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Thomas Ruzicka

Publications and source records attributed to Thomas Ruzicka.

At least 73 records · Page 4Linked to original sources
PubMed2003

Linear arrangement of multiple deep penetrating nevi: report of first case and review of literature.

BACKGROUND: Deep penetrating nevus is a recently described variant of melanocytic nevi with clinical and histopathological features that may be confused with malignant melanoma, blue nevus, pigmented Spitz nevus, or congenital melanocytic nevus. We report a case with linear arrangement of multiple deep penetrating nevi. To our knowledge, such presentation has never been reported in the literature. OBSERVATIONS: We describe a patient with multiple darkly pigmented lesions in the right periauricular area, above and behind the ear. The histopathological features of these lesions were consistent with deep penetrating nevus. CONCLUSIONS: To our knowledge, this is the first report of linear arrangement of multiple deep penetrating nevi. We consider this case a unique presentation of deep penetrating nevus.

Adult↗
PubMed2003

Arginase 1 overexpression in psoriasis: limitation of inducible nitric oxide synthase activity as a molecular mechanism for keratinocyte hyperproliferation.

Abnormal proliferation of keratinocytes in the skin appears crucial to the pathogenesis of psoriasis, but the underlying mechanisms remain unknown. Nitric oxide (NO), released from keratinocytes at high concentrations, is considered a key inhibitor of cellular proliferation and inducer of differentiation in vitro. Although high-output NO synthesis is suggested by the expression of inducible NO synthase (iNOS) mRNA and protein in psoriasis lesions, the pronounced hyperproliferation of psoriatic keratinocytes may indicate that iNOS activity is too low to effectively deliver anti-proliferative NO concentrations. Here we show that arginase 1 (ARG1), which substantially participates in the regulation of iNOS activity by competing for the common substrate L-arginine, is highly overexpressed in the hyperproliferative psoriatic epidermis and is co-expressed with iNOS. Expression of L-arginine transporter molecules is found to be normal. Treatment of primary cultured keratinocytes with Th1-cytokines, as present in a psoriatic environment, leads to de novo expression of iNOS but concomitantly a significant down-regulation of ARG1. Persistent ARG1 overexpression in psoriasis lesions, therefore, may represent a disease-associated deviation from normal expression patterns. Furthermore, the culturing of activated keratinocytes in the presence of an ARG inhibitor results in a twofold increase in nitrite accumulation providing evidence for an L-arginine substrate competition in human keratinocytes. High-output NO synthesis is indeed associated with a significant decrease in cellular proliferation as shown by down-regulation of Ki67 expression in cultured keratinocytes but also in short-term organ cultures of normal human skin. In summary, our data demonstrate for the first time a link between a human inflammatory skin disease, limited iNOS activity, and ARG1 overexpression. This link may have substantial implications for the pathophysiology of psoriasis and the development of new treatment strategies.

Amino Acid Transport Systems, Basic↗
PubMed2003

Lyme borreliosis.

Lyme borreliosis is a multi-organ infection caused by spirochetes of the Borrelia burgdorferi sensu lato group with its species B burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii, which are transmitted by ticks of the species Ixodes. Laboratory testing of Lyme borreliosis includes culture, antibody detection using ELISA with whole extracts or recombinant chimeric borrelia proteins, immunoblot, and PCR with different levels of sensitivity and specificity for each test. Common skin manifestations of Lyme borreliosis include erythema migrans, lymphocytoma, and acrodermatitis chronica atrophicans. The last two conditions are usually caused by B garinii and B afzelii, respectively, which are seen more frequently in Europe than in America. Late extracutaneous manifestations of Lyme borreliosis are characterised by carditis, neuroborreliosis, and arthritis. We present evidence-based treatment recommendations for Lyme borreliosis and review the prevention of Lyme borreliosis, including the Lyme vaccines.

Adolescent↗
PubMed2003

Frequency of microsatellite instability in unselected sebaceous gland neoplasias and hyperplasias.

