PubMed Health⌕ Search

Biomedical subjects

R Strohal

Publications and source records attributed to R Strohal.

At least 19 recordsLinked to original sources
PubMed2006

Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disorder that has a significant impact on quality of life and, particularly in moderate to severe cases, adversely affects the patient's overall health and well-being. Biological treatments, such as etanercept, are being widely adopted across Europe for treatment of moderate to severe psoriasis due to favourable safety and efficacy profiles. The increase in usage, combined with a growing body of clinical evidence, has identified a need to clarify the best use of etanercept within its current treatment label. OBJECTIVE: To prepare a series of recommendations agreed by an expert group of dermatologists, relating to the most effective use of etanercept for psoriasis in Europe, within the product license. METHODS: An expert panel of dermatologists from across Europe completed a Delphi survey to address the current use of etanercept in psoriasis in Europe. In June 2005 the results were presented to the expert panel at their nominal group meeting, and a consensus was agreed. RESULTS: It was recommended that, where possible, patients are initiated on the 50 mg twice-weekly (BIW) dose. Etanercept should be given until remission is achieved (maximum 24 weeks) and retreatment should be initiated according to the physician's judgement. Before commencing treatment, contraindications, such as infection or previous malignancy (within 5 years), should be ruled out. CONCLUSIONS: The consensus presented herein provides valuable clarification of use of etanercept according to the label, which may have wider implications relating to the use of all biological therapies in psoriasis.

Adolescent↗
PubMed2005

Nanocrystalline silver dressings as an efficient anti-MRSA barrier: a new solution to an increasing problem.

The emergence of multi-drug-resistant strains of bacteria represents a particular challenge in the field of wound management. The aim of the current study was to investigate whether nanocrystalline silver dressings possess the physical properties to act as a barrier to the transmission of methicillin-resistant Staphylococcus aureus (MRSA) in the laboratory setting and in a clinical setting. Initially, MRSA suspension and colony culture experiments were performed showing that nanocrystalline silver dressings act as potent and sustained antimicrobial agents, efficiently inhibiting MRSA penetration. Subsequently, a double-centre clinical trial was initiated using nanocrystalline silver dressings as a cover for 10 MRSA colonized wounds in a total of seven patients. By delineating the MRSA load on the upper side of the dressing and the wound bed each time the dressing was changed (i.e. after 1, 24, 48 and 72 h), nanocrystalline silver dressings were found to provide a complete, or almost complete, barrier to the penetration/spread of MRSA in 95% of readings. In addition, 67% of all wound observations showed a decrease in the MRSA load with an eradication rate of 11%. We believe that nanocrystalline silver dressings may become an important part of local MRSA management, with cost benefits to both patients and the healthcare system.

Bandages↗
PubMed2001

MART-1/Melan-A and tyrosinase transcripts in peripheral blood of melanoma patients: PCR analyses and follow-up testing in relation to clinical stage and disease progression.

The use of tyrosinase-based polymerase chain reaction (PCR) tests for the detection of circulating tumour cells in the blood of melanoma patients has led to highly controversial results. We here report on the analysis of 120 blood samples from 76 stage I to IV melanoma patients using a new MART-1/Melan-A PCR system in conjunction with the tyrosinase-specific assay reported in the literature. While there were no positive results in localized disease (stages I and II), identification of specific PCR products in stage III melanoma patients was restricted to the MART-1/Melan-A tests, with positive results in 11% (two out of 19) of the blood specimens analysed. Stage IV melanoma patients presented with the highest incidence of detectable mRNA levels, with positive results for tyrosinase in 38% (12 out of 32) and for MART-1/Melan-A in 22% (seven out of 32). By delineating 64 follow-up specimens covering sampling periods of up to 33 weeks, stable mRNA expression profiles were identified in nearly 95%. Four patients, however, showed PCR changes towards positive MART-1/Melan-A expression that were linked to metastatic melanoma progression. Taken together, PCR tests for tyrosinase and MART-1/Melan-A seem to lack sufficient detection frequencies for the routine monitoring of melanoma disease. Regarding the link between MART-1/Melan-A seroconversion and the development of metastatic disease, further studies are needed to clarify the clinical value of this observation.

Adult↗
PubMed1998

Reactivation of Behçet's disease in the course of multicentric HHV8-positive Castleman's disease: long-term complete remission by a combined chemo/radiation and interferon-alpha therapy regimen.

