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Biomedical subjects

Wilhelm Stolz

Publications and source records attributed to Wilhelm Stolz.

At least 19 recordsLinked to original sources

Discrimination of melanocytic tumors by cDNA array hybridization of tissues prepared by laser pressure catapulting.

Gene expression profiling by cDNA array analysis in melanoma is hampered by the need for large amounts of RNA to prepare reliable probes for array hybridization. On the other hand, for ex vivo analysis of malignant cells from melanocytic tumors laser pressure catapulting is an essential prerequisite to obtain noncontaminated melanocytic preparations; however, laser pressure catapulting prepared material provides only nanogram amounts of RNA. In this study we present an approach to overcome these limitations by combining laser pressure catapulting and real-time polymerase chain reaction based SMART cDNA amplification technology. Reproducible and reliable hybridization patterns from about 500 laser pressure catapulting prepared cell equivalents from 22 cases of melanocytic tumors were generated using array analysis. Univariate analysis revealed significant differences of the expression pattern of melanocytic nevi, melanomas, and melanoma metastases. Multivariate analysis with four genes being the best univariate discriminative features (tyrosinase related protein 2, translation initiation factor 2 gamma, ubiquitine conjugating enzyme E2I and one expressed sequence tag) allowed clustering of nevi, melanomas, and melanoma metastases with an accuracy of 82%. Data validation was performed by additional quantitative reverse transcription-polymerase chain reaction (TaqMan-reverse transcription-polymerase chain reaction). Taken together, this study shows, that (1) array analysis is feasible on tumors with rather low cell numbers, and (2) differences in expression profiles allow discrimination between benign and malignant lesions. Expression patterns of marker genes defined in unequivocal histopathologic entities may improve the diagnostic and prognostic assessment of difficult melanocytic lesions, which is still the hardest problem in dermatopathology.

Biopsy↗

[Detection of lymph node metastases of malignant melanoma by palpation and ultrasound].

BACKGROUND AND PURPOSE: Early detection of metastases of malignant melanoma has therapeutic implications. The aim of this study was to evaluate palpation and ultrasound examination in the diagnostics of lymph node metastases in locally advanced melanoma. PATIENTS AND METHODS: 83 patients suffering from melanoma (Clark level IV or V) were examined for lymph node metastases by palpation and sonography. Findings were compared to histopathologic results after lymph node extirpation if available or the findings at the next follow-up visit. RESULTS: Lymph node metastases were confirmed histopathologically in 14 patients at the first study visit, in three others at the control visit. Sensitivity, specificity, positive and negative predictive values of palpation for the detection of metastases or suspicious nodes with increasing volume at follow-up in this population were 65%, 81%, 48%, and 89%, and of ultrasound 100%, 66%, 45%, and 100%, respectively. CONCLUSION: Sonography of lymph nodes should be included as a standard procedure in the detection of metastases of locally advanced malignant melanoma.

Adult↗

Automated epiluminescence microscopy--tissue counter analysis using CART and 1-NN in the diagnosis of Melanoma.

BACKGROUND/PURPOSE: In tissue counter analysis, digital images are overlayed with regularly distributed measuring masks (elements) of equal size and shape, and the digital contents (grey level, colour and texture parameters) of each element are used for statistical analysis. In this study we assessed the applicability of tissue counter analysis and machine learning algorithms on tumour segmentation and diagnostic discrimination of benign and malignant melanocytic skin lesions. METHODS: A total of 369 standardised dermatoscopic images (93 melanomas, 276 benign nevi) were evaluated. The Classification and Regression Tree (CART) analysis was performed in order to differentiate between melanocytic skin lesions and surrounding skin. Instance-based learning (1-NN) was tested for differentiating between benign and malignant tumour elements. For diagnostic assessment, only the percentage of elements suggestive for malignancy in each lesion was used. RESULTS: Evaluation of a total of 369 melanocytic skin lesions showed a suitable segmentation of the tumour portion in 97.6%. When instance-based learning was applied to an independent test set, a threshold value of 27.4% of elements suggestive for malignancy recognised 35 out of 35 melanomas and 100 out of 101 nevi (sensitivity 100%, specificity 99%, positive predictive value 97.2%, negative predictive value 100%). CONCLUSION: Tissue counter analysis combined with machine learning algorithms turned out to be a useful method for diagnostic purposes in epiluminescence microscopy.

Algorithms↗

Principles of dermatoscopy of pigmented skin lesions.

There has been a dramatic increase in the incidence of malignant melanoma in most parts of the world. Because the tumor thickness is the most important prognostic factor for the prognosis of the malignant melanoma, the early detection of thin melanomas is essential. Dermatoscopy allows the physician to discriminate between melanocytic and nonmelanocytic lesions with high diagnostic accuracy and to detect initial malignant melanomas. We review the principles of dermatoscopy and the differential diagnosis of pigmented skin lesions. Before using the ABCD rule of dermatoscopy to classify melanocytic lesions into benign, suspicious, or malignant, the distinction between melanocytic and nonmelanocytic lesions is necessary. An essential prerequisite for the usefulness of this technique is adequate training.

