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Josef Smolle

Publications and source records attributed to Josef Smolle.

At least 37 records · Page 2Linked to original sources
PubMed2003

The plant lectin wheat germ agglutinin inhibits the binding of pemphigus foliaceus autoantibodies to desmoglein 1 in a majority of patients and prevents pathomechanisms of pemphigus foliaceus in vitro and in vivo.

Pemphigus foliaceus (PF) is a life-threatening autoimmune blistering skin disease caused by pathogenic IgG autoantibodies against desmoglein 1 (dg1), a desmosomal cadherin-type adhesion glycoprotein. Using lectins and glycosidases, we have shown that dg1 displays an N-glycosylation pattern of the complex triantennary type. We have found that lectins and glycosidases interfere with N-bound sugar residues on the amino-terminal ectodomain of dg1 and completely abolish, in vitro, the antigenicity of dg1 in most of the patients' sera. Moreover, in an ex vivo model using punch biopsies from normal human skin, we demonstrate that preincubation of the epidermis in wheat germ agglutinin (WGA) prevents PF autoantibody binding, acantholysis, and subcorneal blistering. In addition, we show that topical treatment with WGA inhibits PF autoantibody binding to keratinocytes in both newborn BALB/c mice and in organotypic human epidermis grafted onto the back of SCID mice. The epidermis of these pretreated animals displays a regular morphology, whereas control animals develop the immunopathologic phenotype of PF. These findings suggest that WGA may interfere with autoantibody binding to dg1, preventing experimental PF without affecting the adhesive function of dg1. Our observations may provide a new approach to the therapy of PF.

Administration, Topical↗
PubMed2003

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↗
PubMed2003

Diagnostic imaging of melanocytic skin tumors.

BACKGROUND: In tissue counter analysis, digital images are dissected into subregions (elements), and the digital information in each element is used for statistical analysis. The aim of this study was to test the applicability of tissue counter analysis and CART (Classification and Regression Tree) to the diagnostic discrimination of benign common nevi and malignant melanoma in dermatopathology. METHODS: Two hundred cases each of benign nevi and malignant melanoma were consecutively sampled. CART analyses of background versus tissue elements, cellular versus 'other' tissue elements and benign versus malignant cellular elements were performed. For diagnostic assessment, only the percentage of cellular elements suggestive for malignancy in each case was used. RESULTS: CART analysis led to a correct classification of 99% of background versus tissue elements, 96% of cellular versus 'other' tissue elements and 79.1% of benign versus malignant cellular elements. When the percentage of cellular elements suggestive for malignancy in each case was evaluated, 29.5 +/- 14% (range 4.1-62.4) 'malignant' elements were found in benign nevi (n = 200), in contrast to 75.9 +/- 13.9% (range 32.8-97.3) in melanoma (n = 200; z =-16.72, p < 0.001). It turned out that a threshold level of 52.51% provides a correct classification of 192 nevi and 186 melanoma out of 200 each (specificity 96%, sensitivity 93%, positive predictive value 95.9%). CONCLUSIONS: Tissue counter analysis combined with CART may be a useful method for diagnostic purposes in histopathology.

Decision Trees↗
PubMed2003

Penetration of piperacillin and tazobactam into pneumonic human lung tissue measured by in vivo microdialysis.

OBJECTIVES: The pharmacokinetic profile of antibiotics at the site of anti-infective action is one of the most important determinants of drug response, since it correlates with antimicrobial effect. Up to now, only limited information on the lung tissue pharmacokinetics of antibiotic agents has been available. The aim of this study was to measure, using a new microdialysis-based approach, antibiotic penetration into the extracellular space fluid of pneumonic human lung parenchyma. PATIENTS AND METHODS: The lung penetration of a combination of piperacillin and tazobactam, substances with low protein binding, was determined in five patients suffering from pneumonia and metapneumonic pleural empyema. The condition was treated by decortication after lateral thoracotomy. Intra-, or post-operatively, respectively, two microdialysis probes were inserted into pneumonic lung tissue, and into healthy skeletal muscle to obtain reference values. Serum and microdialysis samples were collected at 20-min intervals for at last 8 h following i.v. administration of a single dose of 4 g piperacillin and 500 mg tazobactam. RESULTS: The mean free interstitial concentration profiles of piperacillin in infected lung tissue and serum showed a maximal tissue concentration (Cmax) of 176.0 +/- 105.0 mg l-1 and 326.0 +/- 60.6 mg l-1, respectively. The mean AUC (area under the curve) for infected lung tissue was 288.0 +/- 167.0 mg.h l-1 and for serum 470.0 +/- 142.0 mg.h l-1. There was a statistically significant difference between AUC (lung) and AUC (serum) (P = 0.018) as well as between AUC (lung) and AUC (muscle) (P = 0.043). The intrapulmonary concentrations of piperacillin and tazobactam exceeded the minimum inhibitory concentrations (MIC) for most relevant bacteria for 4-6 h. The procedure was well tolerated by all patients and no adverse events or microdialysis-associated side-effects were observed. CONCLUSION: This microdialysis technique enabled continuous tissue pharmacokinetic measurement of free, unbound anti-infective agents in the lung tissue of patients with pneumonia. The present data corroborate the use of piperacillin and tazobactam in the treatment of lung infections caused by extracellular bacteria and demonstrate the distribution of piperacillin and tazobactam in the interstitial space of pneumonic lung tissue.

