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J Smolle

Publications and source records attributed to J Smolle.

At least 55 records · Page 3Linked to original sources
PubMed1998

Ultraviolet radiation of melanocytic nevi: a dermoscopic study.

BACKGROUND: UV radiation can lead to clinical, histological, and ultrastructural changes in melanocytic nevi. In this study, we investigated whether exposure to 2 minimal erythema doses of UV radiation induces changes in the dermoscopic image of acquired melanocytic nevi. OBSERVATIONS: Fifteen melanocytic nevi were exposed to 2 minimal erythema doses of UV radiation. Differences in dermoscopic parameters (asymmetry, border, erythema, and telangiectasias in the nevus; pigmentation; hypopigmented areas; presence, regularity, and sharpness of pigment network; and brown-black globules) in digital dermoscopic images taken before and 3, 7, 14, and 28 days after UV irradiation were scored. Three days after UV irradiation, the borders of nevi were more faded (P<.02), the nevi were darker brown (P<.02), the hypopigmented areas were smaller (P<.02), and the pigment network structures were more faded (P<.007) and less prominent (P<.02) than before UV irradiation. Seven days after UV irradiation, pigmented globules have also grown (P<.05). After 28 days, all parameters, except hypopigmented areas, were essentially the same as before UV irradiation. CONCLUSION: UV irradiation of melanocytic nevi with 2 minimal erythema doses induces transient changes in their dermoscopic appearance that are sometimes suggestive of malignant melanoma.

Adult↗
PubMed1998

Entry into afferent lymphatics and maturation in situ of migrating murine cutaneous dendritic cells.

An important property of dendritic cells (DC), which contributes crucially to their strong immunogenic function, is their capacity to migrate from sites of antigen capture to the draining lymphoid organs. Here we studied in detail the migratory pathway and the differentiation of DC during migration in a skin organ culture model and, for comparison, in the conventional contact hypersensitivity system. We report several observations on the capacity of cutaneous DC to migrate in mouse ear skin. (i) Upon application of contact allergens in vivo the density of Langerhans cells in epidermal sheets decreased, as determined by immunostaining for major histocompatibility complex class II, ADPase, F4/80, CD11b, CD32, NLDC-145/DEC-205, and the cytoskeleton protein vimentin. Evaluation was performed by computer assisted morphometry. (ii) Chemically related nonsensitizing or tolerizing compounds left the density of Langerhans cells unchanged. (iii) Immunohistochemical double-staining of dermal sheets from skin organ cultures for major histocompatibility complex class II and CD54 excluded blood vessels as a cutaneous pathway of DC migration. (iv) Electron microscopy of organ cultures revealed dermal accumulations of DC (including Birbeck granule containing Langerhans cells) within typical lymphatic vessels. (v) Populations of migrating DC in organ cultures upregulated markers of maturity (the antigen recognized by monoclonal antibody 2A1, CD86), but retained indicators of immaturity (invariant chain, residual antigen processing function). These data provide additional evidence that during both the induction of contact hypersensitivity and in skin organ culture, Langerhans cells physically leave the epidermis. Both Langerhans cells and dermal DC enter lymphatic vessels. DC mature while they migrate through the skin.

Animals↗
PubMed1998

Automated measurement of melanoma cross-sectional area.

The object of this study was to evaluate the prognostic impact of a cross-sectional area measured in routinely stained slides of cutaneous melanoma using fully automated image analysis. Hematoxylin-eosin stained slides of 238 specimens of primary cutaneous melanoma with Clark levels III to V were evaluated by digital image analysis using color video images, a scanning stage, and autofocus equipment. The cross-sectional area was significantly related to metastasis-free survival. Lesions with a cross-sectional area < or = 12 mm2 showed a 2-year metastasis-free survival rate of 92+/-2% compared with 41+/-8% in lesions with a cross-sectional area > 12 mm2 (log rank test: z = 71, p < 0.0001). The same was true for overall survival (98+/-1% compared with 82+/-6%; z = 42.12, p < 0.0001). In multivariate analysis, the cross-sectional area seems to provide prognostic information in addition to that provided by Breslow's index. In cases with regression and in small melanomas with vertical growth, however, metastatic spread may occur in lesions with a small cross-sectional area. It was concluded that automated measurement of the cross-sectional area may be helpful in assessing prognosis in cutaneous melanoma.

Adolescent↗
PubMed1998

Autocrine growth stimulation as a potential source of asymmetry in melanocytic skin tumors.

The presence of asymmetry is a major diagnostic criterion for the differentiation of melanoma from benign melanocytic proliferations. It is helpful in both clinical and histological evaluation. The underlying biological features that determine asymmetry have not yet been evaluated. Using computer simulation of the growth of neoplasms, we demonstrate that a functionally homogeneous cell population can give rise to asymmetric lesions when the cells respond to autocrine growth signals. In contrast, neoplastic cells that depend on paracrine stimuli tend to form symmetric lesions. Since the progression of melanocytic neoplasms has been demonstrated to be accompanied by increasing independence of paracrine growth signals and the development of autocrine loops, autocrine growth stimulation has to be considered as a potential source of asymmetry in melanoma.