Sebaceous gland neoplasias are the cutaneous manifestation of the Muir-Torre syndrome, which is known to be a phenotypical variant of hereditary nonpolyposis colorectal cancer. Both hereditary nonpolyposis colorectal cancer and Muir-Torre syndrome are caused by inherited DNA mismatch repair defects. As a prominent molecular genetic feature, all tumors associated with a DNA mismatch repair defect exhibit high microsatellite instability. So far, the frequency of DNA mismatch repair defects in patients selected solely on the basis of a sebaceous gland tumor has never been determined. In order to estimate this frequency, we assessed microsatellite instability with up to 10 microsatellite markers in a newly collected unselected series of 25 sebaceous gland neoplasias (six sebaceous adenomas, 16 sebaceous epitheliomas, three sebaceous carcinomas) in comparison to 32 sebaceous gland hyperplasias from unrelated patients. As many as 15 of the 25 sebaceous gland neoplasias (60%), but only one of the 32 sebaceous gland hyperplasias (3%), exhibited high microsatellite instability. Thus, in our study, the majority of patients with a sebaceous gland neoplasia in contrast to patients with a sebaceous gland hyperplasia are highly suspicious for an inherited DNA mismatch repair defect. On the basis of the subsequently collected tumor histories, nine of the 15 patients with a high microsatellite unstable sebaceous gland neoplasia were identified to have Muir-Torre syndrome. In none of these cases, however, were the clinical Amsterdam criteria for diagnosing hereditary nonpolyposis colorectal cancer fulfilled. In the sebaceous tumors of the remaining six patients, high microsatellite instability was an incidental finding. In two of these six patients, single relatives were known to be affected with internal cancer; however, their family histories were not suggestive of Muir-Torre syndrome or hereditary nonpolyposis colorectal cancer. In comparison with microsatellite instability screening studies in a variety of other randomly selected tumors, our study identifies sebaceous gland neoplasias as tumors with the highest frequency of high microsatellite instability reported so far, whereas sebaceous gland hyperplasia rarely exhibits high microsatellite instability. Therefore, screening for microsatellite instability in sebaceous gland neoplasias will be of great value in the detection of an inherited DNA mismatch repair defect, which predisposes to various types of internal cancers.

Adult↗
PubMed2003

HAX-1, identified by differential display reverse transcription polymerase chain reaction, is overexpressed in lesional psoriasis.

Psoriasis is a chronic inflammatory disease characterized by epidermal hyperplasia and an inflammatory infiltrate. The normal differentiation from basal to granular keratinocytes with subsequent apoptosis and cornification is disturbed in the akanthotic epidermis. This could be due to both an excess of mitogenic stimuli with hyperproliferation and/or resistance to apoptosis. By mRNA differential display we found HAX-1 to be overexpressed in lesional psoriatic skin. The overexpression of HAX-1 was verified at the mRNA level by Northern blot and in situ hybridization, as well as at the protein level by Western blot and immunohistochemistry. Detection of HAX-1 in mRNA from different tissues showed strong expression in the brain, pancreas, skeletal muscle, and heart. In contrast to primary keratinocytes and melanocytes we found HAX-1 highly expressed in human immortalized keratinocytes (HaCaT) and different melanoma cell lines. In HaCaT cells as a model for psoriatic keratinocytes we found an increased ultraviolet-induced apoptosis after expression of HAX-1 antisense mRNA. In psoriasis, the epidermal differentiation could be disturbed due to the increased expression of HAX-1 and hence a prolonged resistance to terminal differentiation. Antiapoptotic mechanisms are an emerging concept for the understanding of the pathogenesis of this disease possibly leading to clinical applications.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Complementary therapy for atopic eczema and other allergic skin diseases.

Atopic eczema is one of the most common chronic inflammatory skin diseases, with a prevalence of at least 10% in children and 0.5-1% in adults. The disease shows a drastically increasing tendency. This article provides an overview of the pathophysiology, pathomechanisms, prevention, and treatment of atopic eczema. We present a therapeutic concept that integrates all aspects of the complex pathophysiology that is a prerequisite for individualized and successful treatment. This is based on intervention in the pathophysiology of atopic eczema and elimination of exogenous provocation factors. Particular attention is given to unconventional therapy options such as phytotherapy, which are attracting patients in many countries, and possible effects, side effects, and interactions with other drugs are discussed.

Adjuvants, Immunologic↗
PubMed2003

Treatment of cutaneous leishmaniasis by photodynamic therapy.

BACKGROUND: Cutaneous leishmaniasis represents a common health problem and standard treatments are often ineffective or yield poor cosmetic results. OBJECTIVE: We compared the efficacy of photodynamic therapy (PDT) with paromomycin sulfate in 10 lesions of cutaneous leishmaniasis. METHODS: Five lesions were treated by PDT with Metvix (Photocure, Oslo, Norway) and 75 J/cm(2) red light. PDT was performed twice weekly and, after 12 weeks, once weekly. The other 5 lesions were treated with paromomycin sulfate once daily. All nonresponding lesions of the paromomycin-treated plaques finally also underwent PDT. RESULTS: All 5 lesions treated by PDT and 2 of the paromomycin sulfate-treated plaques were clinically and histologically Leishmania free. Three lesions with poor response to paromomycin sulfate finally responded to subsequent PDT. Ten months after therapy there was no recurrence, and cosmetic outcome after PDT was excellent. CONCLUSION: PDT may be an effective therapeutic alternative in cutaneous leishmaniasis.