We used a new combined chemo- (COP/ABVD), radiation and interferon-alpha (10 x 10(6) IU s.c. 3x per week/12 months) therapy regimen to treat severe multicentric Castleman's disease (CD) complicated by relapsing Behcet's disease (BD) manifestations. More than 16 years after diagnosis of CD the patient remains in very good clinical condition, with remission of all CD and BD manifestations 13 months after discontinuation of the interferon-alpha treatment. In addition, our clinicopathological, immunohistological and virological data suggest a pathogenetic link between CD and BD via activation of pre-existing BD-specific plasma cells due to CD-related HHV8-induced overexpression of interleukin-6.

Adult↗
PubMed1998

First comparative delineation of the T cell receptor repertoire in primary and multiple subsequent/coexisting metastatic melanoma sites.

At present, very little is known about the types and heterogeneity of T cell responses and immunodominant epitopes of melanoma-associated antigens at coexisting sites of primary melanoma and metastatic lesions. To address this issue, we compared the T cell receptor (TCR) gene usage, complementary-determining region 3 diversity, and melanoma-associated antigens expression patterns of primary and metastatic melanoma specimens from three patients with partially homologous HLA class-1 types. Results obtained showed an overall predominance of a very limited number of TCRV regions with AV13 and BV14 being most frequently overexpressed. Sequencing of the dominating TCR transcripts confirmed the restricted usage of certain TCR specificities and, in two of the three patients, identified several identical TCR clonotypes at more than one metastatic site. Nevertheless, we failed to detect TCR transcripts that were common to all tumor deposits in a given patient and, within the majority of coexisting metastases, tumor-infiltrating lymphocytes preferentially used individual site-specifically expanded TCR beta-chain VJ segment combinations. This occurrence of individual responses simultaneously executed at and influenced in their specificity by the different sites of tumor growth, has important implications for the type of strategies chosen in the development of efficacious vaccines for patients with metastatic melanoma.

Antibodies, Neoplasm↗
PubMed1994

T-cell receptor repertoire of lymphocytes infiltrating cutaneous melanoma is predominated by V alpha specificities present in T-cells of normal human skin.

Lymphocytes infiltrating solid tumors can be propagated in vitro with interleukin 2 and are then capable, as CD8+ cytotoxic T-cells, of specific lysis of autologous tumor targets in a class I-restricted manner. Since the specificity of these cells is determined by their T-cell receptor (TCR) configuration, the aim of this study was to delineate the TCR V alpha repertoire of tumor-infiltrating lymphocytes within 24 melanoma specimens and to compare these data with the TCR expression pattern of unaffected peritumoral and normal human skin. While lymphocytes within all skin specimens tested expressed a substantial, albeit limited, heterogeneity of V alpha specificities with an average number of 9.0 different V alpha gene segments, the V alpha repertoire within cutaneous melanoma lesions was significantly more restricted (mean of V alpha expression, 3.86; P < 0.001) with a predominance of only 3 V alpha families (V alpha 13, V alpha 15, and V alpha 16), all of which were also found to be expressed within normal skin. Collectively, the fact that the TCR V alpha repertoire in melanoma is skewed toward the predominance of only a few V alpha regions may be indicative of a limited number of melanoma-associated antigenic determinants being involved in the anti-tumor immune response.

Adult↗
PubMed1994

Immunohistological analysis of anti-melanoma host responses.

Various clinical and experimental observations point to the existence of an immunological host defense in cutaneous malignant melanoma. To identify the major effector mechanisms mediating the specific anti-tumor immune response, we examined 23 benign and neoplastic melanocytic lesions (3 nevi, 14 primary melanomas, and 3 cutaneous and 3 systemic metastases) by quantitative immunohistology, and correlated these results with the histopathological and clinical subtypes of malignant melanoma. Our analyses indicate that CD3+ T-cell receptor alpha/beta-expressing lymphocytes are the prevailing leukocyte subset in primary as well as secondary malignant melanoma. We further observed that in early lesions (< 0.75 mm) of superficial spreading melanoma the vast majority of tumor-infiltrating lymphocytes (TIL) belong to the CD4+ subset and frequently express CD45RA antigens. In more advanced tumors, the contribution of CD8+ TIL gradually increases, indicating that the quality of the anti-tumor immune response changes during the course of the disease. Finally, we found that a varying percentage of cutaneous TIL express the cutaneous leukocyte antigen which is defined by the monoclonal antibody HECA 452 and preferentially expressed by skin-seeking memory T cells. In contrast, extracutaneous melanoma metastases (liver, brain, ovary) were completely devoid of HECA 452-reactive lymphocytes. These findings suggest that lymphocytes infiltrating cutaneous melanomas belong to a memory/effector T-cell subset functionally associated with the skin.

Antibodies, Monoclonal↗
PubMed1993

Nonbullous pemphigoid: prodrome of bullous pemphigoid or a distinct pemphigoid variant?

