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Thomas Ruzicka

Publications and source records attributed to Thomas Ruzicka.

85 records · Page 5Linked to original sources
PubMed2002

Update on Kaposi's sarcoma and other HHV8 associated diseases. Part 2: pathogenesis, Castleman's disease, and pleural effusion lymphoma.

The pathogenesis of Kaposi's sarcoma (KS) is better understood since the identification of the novel human herpesvirus 8 (HHV8), which can be found in all forms of KS. Viral oncogenesis and cytokine-induced growth, as well as some states of immunocompromise, contribute to its development. Several virally encoded genes--eg, bcl-2, interleukin 6, cyclin D, G-protein-coupled receptor, and interferon regulatory factor--provide key functions on cellular proliferation and survival. Growth promotion of KS is further stimulated by various proinflammatory cytokines and growth factors such as tumour necrosis factor a, interleukin 6, basic fibroblast growth factor, and vascular endothelial growth factor, resulting in a hyperplastic polyclonal lesion with predominant spindle cells derived from lymphoid endothelia. HHV8 has recently been discovered to escape HLA-class-I-restricted antigen presentation to cytotoxic T lymphocytes by increasing endocytosis of MHC class I chains from the cell surface, thus enabling latent infection and immune escape in primary and chronic infection. Multicentric Castleman's disease is a rare lymphoproliferative disorder of the plasma cell type, which has been reported in both HIV-seropositive and HIV-seronegative patients, and which frequently contains HHV8 DNA. Pleural effusion lymphoma, or body-cavity-based lymphoma, belongs to the group of non-Hodgkin B-cell lymphomas characterised by pleural, pericardial, or peritoneal lymphomatous effusions in the absence of a solid tumour mass. Pleural effusion lymphoma has an intermediate immunophenotype lacking B or T lymphocyte antigens and also belongs to the diseases associated with HHV8.

Castleman Disease↗
PubMed2002

CCL27-CCR10 interactions regulate T cell-mediated skin inflammation.

The skin-associated chemokine CCL27 (also called CTACK, ALP and ESkine) and its receptor CCR10 (GPR-2) mediate chemotactic responses of skin-homing T cells in vitro. Here we report that most skin-infiltrating lymphocytes in patients suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10. Epidermal basal keratinocytes produced CCL27 protein that bound to extracellular matrix, mediated adhesion and was displayed on the surface of dermal endothelial cells. Tumor necrosis factor-alpha and interleukin-1beta induced CCL27 production whereas the glucocorticosteroid clobetasol propionate suppressed it. Circulating skin-homing CLA+ T cells, dermal microvascular endothelial cells and fibroblasts expressed CCR10 on their cell surface. In vivo, intracutaneous CCL27 injection attracted lymphocytes and, conversely, neutralization of CCL27-CCR10 interactions impaired lymphocyte recruitment to the skin leading to the suppression of allergen-induced skin inflammation. Together, these findings indicate that CCL27-CCR10 interactions have a pivotal role in T cell-mediated skin inflammation.

Animals↗
PubMed2002

Botulinum toxin A: successful décolleté rejuvenation.

BACKGROUND: Décolleté wrinkles develop with age. In women more than 35 years of age these wrinkles are still transient, but become permanent at about age 50. In a substantial number of women décolleté wrinkles, seem to be associated with an insertion of platysma exceeding the second intercostal space. We report botulinum A toxin therapy of these wrinkles in five patients. OBJECTIVE: To show the effect of botulinum A toxin on décolleté wrinkles. METHODS: All five women with décolleté lines treated with botulinum A had different varieties of the platysma muscle inserting deep down beneath the fourth intercostal space. During platysma contraction injection points were marked and a certain dosage of toxin was applied. RESULTS: Two weeks after therapy a significant improvement of the treated décolleté region was observed. CONCLUSION: These observations indicated that botulinum A toxin can be an effective and safe method in the temporary management of décolleté wrinkles. It should therefore be considered as a new adjuvant treatment in cosmetic décolleté rejuvenation.

Botulinum Toxins, Type A↗
PubMed2002

Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone acetate ointment in children with atopic dermatitis.