Adult↗
PubMed2003

Histopathologic findings in lupus erythematosus tumidus: review of 80 patients.

BACKGROUND: In a recent study, we demonstrated that lupus erythematosus (LE) tumidus (LET) is a distinct subset of cutaneous LE (CLE), which is clinically characterized by erythematous, urticaria-like, nonscarring plaques in sun-exposed areas. OBJECTIVE: Our purpose was to analyze skin biopsy specimens from 80 patients with this disease and to determine whether it could be differentiated from other variants of CLE on histopathologic grounds. METHODS: Skin biopsy specimens from 53 primary and 38 UVA- and/or UVB-induced lesions of 80 patients with LET were examined and compared with skin biopsy specimens from patients with discoid LE (DLE) and subacute CLE (SCLE). RESULTS: Specimens from LET lesions showed a characteristic and diagnostic pattern of perivascular and periadnexal cellular infiltrates in the papillary and reticular dermis composed almost entirely of lymphocytes. In some cases, few scattered neutrophils were present. Furthermore, interstitial mucin deposition was observed in all specimens, as confirmed by colloidal iron staining. In contrast to discoid LE and subacute CLE lesions, epidermal atrophy or alteration at the dermoepidermal junction was not detected. CONCLUSION: Skin lesions of patients with LET present with specific histopathologic features, and the differences compared with subacute CLE and discoid LE further support the concept to consider LET as a separate entity of CLE.

Dermis↗
PubMed2003

Tacrolimus ointment for the treatment of vulvar lichen sclerosus.

The treatment of vulvar lichen sclerosus is generally considered difficult. Ultrapotent corticosteroids represent the most effective topical treatment, but carry the risk of side effects such as skin atrophy. We describe a 71-year-old woman with long-standing vulvar lichen sclerosus refractory to conventional treatment. After 6 consecutive weeks of treatment with tacrolimus ointment 0.1% (Protopic) twice daily, signs and symptoms of lichen sclerosus resolved. To our knowledge, this is the first report of the use of topical tacrolimus, which does not induce skin atrophy, in the treatment of vulvar lichen sclerosus.

Aged↗
PubMed2003

Intolerance reactions due to the selective cyclooxygenase type II inhibitors rofecoxib and celecoxib. Results of oral provocation tests in patients with NSAID hypersensitivity.

Intolerance reactions due to the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) are frequent emergencies. It is thought that inhibition of the isoenzyme cyclooxygenase type I (COX-1) is responsible for the common NSAID-associated adverse effects, whereas inhibition of COX-2 is mainly responsible for the therapeutic effects. The goal of our study was to estimate the frequency of intolerance reactions due to ingestion of the two newly approved selective COX-2 inhibitors, rofecoxib or celecoxib. In a sample of 13 patients who had previously documented NSAID hypersensitivity reactions to non-selective COX inhibitors, 2 patients (15.3%) showed intolerance reactions (2 of 9 patients with rofecoxib, 1 of 5 patients with celecoxib). These drugs cannot therefore be administered uncritically to patients with known NSAID hypersensitivity. Selective COX-2 inhibitors can only be used as alternative drugs in these patients after assessing their specific tolerability in a properly performed provocation test.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Papulonodular mucinosis associated with subacute cutaneous lupus erythematosus.

Mucin deposition is a common histopathologic finding in lupus erythematosus (LE) but is rarely present in sufficient quantity to produce clinically apparent skin lesions. Until now, fewer than 40 cases of papulonodular mucinosis associated with LE have been reported in the literature, and it was associated with either systemic LE or discoid LE. For the first time, to our knowledge, we describe 2 patients with subacute cutaneous LE who presented with papulonodular mucinosis as a major clinical manifestation of their disease.

Adult↗
PubMed2003

Lupus erythematosus tumidus in childhood. Report of 3 patients.

Lupus erythematosus (LE) is a rare disorder in childhood. Most patients reported in the literature present with systemic manifestations, and, to date, fewer than 20 children with chronic cutaneous LE have been documented. In this article, we describe 3 patients with childhood LE tumidus, an uncommon but distinct subtype of chronic cutaneous LE. The lesions are characterized by erythematous, urticaria-like, nonscarring plaques in sun-exposed areas and, unlike in other variants of chronic cutaneous LE, there is no epidermal involvement. The clinical, photobiological, and histologic features as well as the differential diagnoses of childhood LE tumidus are discussed and compared with the adult form of this disease.

Child↗
PubMed2002

Molecular genetic analysis of malignant melanomas for aberrations of the WNT signaling pathway genes CTNNB1, APC, ICAT and BTRC.