We describe two patients with pruritic, mainly urticarial or eczematous lesions associated with peripheral blood eosinophilia. No vesicles or blisters developed in either patient throughout the course of the disease (29 and 38 months, respectively). To characterize the clinicopathologic features of these patients we performed histopathologic studies, direct and indirect immunofluorescence, immunoelectron microscopy (patient 2), and immunoprecipitation of both patients' serum. Histopathologic examination revealed a moderate eosinophilic infiltrate partly arranged along the basement membrane zone and focally invading the epidermis. Linear deposits of immunoglobulin and C3 along the dermoepidermal junction were localized within the lamina lucida and over the hemidesmosomal plaques. Immunoprecipitation revealed the presence of circulating autoantibodies against the 230 kd bullous pemphigoid antigen. These findings suggest that our patients had a distinct, nonbullous variant of the pemphigoid spectrum.

Aged↗
PubMed1993

In vivo cytokine expression in normal and perturbed murine skin--analysis by competitive quantitative polymerase chain reaction.

Although cells from both epidermis and dermis have been shown to produce a variety of soluble mediators in vitro, it is not clear whether this reflects the in vivo situation. To study in vivo cytokine expression, whole skin as well as dispase-separated epidermis and dermis from normal adult mice were prepared and snap-frozen immediately. RNA was then extracted and analyzed both by conventional and by competitive quantitative polymerase chain reaction. Molecular analysis showed that murine skin in vivo constitutively expresses several cytokine genes at moderate (e.g., interleukin-1 alpha) or low (e.g., interleukin-6 and granulocyte-macrophage colony-stimulating factor) abundance. A striking, rapid upregulation was observed for some of these cytokines in the process of tissue separation. Of interest, the epidermal and dermal compartments exhibited different induction patterns: interleukin-1 alpha, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha expression were detected preferentially in the epidermis, whereas upregulation of interleukin-6 was found to be most prominent in the dermis. This pattern of cytokine expression was also reflected in supernatants generated from the respective single-cell suspensions. Thus, this study determines the baseline in vivo cytokine expression in the skin and the occurrence of immediate, compartment-specific alterations on perturbation. These data should contribute to our understanding of both skin homeostasis and the host-defense mechanisms initiated following injury to this organ.

Amino Acid Sequence↗
PubMed1993

Palladium in dental alloys--the dermatologists' responsibility to warn?

Palladium is increasingly used in industry, but also in fine jewelry and in dentistry. Thus, palladium-silver alloys comprise a substantial part of the noble metal ceramic alloy sales in Western countries. The increased use of this metal seems, however, to be paralleled by a rise in the number of reports of palladium allergy. Recently a European study reported a sensitization rate of 2.8%. In Austria, where palladium has started to displace amalgam in dental fillings because of concerns about mercury toxicity, and gold due to price factors, we have found a sensitization rate of 8.3% in unselected eczema patients. Despite the current lack of clear clinical relevance of this finding, these numbers should motivate us to question this substance as "the alloy of the future".

Burning Mouth Syndrome↗
PubMed1992

Fetal skin: a site of dendritic epidermal T cell development.

Thy-1 Ag and CD3-associated TCR-gamma (V gamma 3)/delta (V delta 1) are coexpressed on virtually all dendritic epidermal T cells (DETC) in the adult mouse. In contrast, day 16 fetal mouse skin contains small numbers of CD45+/Thy-1+/CD3- but no CD3+ cells. To see whether the CD45+/Thy-1+/CD3- fetal skin cells can qualify as DETC precursors, we transplanted day 16 fetal skin of C57BL/6 (Thy-1.2) mice onto adult B6Pl-Thy-1a (Thy-1.1) animals. At certain time points after transplantation, grafts were analyzed for the presence of Thy-1 and CD3/TCR Ag. Examination of the grafts, 4 days after transplantation, revealed the presence of few donor-type Thy-1.2+/CD3- and some Thy-1.2+/CD3+ epidermal cells of either round or dendritic configuration. At 10 weeks after transplantation, essentially all CD45+/Thy-1.2+ epidermal cells were anti-TCR V gamma 3 and anti-CD3-reactive, displayed a uniformly dendritic configuration, and, thus, represent DETC. Our assumption that CD45+/Thy-1+/CD3- cells are the only lymphocytes within day 16 fetal skin gained additional support by the observations: 1) that unfractionated as well as anti-CD45 gated single cell suspensions prepared from day 16 fetal skin were consistently devoid of anti-CD3 epsilon and anti-TCR V gamma 3-reactive cells; and 2) that stimulation of these cell suspensions with either Con A plus IL-2 or IL-2 alone regularly resulted in the outgrowth of CD45+/Thy-1+/CD3-/TCR V gamma 3- cells, but never in the appearance of CD45+/Thy-1+/CD3+/TCR V gamma 3+ cells. Our additional finding that Con A plus IL-2- or IL-2-stimulated day 16 fetal skin cells and cell lines derived therefrom contain transcripts of some (CD3 gamma, TCR C beta, TCR C gamma 1, TCR C gamma 4) but not of other (CD3 delta, CD3 epsilon, TCR C alpha, TCR C delta) genes encoding the CD3/TCR complex suggests that Thy-1+/CD3- fetal murine skin cells are of T cell lineage. We therefore propose that the fetal skin microenvironment can provide the stimuli promoting growth and maturation of CD3/TCR V gamma 3/V delta 1-expressing DETC from their CD3- precursors.