Dermatology↗

Dermoscopy of pigmented skin lesions: results of a consensus meeting via the Internet.

BACKGROUND: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. OBJECTIVE: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. METHODS: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. RESULTS: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53). CONCLUSION: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.

Algorithms↗

Discrimination between gene expression patterns in the invasive margin and the tumour core of malignant melanomas.

Genes that determine the invasive capacity of the invasive front of malignant melanomas (MM) have not yet been systematically investigated in vivo. Therefore, we combined laser pressure catapulting (LPC) microdissection with cDNA microarray technology (DermArray, Research Genetics, representing about 5700 genes) to systematically analyse differences in gene expression profiles between the invasive margin and the tumour centre in nine cases of vertical growth phase MM. Signal-to-noise statistical algorithms combined with hierarchical clustering were performed to determine class-separating genes. The gene encoding phosphoenolpyruvate carboxykinase 1 (PEPCK), the Homo sapiens gene similar to Saccharomyces cerevisiae SSM4 (TEB4), the gene encoding ribosomal protein L19, the Homo sapiens gene similar to the Aspergillus nidulans SudD (a suppressor of the bimD6 homologue), the gene encoding the interleukin-3 receptor alpha subunit, the gene encoding the inositol 1,4,5-triphosphate 3-kinase isoenzyme, and three anonymous expressed sequence tags were identified as class-separating genes. These genes significantly discriminate between the invasive front and the tumour centre. Using this set of genes, 15 out of 18 LPC-dissected MM regions could be grouped correctly. We conclude that the candidate genes identified could spark further research on MM progression and may provide novel prognostic parameters.

Algorithms↗

Treatment of Old World cutaneous leishmaniasis with intralesionally injected meglumine antimoniate using a Dermojet device.

Pentavalent antimonial compounds, the mainstay in the treatment of the various forms of leishmaniasis, have considerable toxicity, are difficult to administer and expensive. We describe a safe and efficient therapeutic modality using a spring-loaded and air-powered device for the intralesional injection of a high-velocity meglumine antimoniate microspray in a patient with cutaneous leishmaniasis.

Adolescent↗

Orofacial granulomatosis as the initial presentation of Crohn's disease in an adolescent.

Orofacial granulomatosis (OFG) is a rare and heterogeneous clinical condition that presents with chronic swelling of the oral or facial tissues due to granulomatous inflammation. It is histologically characterized by noncaseating giant cell granulomata and epithelioid histiocytes. OFG includes the previously recognized clinical entities of Melkersson-Rosenthal syndrome and cheilitis granulomatosa (Miescher's cheilitis). A consistently effective medical treatment is not currently available. We describe an adolescent patient with a history of recurrent orofacial swelling preceding gastrointestinal symptoms by several years. He exhibited clinical and histological changes consistent with the diagnosis of OFG. It was resistant to standard therapies such as topical corticosteroids. Thorough history taking and clinical examination suggested Crohn's disease (CD), and further tests confirmed the diagnosis. The patient improved promptly after initiating oral treatment for CD with mesalazine and prednisolone. We conclude that OFG may be under- or misdiagnosed since the clinical manifestation may be misleading and its course is independent of or even preceding CD. Thus, patients with OFG should be asked about gastrointestinal symptoms consistent with CD. Those with suspicious symptoms should undergo a careful gastrointestinal evaluation, possibly including enteroclysis and complete gastrointestinal endoscopic examination, especially when the patient's history is conspicuous.

Adolescent↗

Treatment of atopic dermatitis and impact on quality of life: a review with emphasis on topical non-corticosteroids.

Atopic dermatitis (AD) is a chronic skin disease with increasing prevalence and rising costs. Stigmatisation and pruritus are only some aspects of potential quality-of-life (QOL) impairments. AD is not curable and repeated treatments are often necessary. At present, treatment with topically-applied corticosteroids is state-of-the-art for mild to moderate flare-ups. However, many patients are worried about the use of corticosteroids due to the widespread fear of adverse effects. In this review the present literature is analysed concerning impact on quality of life for topically-applicable alternatives to the state-of-the-art treatment. For comparison reasons, data from other treatment modalities are additionally given. Characteristics of studies were analysed using 'general' (year and mode of publication, type and aim of study, number of patients, and clinical measurement) and 'QOL specific' criteria (type and number of QOL measurements including relevance for study aim and age group, validation in used language, sensitivity to change, and improvement at end of study). QOL data are published only in the minority of studies evaluating treatment efficacy and do not cover the variety of possible therapies. Data are available for tacrolimus, pimecrolimus, UVA/UVB combination and UVB narrowband (topical non-corticosteroidal treatments), as well as for topical corticosteroids, cyclosporin, and inpatient treatment. All studies provided a marked improvement in quality of life after therapy. One study assessed quality of life after a treatment-free follow-up period obtaining a clear increase in impact on quality of life. Since studies used different QOL measurements and vary in inclusion criteria, treatment schedules and presentation of results, a comparison of QOL improvement is not recommended. A single randomised study compared topically applied non-corticosteroidal treatment (UVA/UVB combination) with another treatment modality (cyclosporin) and found no difference in QOL improvement. At present, there is a clear lack of controlled randomised studies evaluating different active treatment modalities and their impact on quality of life. Consensus meetings are desirable to formulate guidelines for the selection and correct use of QOL measurements. Patients' fear of side effects (e.g. concerning corticosteroids) should be integrated in QOL questionnaires for evaluation of possible compliance problems and real costs. Since relapse after treatment is frequent in AD, QOL measurements should also be performed after a treatment-free follow-up period. At present, we can not answer the question 'which treatment best improves quality of life in AD?'.