Aberrant activation of the Wnt signaling pathway has been reported in different human tumor types, including malignant melanomas. We investigated 37 malignant melanomas (15 primary tumors and 22 metastases) for alterations of 4 genes encoding members of this pathway, i.e., CTNNB1 (beta-catenin gene, 3p22.1), APC (adenomatous polyposis coli gene, 5q22.2), BTRC (beta-transducin repeat-containing protein gene, 10q24.3) and ICAT (inhibitor of beta-catenin and Tcf-4, 1p36.2). Mutational analysis of CTNNB1 identified somatic mutations in 1 primary melanoma and 1 melanoma metastasis from 2 different patients (5%). Both mutations affected the N-terminal degradation box of beta-catenin, which is important for the regulation of beta-catenin homeostasis. Another primary melanoma carried a somatic APC missense mutation within the known mutation cluster region in exon 15. Fourteen tumors (40%) showed LOH at microsatellite markers on 1p36. None of the tumors had lost both copies of the ICAT gene, but 1 melanoma metastasis carried a somatic point mutation altering the translation start codon of ICAT. Real-time RT-PCR showed markedly reduced ICAT transcript levels (<or=20% relative to normal skin and benign melanocytic nevi) in 28/36 malignant melanomas (78%), including 13/14 tumors with LOH on 1p36. Allelic loss on 10q was detected in 15 tumors (44%). We found neither mutations nor complete loss of expression of the BTRC gene in our melanoma series. Taken together, our results indicate that the Wnt pathway may be altered in malignant melanomas by different mechanisms, including rare somatic mutations in CTNNB1, APC or ICAT, as well as low or absent expression of ICAT transcripts.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Characterization of the inflammatory infiltrate and expression of endothelial cell adhesion molecules in lupus erythematosus tumidus.

Lupus erythematosus tumidus (LET) is a disease with characteristic clinical and histopathologic features that has not always been considered a subset of cutaneous lupus erythematosus (CLE). Although LET was first mentioned in the literature in 1930, it has rarely been documented, and immunohistochemical studies have never been performed. The aim of the present study was to characterize the inflammatory infiltrate and to analyze the expression of endothelial cell adhesion molecules in skin specimens from patients with LET and to compare the results with those from patients with other variants of CLE, such as discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). Cryostat sections of lesional skin specimens from ten patients with LET demonstrated an infiltrate composed of more than 75% CD4+, CD8+, and HLA-DR+ cells. Interestingly, CD45RO+ cells, in contrast to CD45RA+ cells, were the prevailing inflammatory cell population. Compared with skin specimens from patients with DLE and SCLE, the mean expression of CD4+ and CD8+ cells was higher (but not significantly so) in LET, and no differences were observed with the other three antibodies. Furthermore, in contrast to controls, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, and P-selectin showed the same expression pattern in skin specimens from patients with DLE, SCLE, and LET. In conclusion, the inflammatory infiltrate of LET primarily consists of CD4+/CD8+ lymphocytes. Furthermore, expression of endothelial cell adhesion molecules was equally upregulated in LET compared with the expression in DLE and SCLE, suggesting a similar immunopathomechanism of these subtypes of CLE.

Amine Oxidase (Copper-Containing)↗
PubMed2002

Update on Kaposi's sarcoma and other HHV8 associated diseases. Part 1: epidemiology, environmental predispositions, clinical manifestations, and therapy.

Kaposi's sarcoma (KS) is a mesenchymal tumour involving blood and lymphatic vessels. Only recently has the pathogenesis of this extraordinary neoplasm been elucidated. Viral oncogenesis and cytokine-induced growth together with some state of immunocompromise represent important conditions for this tumour to develop. In 1994, a novel virus was discovered and termed human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpes virus, which can be found in all types of KS, whether related to HIV or not. In the era of highly active antiretroviral therapy (HAART), the incidence of AIDS-KS has considerably declined, probably due to enhanced immune reconstitution and anti-HHV8-specific immune responses. If HAART is able to prevent spreading of KS, local therapy of KS may become an essential component of patient management. Part 1 of the review covers the epidemiology, environmental predispositions, clinical manifestations, and therapy of KS. Newer treatments such as pegylated liposomal anthracyclines and experimental strategies are discussed. We also present rationales and graduated treatment algorithms for local and systemic therapy in patients with KS to appropriately meet the challenges of this extraordinary neoplasm. Part 2, to be published next month, will summarise recent insights in the pathogenesis of KS and will discuss other HHV8-related diseases such as Castleman's disease and primary effusion lymphoma.

AIDS-Related Opportunistic Infections↗