Animals↗
PubMed1992

Demonstration of a CD3+ lymphocyte subset in the epidermis of athymic nude mice. Evidence for T cell receptor diversity.

The existence of CD3/TCR-bearing lymphocytes in athymic and thymectomized chimeric mice implies that T cell maturation can occur in the absence of a thymus. Considering the possibility that the epidermis may be one of the organs providing T cell educating stimuli, we attempted to characterize the Thy-1+ epidermal lymphocyte population of athymic mice. Immunohistologic studies of epidermal sheets revealed (1) that Thy-1+ epidermal cells of C57BL/6 nu/nu mice are CD5-, CD4-, and predominantly CD8-, and (2) that a minor subset of these cells displays anti-CD3 epsilon reactivity. Although these CD3+ epidermal cells could hardly be detected at 6 wk of age, they comprised approximately 2% of all Thy-1+ epidermal cells in 12-mo-old athymic mice. Most of these CD3+ cells expressed TCR-gamma/delta, but TCR-alpha/beta+ cells were also present. TCR-gamma/delta+ epidermal T cells of athymic mice preferentially expressed TCR V gamma 2, V gamma 4, and V gamma 5 specificities rather than TCR V gamma 3 as found on DETC of euthymic mice. Using mitogenic stimuli, we have succeeded in establishing cell lines and clones from BALB/c nu/nu and C57BL/6 nu/nu epidermis. Their marker profile corresponds to that seen on resident CD3+ epidermal cells, as well as on a very small subset of CD3+ splenic and lymph node lymphocytes of athymic mice. The ontogenetic relationship, if any, between the epidermal and lymphoid CD3+, CD5-, CD4-, CD8- cells, has yet to be clarified. Cell lines/clones representative of resident CD3+ epidermal cells of nu/nu mice should provide a useful tool in the elucidation of homing patterns and functional properties of extrathymically matured T cells.

Age Factors↗
PubMed1991

The role of fetal epithelial tissues in the maturation/differentiation of bone marrow-derived precursors into dendritic epidermal T cells (DETC) of the mouse.

Our attempts to clarify the contribution of the thymic vs. the cutaneous microenvironment in the maturation of dendritic epidermal T cell (DETC) precursors into DETC gave diverse results. In one series of experiments, we found that i.v. injection of fetal thymocytes (containing a TCR V gamma 3-expressing subpopulation), but not of adult thymocytes (containing no TCR V gamma 3+ cells) results in the appearance of CD3/TCR V gamma 3+ dendritic epidermal cells (=DETC). In other experiments, we have obtained evidence that transplantation of day 16 fetal skin onto a Thy-1-disparate recipient results in the appearance of donor-type DETC. Our further observation that the transplanted skin contains CD45+/Thy-1+/CD3- lymphocytes, but no mature T cells, therefore implies that fetal skin can provide stimuli promoting the expression of CD3/TCR genes in immature (CD3-) DETC precursors. It remains to be seen whether both or only one of these maturational pathways are (is) followed under physiological conditions.

Animals↗
PubMed1991

Localized vs generalized pyogenic granuloma. A clinicopathologic study.

We herein report the unusual case of a previously healthy young man who had spontaneous development of multiple lobular capillary hemangiomata disseminated over the integument. Based on the observation that the single lesions exhibited (immuno)pathologic and ultrastructural features similar, if not identical, to those of late-stage pyogenic granulomas, we propose to nosologically include our patient's eruption within the disease spectrum of pyogenic granuloma. As opposed to the occurrence of localized forms of pyogenic granuloma, the disseminated eruption seen in our patient and in other patients whose cases are reported in the literature cannot be ascribed to physical trauma. As some of these latter patients suffered from an underlying malignant neoplasm, it is tempting to speculate that both exogenous (eg, trauma) and endogenous (eg, tumor cells) factors can lead to the release of mediators promoting the development of these vascular neoplasms.

Adult↗