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Biomedical subjects

U Mrowietz

Publications and source records attributed to U Mrowietz.

At least 55 records · Page 3Linked to original sources
PubMed1999

Comèl-Netherton syndrome complicated by papillomatous skin lesions containing human papillomaviruses 51 and 52 and plane warts containing human papillomavirus 16.

We describe a 28-year-old woman with characteristic clinical signs of Comèl-Netherton syndrome (CNS) who showed numerous plane warts on her face and forearms and papillomatous skin tumours affecting her groins and genitoanal skin. Using human papillomavirus (HPV) type-specific primers for cutaneous and mucosal HPV types we identified HPV 16-specific sequences in plane warts and HPV 51- and HPV 52-specific DNA in papillomatous skin from the patient's groins, suggesting a pathogenetic role (cofactor) for HPV in the development of verrucous skin lesions in patients with CNS. Whether the susceptibility to HPV infections is due to decreased cellular immunity or epidermal defence mechanisms remains to be seen.

Adult↗
PubMed1999

Treatment of severe psoriasis with fumaric acid esters: scientific background and guidelines for therapeutic use. The German Fumaric Acid Ester Consensus Conference.

Fumaric acid ester (FAE) therapy has proved to be safe and effective in patients with severe psoriasis vulgaris. This treatment was introduced nearly 30 years ago, but is only now gaining renewed interest among dermatologists. FAE therapy is licensed in Germany and registration is pending in many European countries. Multicentre trials have confirmed the beneficial effect of FAE in psoriasis and have defined the spectrum of its adverse effects. Although the mode of action of FAEs in the treatment of psoriasis is not fully understood, recent experimental data point towards a skewing of the Th1-dominated T-cell response in psoriasis to a Th2-like pattern, and inhibition of proliferation of keratinocytes. This article reviews the experimental and clinical information on FAEs in psoriasis and provides guidelines for the clinical use of FAEs derived from a consensus meeting of leading experts.

Cytokines↗
PubMed1999

Significant reduction of T-cell chemotaxis to MCP-1 in patients with primary and metastatic melanoma.

OBJECTIVE: To address whether circulating T-cells from the patients with primary and metastatic malignant melanoma show altered chemotaxis to monocyte-chemotactic protein 1 (MCP-1) and its relation to tumor infiltrating lymphocyte (TIL) and metastasis. METHODS: Chemotactic response of T-cells towards MCP-1 and immuno-histochemistry study of TIL and tumor-associated-macrophages (TAM) were investigated in patients with primary and metastatic melanoma compared to patients with basal cell carcinoma and healthy persons. RESULTS: T-cells from patients with primary and metastatic melanoma showed a significantly decreased chemotactic migration towards MCP-1 and T-cells from patients with basal cell carcinoma showed normal chemotactic response. Immuno-histochemistry study showed that there was no correlation between the number of TIL and the decreased chemotaxis of circulating T-cells to MCP-1 in patients with primary melanoma. CONCLUSIONS: Circulating T-cells from patients with primary and metastatic melanoma showed a MCP-1-specific decrease in chemotactic migration. This may be due to abnormal expression or modulation of MCP-1-receptor expression on these cells.

Adult↗
PubMed1998

Omega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, multicenter trial.

BACKGROUND: Profound changes in the metabolism of eicosanoids with increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Free eicosapentaenoic acid (EPA) may compete with liberated AA and result in an antiinflammatory effect. OBJECTIVE: Our purpose was to assess the efficacy and safety of intravenously administered fish-oil-derived lipid emulsion on chronic plaque-type psoriasis. METHODS: A double-blind, randomized, parallel group study was performed in eight European centers. Eighty-three patients hospitalized for chronic plaque-type psoriasis with a severity score of at least 15 according to the Psoriasis Area and Severity Index (PASI) participated in a 14-day trial. They were randomly allocated to receive daily infusions with either a omega-3 fatty acid-based lipid emulsion (Omegavenous; 200 ml/day with 4.2 gm of both EPA and docosahexaenoic acid (DHA); 43 patients) or a conventional omega-6-lipid emulsion (Lipovenous; EPA+DHA < 0.1 gm/100 ml; 40 patients). The groups were well matched with respect to demographic data and psoriasis-specific medical history. Efficacy of therapy was evaluated by changes in PASI, in an overall assessment of psoriasis by the investigator, and a self-assessment by the patient. In one center neutrophil 4- versus 5-series leukotriene (LT) generation and platelet 2- versus 3- thromboxane generation were investigated and plasma-free fatty acids were determined. RESULTS: The total PASI score decreased by 11.2 +/- 9.8 in the omega-3 group and by 7.5 +/- 8.8 in the omega-6 group (p = 0.048). In addition, the omega-3 group was superior to the omega-6 group with respect to change in severity of psoriasis per body area, change in overall erythema, overall scaling and overall infiltration, as well as change in overall assessment by the investigator and self-assessment by the patient. Response (defined as decrease in total PASI of at least 50% between admission and last value) was seen in 16 of 43 patients (37%) receiving the omega-3 emulsion and 9 of 40 patients (23%) receiving omega-6 fatty acid-based lipid emulsion. No serious side effects were observed. Within the first few days of omega-3 lipid administration, but not in the omega-6 supplemented patients, a manifold increase in plasma-free EPA concentration, neutrophil leukotriene B5 and platelet thromboxane B3 generation occurred. CONCLUSION: Intravenous omega-3-fatty acid administration is effective in the treatment of chronic plaque-type psoriasis. This effect may be related to changes in inflammatory eicosanoid generation.