Adult↗
PubMed2003

Homeopathy in dermatology.

Alternative methods are commonly used in patients with dermatologic diseases, with homeopathy being one of the most common. Homeopathy was developed by Samuel Hahnemann (1755-1843) and is based on the law of similars and the law of infinitesimals. It is a regulatory therapy where high dilutions of particular compounds are thought to induce a counterreaction in the organism. In dermatology, homeopathy is often used in atopic dermatitis, other forms of eczema, psoriasis, and many other conditions. To date, however, there is no convincing evidence for a therapeutic effect. There are only a few controlled trials, most of them with negative results. The few studies with positive results have not been reproduced. Acceptance by the patient seems largely based on counseling and emotional care rather than on objective responses to the homeopathic drugs.

Evidence-Based Medicine↗
PubMed2003

Diagnostic tissue elements in melanocytic skin tumors in automated image analysis.

In tissue counter analysis, digital images are divided into subregions (elements), and the digital information in each element is used for statistical analysis. In this study, we assessed the morphologic details of tissue elements that have turned out to be of diagnostic significance in the discrimination of benign common nevi and malignant melanoma. After creation of a data set based on a total of 12,000 cellular elements obtained from 100 benign common nevi and 100 malignant melanomas, classification and regression tree (CART) analysis was performed to differentiate between cellular elements of nevi and melanoma. In a second step, the slides were re-evaluated by the decision tree; cellular elements suggestive either for benign common nevi or for malignant melanoma were highlighted on zoomed images of the whole sections, and the individual elements were displayed in galleries. Eight groups of elements (so-called terminal nodes) seemed to indicate benign common nevi, whereas seven terminal nodes were suggestive for malignant melanoma. The elements of nodes suggestive for benign nevi largely contained nevus cells with amphiphilic cytoplasm intermingled with fibrillary material, whereas the elements of the nodes suggestive for malignant lesions often showed hyperchromatism, perinuclear halos, heavy pigmentation, or a lymphohistiocytic infiltrate. Tissue counter analysis automatically detects tissue elements that are in accordance with morphologic criteria used in conventional histopathology for diagnostic discrimination.

Biopsy↗
PubMed2003

Tissue counter analysis of tissue components in skin biopsies: evaluation using CART (Classification and Regression Trees).

In tissue counter analysis, complex histologic sections are overlaid with regularly distributed measuring masks of equal size and shape, and the digital contents of each mask (or tissue element) are evaluated by gray level, color, and texture parameters. In this study, the feasibility of tissue counter analysis and classification and regression trees for the quantitative evaluation of skin biopsies was assessed. From 100 randomly selected skin biopsies, a learning set of tissue elements was created, differentiating between cellular elements, collagenous elements of the reticular dermis, fatty elements and other tissue components. Classification and regression trees based on the learning set were used to automatically classify tissue elements in samples of normal skin, benign common nevi, malignant melanoma, molluscum contagiosum, seborrheic keratosis, epidermoid cysts, basal cell carcinoma, and scleroderma. The procedure yielded reproducible assessments of the relative amounts of tissue components in various diagnostic groups. Furthermore, a reliable diagnostic separation of molluscum contagiosum versus normal skin and epidermal cysts, benign common nevi versus malignant melanoma, and seborrheic keratosis versus basal cell carcinoma was possible. Tissue counter analysis combined with classification and regression trees may be a suitable approach to the fully automated analysis of histologic sections of skin biopsies.

Biopsy↗
PubMed2003

Melanoma ex naevo: a study of the associated naevus.

It has been shown that the co-occurrence of melanoma and pre-existing naevus is not a random event and that acquired naevi may be precursors of melanoma. A critical area of chromosomal loss at 9p21 has been implicated in the genesis of malignant melanoma, representing a site of frequent somatic chromosomal deletions in melanoma. Allelic deletions within this chromosomal region most often include the tumour suppressor gene p16. The objective of this study was to search for allelic deletions on chromosome 9p21 in naevus cell clusters. A microdissection-based approach was used to analyse 30 archived primary cutaneous melanomas and associated naevi for loss of heterozygosity (LOH) at 9p21 using the polymorphic DNA markers D9S171 and IFNA. LOH was detected in 10 out of 27 informative naevi (37%) at D9S171 and in eight out of 19 (42%) at IFNA in the dissected naevus cell clusters, and in nine out of 27 (33%) at D9S171 and seven out of 19 (36%) at IFNA in the associated melanomas. In eight out of 46 (17%) cases, LOH was detected simultaneously in the naevus and the associated melanoma using both markers. Our results suggest a causal relationship for the development of melanoma within a pre-existent associated naevus. These data support the hypothesis that lesions within 9p21 play an important role in early melanoma development, since these genetic alterations are found in histologically benign melanoma-associated naevi.