BACKGROUND: Vehicle-controlled studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of patients with atopic dermatitis (AD). OBJECTIVE: This study was undertaken to compare 0.03% and 0.1% tacrolimus ointment with 1% hydrocortisone acetate ointment in children 2 to 15 years of age with moderate-to-severe AD. METHODS: Treatment was twice daily to affected areas for 3 weeks in this multicenter, randomized, double-blind, parallel-group study. The primary endpoint was the modified eczema area and severity index (mEASI) mean area under the curve (mAUC) as a percentage of baseline. RESULTS: Five hundred sixty patients were randomized and received at least one application of ointment. Discontinuations included 21 of 189 patients from the 0.03% tacrolimus group, 13 of 186 patients from the 0.1% tacrolimus group, and 20 of 185 patients from the hydrocortisone acetate group. The median mEASI mAUC as a percentage of baseline showed 0.03% and 0.1% tacrolimus to be significantly more effective than 1% hydrocortisone acetate (P <.001) and 0.1% tacrolimus to be more effective than 0.03% tacrolimus (P =.006). The mEASI mAUC as a percentage of baseline was 44.8%, 39.8%, and 64.0% for patients who received 0.03% tacrolimus, 0.1% tacrolimus, and 1% hydrocortisone acetate, respectively. Transient skin burning was the only adverse event to show a higher incidence in the tacrolimus treatment groups than in the hydrocortisone acetate group (P <.05). Laboratory parameters showed no treatment differences and no marked changes over time. CONCLUSION: Tacrolimus, 0.03% and 0.1%, was significantly more effective than 1% hydrocortisone acetate and 0.1% tacrolimus was more effective than 0.03% tacrolimus in the treatment of moderate-to-severe AD in children. No safety concerns were identified.

Administration, Topical↗
PubMed2002

Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis.

BACKGROUND: Vehicle-controlled studies have demonstrated the efficacy and safety of tacrolimus ointment for patients with atopic dermatitis. OBJECTIVE: This study was undertaken to compare 0.03% and 0.1% tacrolimus ointment with 0.1% hydrocortisone-17-butyrate ointment, a midpotent to potent topical corticosteroid, in the treatment of adult patients with moderate-to-severe atopic dermatitis. METHODS: Patients applied ointment twice daily to all affected areas for 3 weeks in this multicenter, randomized, double-blind, parallel-group study. The primary endpoint was the modified eczema area and severity index (mEASI) mean area under the curve as a percentage of baseline. RESULTS: Five hundred seventy patients were randomized and received treatment. Discontinuations included 22 of 193 patients from the 0.03% tacrolimus group, 22 of 191 patients from the 0.1% tacrolimus group, and 17 of 186 patients from the hydrocortisone butyrate group. The median mEASI mean area under the curve as a percentage of baseline was 47.0%, 36.5%, and 36.1% for patients who received 0.03% tacrolimus, 0.1% tacrolimus, and 0.1% hydrocortisone butyrate, respectively. There was no statistically significant difference between 0.1% tacrolimus and 0.1% hydrocortisone butyrate; however, the lower improvement in mEASI for 0.03% tacrolimus was statistically significant when compared with 0.1% tacrolimus (P <.001) or hydrocortisone butyrate (P =.002). Skin burning and pruritus at the application site showed a higher incidence in the tacrolimus treatment groups than in the hydrocortisone butyrate group (P <.05). Laboratory parameters showed no treatment differences and no marked changes over time. CONCLUSIONS: The efficacy of 0.1% tacrolimus ointment was similar to that of 0.1% hydrocortisone butyrate ointment and was lower for 0.03% tacrolimus ointment. No serious safety concerns were identified.

Administration, Topical↗
PubMed2002

Methotrexate treatment for refractory subacute cutaneous lupus erythematosus.

Methotrexate is beneficial in rheumatoid arthritis and has been used in small studies of patients with systemic lupus erythematosus. We describe a patient with severe subacute cutaneous lupus erythematosus refractory to therapy with antimalarials and corticosteroids. Treatment with methotrexate resulted in complete clearing of the skin lesions without any side effects.

Adult↗
PubMed2002

Loss of DNA mismatch repair proteins in skin tumors from patients with Muir-Torre syndrome and MSH2 or MLH1 germline mutations: establishment of immunohistochemical analysis as a screening test.