Adult↗
PubMed1998

Treatment of psoriasis with fumaric acid esters: results of a prospective multicentre study. German Multicentre Study.

Systemic treatment of psoriasis with fumaric acid esters (FAE) has been found effective by empirical means. In recent years clinical studies have confirmed the antipsoriatic activity of a defined mixture of different FAE. The aim of the present prospective multicentre study was to investigate further the efficacy and safety of FAE therapy in a large number of patients with severe psoriasis vulgaris. From 101 patients included in the study 70 completed the treatment period of 4 months. Discontinuation was due to adverse events in seven, lack of efficacy in two, and other reasons, such as non-attendance for scheduled visits, in 22 patients. Evaluation of overall efficacy showed a decrease in psoriasis area and severity index of 80% after 4 months of FAE therapy. Laboratory investigations revealed a slight overall decrease of lymphocytes during the treatment period which was more than 50% below baseline in 10 patients. During weeks 4 and 8 mean eosinophil counts were above the normal range. At the end of FAE therapy elevated eosinophil counts had returned to normal values. None of the patients showed changes in renal function parameters throughout the study. Adverse events were reported in 69% of the patients mainly consisting of gastrointestinal complaints (56%) and flushing (31%). In five patients gastrointestinal complaints and in two patients flushing led to withdrawal from the study. Taken together the results of this multicentre study showed in a large number of patients that systemic FAE treatment is effective in severe psoriasis vulgaris. Transient eosinophilia seems to be a characteristic feature of FAE therapy, while lymphocytopenia is usually mild. Adverse effects are dose-related and consist mainly of gastrointestinal complaints and flushing.

Adult↗
PubMed1998

Hyperpigmentation due to topical calcipotriol and photochemotherapy in two psoriatic patients.

The vitamin D3 analogue calcipotriol (calcipotriene) is an effective topical treatment for psoriasis. In combination with other antipsoriatic agents, such as ultraviolet radiation, calcipotriol is reported to improve the overall efficacy of the treatment. Here we describe two patients treated with a combination treatment of calcipotriol and bath psoralens and ultraviolet A who developed hyperpigmentation at the lesional sites where calcipotriol ointment was applied.

Adult↗
PubMed1998

The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion.

Topical SDZ ASM 981 has been found to be highly effective in preclinical models of T-cell-mediated skin disease. T cell activation is crucial in the pathogenesis of psoriasis. It has been hypothesized that SDZ ASM 981 may prove to be an effective treatment for chronic plaque psoriasis. Therefore, the study objective was to determine the efficacy, tolerability and safety of the new topical macrolactam, SDZ ASM 981, for chronic plaque psoriasis. Ten patients with chronic plaque-type psoriasis were treated with SDZ ASM 981 (0.3% and 1.0%), the corresponding ointment base (placebo) and open-labelled clobetasol-17-propionate ointment (0.05%) in a randomized, double-blind, within-subject comparison for 2 weeks using the microplaque assay. Evaluation was performed by daily determination of clinical scores for erythema and induration. The results of the study showed that, after 2 weeks of treatment, total scores described by 92% for clobetasol, by 82% for 1 SDZ ASM 981, by 63% for 0.3% SDZ ASM 981 and by 18% for the ointment base (placebo). No adverse drug effects were seen in any patient throughout the study. We conclude from our results that the new macrolactam SDZ ASM 981 (1%) is similar to clobetasol-17-propionate (0.05%) in plaque-type psoriasis when applied topically under occlusion for 2 weeks using the microplaque assay.

Administration, Topical↗
PubMed1998

T-lymphocyte chemotaxis to IL-8 in patients with psoriasis in vitro.