Alleles↗
PubMed2003

Discrimination of benign common nevi from malignant melanoma lesions by use of features based on spectral properties of the wavelet transform.

OBJECTIVE: To evaluate the possibilities of describing and discriminating common nevi and malignant melanoma tissue with features based on spectral properties of the Daubechies 4 wavelet transform. STUDY DESIGN: Images of common nevi and malignant melanoma were dissected in square elements. The wavelet coefficients were calculated inside the square elements. The diagonal coefficients and related power spectra were used for further analysis. The analysis results served as guide for the selection of features, including standard deviations of wavelet coefficients inside the frequency bands and the energy of the frequency bands. These features describe properties of the frequency bands, representing information on different scales. To test the usefulness of the features for discrimination, a study set of 80 cases was classified by classification and regression trees analysis. The set was divided into a training set and a test set. RESULTS: In the case of benign common nevi, the energies of the lower frequency bands and higher, whereas malignant melanoma tissue shows more variability of the coefficients in higher-frequency bands. The influence on the detail properties of the images was studied by suppression of coefficients with low values, which are concentrated mainly in higher-frequency bands. In the case of benign common nevi the main information is contained in 15% of the coefficients and in the case of malignant melanoma, in 39%. The results of classification show a clear-cut difference between the cases. The classification correctly classified 95.78% of nevi elements and 94.22% of melanoma elements in the training set and 100% of cases of benign nevi and 80% of cases of malignant melanoma in the test set. CONCLUSION: Features based on the wavelet power spectrum contain sufficient information for differentiation between common nevi and malignant melanomas.

Artificial Intelligence↗
PubMed2002

Primary cutaneous lymphomas: applicability of current classification schemes (European Organization for Research and Treatment of Cancer, World Health Organization) based on clinicopathologic features observed in a large group of patients.

Classification of primary cutaneous lymphomas (PCLs) is the subject of ongoing controversy. Based on a series of 556 patients, the applicability of the European Organization for Research and Treatment of Cancer (EORTC) classification for PCLs was assessed and compared to the proposed World Health Organization (WHO) classification of hematologic malignancies. The large majority of patients could be properly classified according to the scheme proposed by the EORTC. Comparison of estimated 5-year survival for specific diagnostic categories of PCLs demonstrated nearly complete concordance of the present results with those of the EORTC study for most of the indolent cutaneous T-cell lymphomas and cutaneous B-cell lymphomas, whereas differences were found for mycosis fungoides-associated follicular mucinosis and Sezary syndrome. A few patients with newly described entities (CD8(+) epidermotropic cytotoxic T-cell lymphoma, primary cutaneous natural killer/T-cell lymphoma) could not be classified according to the EORTC scheme. Comparison of the EORTC with the WHO classification showed that the EORTC scheme allows a more precise categorization of the patients, especially for cutaneous B-cell lymphoma. In conclusion, the study confirmed that the EORTC classification allows a better management of patients with PCL. Small amendments to that classification should be carried out to account for recently described entities and to unify some of the diagnostic categories.

Adolescent↗
PubMed2002

Tissue counter analysis of histologic sections of melanoma: influence of mask size and shape, feature selection, statistical methods and tissue preparation.

