clinical field, and the fluorescence mode in dermatological research. Differences in both methods exist in the preparative protocol, in maximum imaging depth and, particularly, in the gain of contrast extraction. The reflectance mode demonstrates naturally occurring tissue components, whereas the fluorescent CSLM achieves contrast by administering fluorescence dye, representing the dynamic distribution pattern of the dye's fluorescent emission. Therefore, the reflectance and fluorescent modes highlight various skin microstructures, providing dissimilar in vivo confocal images of the skin. This permits different predications and information on the state of the tissue. We report the advantages and disadvantages of both optical imaging modes. The comparison was drawn by scanning human skin in vivo. Representative images in varying depths were obtained and analyzed; preparation procedures are shown and discussed.

Humans↗