OBJECTIVE: The critical role of infiltrating T cells in the pathogenesis of psoriasis is now well established. In order to determine whether circulating T cells from patients with psoriasis were also involved in the disease process, the authors investigated the biological behavior as studied by chemotactic activity of T cells in patients with psoriasis. METHODS: A 48 microchemotaxis chamber was employed to determine T-cell chemotaxis activity. In addition, the expression of T cell activation markers such as HLA-DR and interleukin 2 receptor were analysed with fluorescence activated cell sorting technique and serum IL-8 level was measured with ELISA methods. Forty-five patients with psoriasis (23 patients with severe psoriasis and 22 with mild psoriasis) and 21 patients with atopic dermatitis were investigated. For comparison, T-lymphocytes from 20 healthy controls were tested equally. RESULTS: T-cell chemotactic responses were significantly decreased in patients with severe psoriasis and atopic dermatitis as compared to healthy controls. Increased expression of activation markers such as HLA-DR and interleukin 2 receptor were demonstrated in circulating T cells from psoriatic patients and atopic dermatitis patients in comparison to healthy controls. Serum IL-8 level was significantly increased in patients with psoriasis and atopic dermatitis. CONCLUSIONS: Circulating T cells in patients with severe psoriasis show abnormal in vitro chemotactic response to IL-8. Furthermore, the in vivo activation state of T lymphocytes in these patients and increased level of serum IL-8 seemed to be associated to their decreased in vitro T-cell chemotactic responses.

Chemotaxis, Leukocyte↗
PubMed1997

[Toxic inner ear damage in topical treatment of psoriasis with salicylates].

BACKGROUND: Whereas cochlear impairment after intravenous ingestions of salicylates is well known, reports of cochlear symptoms after topical application are quite rare. The extent of the ototoxic salicylate impact is increased by diabetes, renal insufficiency, and alcoholism. PATIENT: This study presents a case report of a female patient who suffered a repeated, symmetric, pancochlear, reversible inner ear impairment after two treatments with salicylate containing ointment for psoriasis. The correlation of the salicylate therapy with the observed inner ear lesions is obvious due to the close interval between these incidences and to the audiologic criteria typical for salicylate intoxication. CONCLUSION: Audiologic controls should be carried out during extended local application of salicylate containing ointment.

Adult↗
PubMed1997

Phenotypic differences between human blood monocyte subpopulations in psoriasis and atopic dermatitis.

Peripheral blood monocytes seem to be of importance in the initiation and maintenance of cutaneous inflammatory disorders such as psoriasis and atopic dermatitis. Functional abnormalities of monocytes have been observed in both diseases. We sought to determine whether these abnormalities are reflected by an altered phenotypic expression of functionally active surface molecules. Peripheral blood monocyte subsets varying in cellular density and cell size from patients with psoriasis and atopic dermatitis were investigated using FACS analysis employing a panel of monoclonal antibodies (CD14, CD16, HLA-DR, HLA-DO, Fc epsilon RII, IL-2R, ICAM-1, CR3). Furthermore, the modulation of expression by interferon-gamma in monocyte subsets from patients was compared to normal controls. The results show that HLA-DR and -DQ expression on monocyte subsets in psoriatic patients was significantly decreased; "large" monocytes expressed significantly less HLA-DR than "small" monocyte subpopulations. Decreased HLA-DR and -DQ expression could be upregulated by incubation of psoriatic monocytes with IFN gamma. In atopic dermatitis, a different phenotype pattern of monocyte subsets was demonstrated: HLA-DR expression and HLA-DQ expression were both decreased in both "large" and "small" monocytes as compared to normal controls. However, there were no significant differences in HLA-DR and HLA-DQ expression between "large" and "small" monocyte subpopulations in atopic dermatitis. Moreover, the ICAM-1 and IL-2R expression of "large" and "small" monocyte subpopulations was significantly decreased in atopic patients from levels in normal controls and psoriatic patients. The altered expression of HLA-DR, -DQ ICAM-1 and IL-2R could be upregulated by incubation of atopic monocytes with IFN gamma. In addition, there was a significant increase in the percentage of monocytes in the differential count of patients with psoriasis or atopic dermatitis. We conclude that the differential phenotype pattern of surface molecules on monocytes in psoriasis and atopic dermatitis may reflect an abnormal monocyte maturation/differentiation state. This may explain the functional abnormalities of monocytes observed in patients with psoriasis and atopic dermatitis.

Adolescent↗
PubMed1997

Significant reduction of human monocyte chemotactic response to monocyte-chemotactic protein 1 in patients with primary and metastatic malignant melanoma.