BACKGROUND: Tissue counter analysis is an image analysis tool designed for the detection of structures in complex images at the macroscopic or microscopic scale. As a basic principle, small square or circular measuring masks are randomly placed across the image and image analysis parameters are obtained for each mask. Based on learning sets, statistical classification procedures are generated which facilitate an automated classification of new data sets. OBJECTIVE: To evaluate the influence of the size and shape of the measuring masks as well as the importance of feature selection, statistical procedures and technical preparation of slides on the performance of tissue counter analysis in microscopic images. As main quality measure of the final classification procedure, the percentage of elements that were correctly classified was used. STUDY DESIGN: HE-stained slides of 25 primary cutaneous melanomas were evaluated by tissue counter analysis for the recognition of melanoma elements (section area occupied by tumour cells) in contrast to other tissue elements and background elements. Circular and square measuring masks, various subsets of image analysis features and classification and regression trees compared with linear discriminant analysis as statistical alternatives were used. The percentage of elements that were correctly classified by the various classification procedures was assessed. In order to evaluate the applicability to slides obtained from different laboratories, the best procedure was automatically applied in a test set of another 50 cases of primary melanoma derived from the same laboratory as the learning set and two test sets of 20 cases each derived from two different laboratories, and the measurements of melanoma area in these cases were compared with conventional assessment of vertical tumour thickness. RESULTS: Square measuring masks were slightly superior to circular masks, and larger masks (64 or 128 pixels in diameter) were superior to smaller masks (8 to 32 pixels in diameter). As far as the subsets of image analysis features were concerned, colour features were superior to densitometric and Haralick texture features. Statistical moments of the grey level distribution were of least significance. CART (classification and regression tree) analysis turned out to be superior to linear discriminant analysis. In the best setting, 95% of melanoma tissue elements were correctly recognized. Automated measurement of melanoma area in the independent test sets yielded a correlation of r=0.846 with vertical tumour thickness (p<0.001), similar to the relationship reported for manual measurements. The test sets obtained from different laboratories yielded comparable results. CONCLUSIONS: Large, square measuring masks, colour features and CART analysis provide a useful setting for the automated measurement of melanoma tissue in tissue counter analysis, which can also be used for slides derived from different laboratories.

Adult↗
PubMed2000

Computer recognition of skin structures using discriminant and cluster analysis.

BACKGROUND/AIMS: Automated image analysis of complex tissues is usually limited by the difficulty of recognizing special structures by computer. The aim of this study was to test the applicability of discriminant and cluster analysis to the interpretation of skin images. METHODS: Digital images from microscopic, dermatoscopic and clinical views of skin specimens were electronically dissected into elements of equal size and shape, and a set of grey level, colour and texture features was assessed for each element. Elements were classified interactively and submitted to discriminant analysis. Furthermore, hierarchical cluster analysis was used to enable the system to classify the tissue elements automatically, based on the available digital information. The classification results were relocated to the original image in order to evaluate the performance of the procedure. RESULTS: The system performs well in reproducibly detecting different skin structures in digital images. Discriminant analysis of interactively classified elements yielded a correct reclassification in 98 to 100% of tissue elements. Among the cluster analysis procedures, the conservative Ward method after removal of all highly correlated features produced the best results. The method turned out to be applicable irrespective of the image source used. CONCLUSIONS: Discriminant and cluster analysis may be helpful techniques for a user-independent, subjectively unbiased measurement system of skin structures.

Journal Article↗
PubMedDate not supplied

Dystrophic epidermolysis bullosa inversa with COL7A1 mutations and absence of GDA-J/F3 protein.

Epidermolysis bullosa dystrophica inversa (DEB-I) is a very rare disease characterized by autosomal recessive inheritance that causes blistering and erosions on the trunk and extremities occurring in early infancy with a predilection for flexural and mucosal areas thereafter. Ultrastructural findings show dermolytic blistering and absent or rudimentary anchoring fibrils as in generalized forms of dystrophic epidermolysis bullosa. Immunoreactivity for type VII collagen, however, is preserved. We present two patients with DEB-I with compound heterozygosity for the two different COL7A1 mutations, one of them (Arg2069Cys in exon 74) carried by the heterozygous mother, the other one (Lys142Arg in exon 3) carried by the heterozygous father, accompanied by absence of the associated anchoring fibrils protein GDA-J/F3.

Adolescent↗
PubMedDate not supplied

Itraconazole in the treatment of tinea capitis caused by Microsporum canis: experience in a large cohort.

Mycotic scalp infection caused by Microsporum canis is one of the more recalcitrant disorders, with increasing incidence during the last decade. We report our experience with administration of itraconazole in 163 children (86 girls, 77 boys) with M. canis tinea capitis. Fifty-five patients had previous treatment with terbinafine without success. In all children, the dosage of itraconazole was adjusted according to body weight, with 5 mg/kg/day given in a continuous regimen either as a capsule (116 patients) or an oral suspension (47 patients). In all children, there was both clinical and mycologic cure after a mean treatment period of 39 +/- 12 days (range 10-77 days). Eleven children (6.7%) had side effects: diarrhea in five children, cutaneous eruption in four, and abdominal pain in two. Itraconazole was effective and safe for the treatment of M. canis tinea capitis.

Administration, Oral↗
PubMedDate not supplied

Pseudolymphoma occurring in a tattoo.

Pseudolymphomas are reactive inflammatory disorders due to different causative agents. Only a few cases of pseudolymphomas resulting from a tattoo have been described in the literature. We describe a 34-year-old woman with a nodular infiltrate limited to the red areas of a tattoo which had been administered 6 years before. Topical treatment with steroids had not been successful. As a result of clinical, histopathological and immunohistochemical findings and genotyping (polyclonal proliferation) the diagnosis of pseudolymphoma was made and total excision of the lesion was performed.

Adult↗