Administration, Topical↗

IgE-mediated anaphylactic reaction induced by succinate ester of methylprednisolone.

BACKGROUND: In systemic administration the prevalence of anaphylactic reactions attributable to corticosteroids is approximately 0.3%. Positive prick tests with different corticosteroids have been reported suggesting an immunoglobulin (Ig)E-mediated mechanism. OBJECTIVE: A 42-year-old man with multiple sclerosis developed flush, erythema, and itching a few minutes after the begin of an intravenous infusion of methylprednisolone-21-sodium succinate. DIAGNOSTIC AND RESULTS: Prick tests were found to be positive with methylprednisolone-21-sodium succinate and prednisolone-21-sodium succinate, whereas prick tests with prednisolone without ester and betamethasone-21-dihydrogen phosphate showed negative results. Oral challenge with prednisolone without ester and intravenous challenge with betamethasone-21-dihydrogen phosphate were well tolerated. Specific IgE-antibodies against methylprednisolone-21-sodium succinate were found in the serum of the patient. Because of the positive prick test and specific IgE antibodies against methylprednisolone-21-sodium succinate, the diagnosis of IgE-mediated anaphylactic reaction could be proven. Succinate ester was suspected to be immunogenic, as other corticosteroids without this particular ester or with other substitutions at the C21 remained negative both in the prick and the challenge tests. CONCLUSIONS: This patient showed an adverse reaction caused by methylprednisolone-21-sodium succinate. The uniqueness in this case was the presence of specific IgE antibodies against this esterified corticosteroid in the patient's serum proving that this reaction was based upon a true IgE-mediated mechanism.

Adult↗

Benign Degos' disease developing during pregnancy and followed for 10 years.

Degos' disease, or malignant atrophic papulosis, is a rare and often fatal multisystem vasculopathy of unknown etiology. The cutaneous manifestations comprise erythematous papules, which heal to leave scars with a pathognomonic central porcelain-white atrophic area and a peripheral telangiectatic rim. Involvement of the gastrointestinal tract is observed in 50% of cases, with intestinal perforation being the most common cause of death. Other organ systems can also be affected; 20% of cases involve the central nervous system. Systemic manifestations usually develop from weeks to years after onset of skin lesions or, in rare instances, may precede skin lesions. In the patient with Degos' disease reported in this article, the characteristic skin lesions developed during pregnancy, a precipitating event not previously reported. She has survived an unusually long time (10 years) without visceral or neurological involvement, despite florid cutaneous lesions. Moreover, we could detect the presence of antiphospholipid antibodies, the significance of which are currently unclear. These observations therefore confirm that there may be a strictly cutaneous form of Degos' disease with a favourable prognosis.

Antibodies, Antiphospholipid↗

Eruptive multiple lentigo-maligna-like lesions in a patient undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing colorectal carcinoma: a lesson for the pathogenesis of malignant melanoma?

Induction of multiple eruptive dermal and atypical melanocytic naevi has frequently been reported in children with malignant haematological diseases and chemotherapy-induced immunosuppression. This is the first report of an adult patient to develop multiple eruptive melanocytic skin lesions while undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing cancer. Our observation adds further evidence to the link between systemic (iatrogenic or intrinsic) immunosuppression and the induction of melanocyte proliferation and transformation.

Administration, Oral↗

Multiple, bilateral and painful ear nodules of the anthelices: a variant of chondrodermatitis nodularis?

A case of a distinctive clinicopathologic condition of the ear cartilage is presented, characterized by multiple, bilateral and painful nodules of the anthelices without epidermal involvement. Histologically, there was a peri-chondrial lymphohistiocytic infiltrate and a small focus of degenerate, basophilic cartilage as well as cystic chondromalacia containing an amorphous mass. This condition is both clinically and histopathologically distinct from other causes of ear nodules, although the lesions seen in our patient exhibit features of chondrodermatitis nodularis helices and therefore could well be a variant of the latter.

Adult↗