The recruitment of leukocytes from the peripheral blood is a key event for the development and composition of the inflammatory infiltrate in solid tumors and tumor metastases like malignant melanoma. Tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) are thought to play a crucial rôle in tumor immunosurveillance. In malignant melanoma expression and secretion of monocyte-chemotactic protein 1 (MCP-1) have been demonstrated. MCP-1 serves as an attractant for monocytes and activated T-cells. In this study we addressed the question whether circulating monocytes show altered chemotaxis to MCP-1. Therefore the chemotactic responsiveness of monocytes towards MCP-1 was investigated in patients with primary and metastatic melanoma and compared to patients with basal cell carcinoma and healthy persons. The results show that monocytes from melanoma patients showed a significantly decreased chemotactic migration towards MCP-1 while chemotaxis to the stimulus N-formyl-methionyl-leucyl-phenylalanine (FMLP) remained normal. Patients with basal cell carcinoma showed normal monocyte chemotaxis to all stimuli tested. In primary melanoma, there was no relation of the number of TAM or TIL to the decreased chemotaxis of circulating monocytes to MCP-1. From these data it can be concluded that circulating monocytes from patients with primary and metastatic melanoma show a MCP-1-specific decrease in chemotactic migration. This may be due to deactivation or modulation of the MCP-1-receptor expression on these cells.

Adult↗
PubMed1997

The effect of tamol on human mast cell chymase and plasmin.

Tamol is widely used in the therapy of inflammatory dermatoses. It has pronounced astringent properties and is able to inactivate the neutrophil-derived elastase. Since plasminogen activation and release of mast cell chymase may occur in acute dermatitis, we investigated the inhibitory properties of tamol for these enzymes. Tamol proved to be a potent inhibitor of plasmin and mast cell chymase in concentrations relevant for use in dermatotherapy. The inhibition of mast cell chymase and plasmin by tamol was linear and non-competitive. The inactivation of proteolytic enzymes with the capacity to degrade extracellular-matrix proteins may be one of the major clinical effects of tamol in the treatment of acute inflammatory dermatoses.

Chymases↗
PubMed1997

Anthralin (dithranol) in vitro inhibits human monocytes to secrete IL-6, IL-8 and TNF-alpha, but not IL-1.

Anthralin is a most widely used compound for topical treatment of psoriasis. Whereas numerous studies have ascertained anthralin as a safe and effective drug its mode of action still remains unclear. Previous studies demonstrated dose-dependent inhibition of a number of pro-inflammatory functions in human neutrophils and monocytes (MO). The aim of the present study was to investigate in stimulated MO the effect of anthralin on the secretion of cytokines which are of known importance for the psoriatic tissue reaction. Highly purified MO were incubated with anthralin (0.01-1.0 microgram/ml), its clinically inactive derivative danthrone (0.1 and 10 micrograms/ml), the solvent acetone, or medium alone. Culture supernatants were analysed for immunoreactivity for interleukin-1 beta, and -8 (IL-1 beta, IL-8), and tumour necrosis factor alpha (TNF-alpha) by specific ELISA. IL-6 bioactivity was determined using the B9-bioassay. Additionally, IL-1 bioactivity was measured by the D10[N4]M-bioassay. The results show a dose-dependent inhibition of MO IL-6, IL-8, and TNF-alpha release with a half-maximal inhibitory concentration of 0.25-0.6 microgram/ml of anthralin. There was no effect of danthrone or acetone on the secretion of these cytokines from MO. Secretion of IL-1 beta immunoreactivity measured by ELISA as well as determination of biological activity of IL-1 using the D10[N4]M-bioassay revealed a slight increase in IL-1 secretion with a maximum at an anthralin concentration of 0.1 microgram/ml. Danthrone at a concentration of 10 micrograms/ml and acetone (0.1%) similarly enhanced IL-1 secretion from human MO measured by both methods. Our results demonstrate a differential, dose-dependent inhibition of cytokine secretion from human MO by anthralin. The present data provide evidence that the anti-inflammatory and anti-proliferative activity of anthralin may at least in part be due to its inhibitory effect on pro-inflammatory cytokine secretion by MO.

Administration, Topical↗
PubMed1996

[Rheumatoid neutrophilic dermatitis--a rare dermatosis in patients with active rheumatoid arthritis].

Rheumatoid neutrophilic dermatitis is a rare dermatologic disorder seen in patients with active rheumatoid arthritis. Clinically firm erythematous 3-5 mm papules are found mainly on the arms, the hips and the proximal thighs. The lesions may be pruritic leading to excoriations and crusts. Histology reveals a dense dermal infiltrate with neutrophilic granulocytes, while leukocytoclasia may be seen, vasculitits is not observed. This overview of rheumatoid neutrophilic dermatitis may help remind the practitioner to include this uncommon disorder in the differential diagnosis of rheumatoid arthritis-related dermatoses.

Arthritis, Rheumatoid↗