Muir-Torre syndrome (MTS) is a rare autosomal-dominant disorder characterized by the predisposition to both sebaceous skin tumors (or multiple keratoacanthomas) and internal malignancies. A subtype of MTS is allelic to hereditary nonpolyposis colorectal cancer and is caused by germline mutations in the DNA mismatch repair genes MSH2 or MLH1. In these cases both internal and skin tumors show characteristic microsatellite instability (MSI). The aim of the present study was to determine whether immunohistochemical examination of MSH2 or MLH1 protein expression in MTS-associated skin tumors can be used as a diagnostic screening tool to identify patients with germline mutations in MSH2 or MLH1. In the present study 28 skin lesions from 17 patients (20 sebaceous gland tumors, 4 sebaceous hyperplasias, 3 keratoacanthomas, and 1 squamous cell carcinoma) were tested immunohistochemically with antibodies against MSH2 and MLH1. Eighteen of these tumors were from eight patients with known MSH2 germline mutations, two tumors were from a patient with a germline mutation in MLH1, and eight microsatellite stable sporadic skin tumors served as controls. One sample had to be excluded because of a lack of immunoreactivity. All eight microsatellite stable tumors expressed both DNA repair proteins. In 15 of the tumors from MSH2 germline mutation carriers, loss of MSH2 expression was observed, one tumor showed reduced MSH2 expression, and one tumor displayed positive immunoreactivity to MSH2. Both tumors of the MLH1 germline mutation carrier showed loss of the MLH1 protein. In conclusion, our findings demonstrate that immunohistochemical testing of MTS-related skin tumors is a reliable screening method with high predictive value for the diagnosis of the DNA mismatch repair-deficient MTS.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Metvix (PhotoCure).

Metvix is a photosensitive cream containing the methyl ester of 5-aminolevulinic acid, which has been developed and launched by PhotoCure in Sweden for the treatment of high-risk basal cell carcinoma and actinic keratosis.

Administration, Topical↗
PubMedDate not supplied

Potential future dermatological indications for tacrolimus ointment.

Tacrolimus ointment is a steroid-free topical immunomodulator developed for the treatment of atopic dermatitis, a common, chronic inflammatory skin disease. By inhibiting T-cell activation and cytokine production, topically applied tacrolimus modulates inflammatory responses in the skin. Numerous clinical trials have shown that it is effective and well tolerated for the treatment of atopic dermatitis, its licensed indication. In addition, numerous publications suggest that tacrolimus ointment may provide effective treatment for a variety of other inflammatory skin disorders, many of which are very difficult to manage with standard therapy. This paper reviews currently available evidence regarding the use of tacrolimus ointment in a range of dermatological disorders, including psoriasis, lichen planus, pyoderma gangrenosum, lichen sclerosus, contact dermatitis, leg ulcers in rheumatoid arthritis, steroid-induced rosacea and alopecia areata. It also provides recommendations for future clinical studies with tacrolimus ointment.

Adjuvants, Immunologic↗
PubMedDate not supplied

Recurrence rate of superficial basal cell carcinoma following successful treatment with imiquimod 5% cream: interim 2-year results from an ongoing 5-year follow-up study in Europe.

Imiquimod is an immune response modifier that acts through Toll-like receptor 7 to induce innate and cell-mediated immune responses. This ongoing phase III, open-label study conducted in Europe is evaluating the long-term (5 year) clinical efficacy and safety of imiquimod 5% cream applied once daily 5 times per week (5 x/week) for 6 weeks for the treatment of superficial basal cell carcinoma (sBCC). A total of 182 subjects were enrolled. The initial sBCC clearance rate was 90% (12-week post treatment), whereas the proportion of subjects who were clinically clear at 2 years (current time point) was estimated to be 79.4%. Local skin/application site reactions were the most frequently reported safety findings. Initial efficacy rates of imiquimod applied 5 x/week for 6 weeks demonstrate its clinical utility as an alternative approach to the treatment of sBCC. The recurrence rate seen to date supports ongoing follow up of subjects treated with imiquimod.

Adjuvants, Immunologic↗