Autocrine Communication↗
PubMed1998

Expression of two morphologic parameters concerning tumor-stroma interaction in benign and malignant melanocytic skin lesions.

The importance of tumor-stroma interaction in many solid tumors of the skin has been demonstrated in recent years. Invasion and metastasis require multiple interactions of the tumor cells with the surrounding stroma. In malignant melanoma most studies concerning tumor-stroma interaction focus on the peritumoral infiltrate, whereas other aspects of tumor-stroma interactions have not been considered. We investigated two morphologic criteria of tumor-stroma interaction in melanocytic skin tumors. Simple infiltration into the surrounding dermis or subcutis without evident stromal reaction (DERMSIMPLE) and the existence of morphologically intact collagen bundles of the reticular dermis within the tumor bulk (PRECOLL) were examined in 373 benign common nevi, 239 dysplastic nevi, 322 Spitz nevi, 368 primary malignant melanomas, and 344 melanoma lesions metastatic to the skin. Our results showed that there is a highly significant difference in the expression of DERMSIMPLE and PRECOLL between benign and malignant melanocytic skin tumors. Concerning DERMSIMPLE, 13.3% of benign skin lesions compared with 28.2% of malignant lesions were positive for this feature; PRECOLL was found in 13.8% benign and 37.1% malignant lesions (chi-squared test; p = 0.0001 for both features). Furthermore, it could be demonstrated that simple infiltration into the surrounding stroma as well as the existence of morphologically intact collagen bundles of the reticular dermis within the tumor bulk increases with tumor progression; between primary malignant melanoma and melanoma metastatic to the skin, for example, there was a highly significant difference for DERMSIMPLE, as well as for PRECOLL (chi-squared test; p = 0.00001). These data indicate that morphologic aspects of tumor-stroma interactions in different benign and malignant melanocytic skin lesions may reflect biological behavior of tumor cells. The analysis of further aspects of tumor-stroma interaction and the relation to the patient's outcome may lead to the development of further prognostic parameters in malignant melanoma.

Collagen↗
PubMed1998

Incorporation of pre-existing collagen bundles in primary cutaneous melanoma.

In a previous qualitative study it has been shown that the incorporation of pre-existing collagen bundles from the reticular dermis into the bulk of melanoma lesions metastatic to the skin indicates rapid systemic spread. In the present study the amount of pre-existing dermal collagen in the bulk of the melanoma lesions in 267 cases of primary melanoma of the skin with a Clark level of at least III was quantitatively assessed using automated image analysis based on RGB (red, green and blue) colour images of sections stained with haematoxylin and eosin. There was a weak correlation between the amount of pre-existing collagen and the Clark level and the Breslow index. With regard to prognosis, a large amount of pre-existing collagen (> 0.13 mm2 per index slide) was significantly associated with a particularly poor outcome (24-month survival rate: 71 +/- 17% compared with 96 +/- 2%; log rank test: P < 0.001). It is clear that a large amount of pre-existing collagen bundles occurring as a particular feature of tumour-stroma interaction indicates high metastatic capacity in primary malignant melanoma.

Adolescent↗
PubMed1998

Sensitivity in the clinical diagnosis of malignant melanoma.

Accurate clinical diagnosis of malignant melanoma is of great importance for early detection and further treatment. The purpose of this retrospective study was to evaluate the accuracy of clinical diagnosis by using different clinical and histopathological parameters. Calculations are based on a total of 44,258 histopathologically examined skin neoplasms, including 529 melanomas, which were recorded in the histological database of the Department of Dermatology, University of Graz during a 2 year period. The clinical diagnosis of the referring physicians was compared statistically with the final histopathological interpretation. Clinical diagnosis of melanoma showed a sensitivity of 70.1%, a specificity of 99.4%, and a positive predictive value of 60.7%. One hundred and fifty eight melanomas (29.9%) could not be diagnosed clinically. The age-dependent sensitivity was 47.6% in patients <40 years, whereas for patients >80 years the value was 90.2%. Remarkably, the sensitivity in melanomas >4 mm thickness (64.8%) was lower than in 'melanoma in situ' (72.6%). Our findings underline the importance of further development of clinical examination techniques such as dermoscopy and digital epiluminescence microscopy.

Adult↗
PubMed1998

Operations on patients deemed "unfit for operation and anaesthesia": what are the consequences?

BACKGROUND: The decision "patient unfit for anaesthesia and operation" is likely to cause a delay of the scheduled operation. This retrospective evaluation was done: 1) to determine the correctness of preoperative tentative diagnoses of coexisting diseases making anaesthesia and operation excessively risky in relation to the physician's training status; 2) to examine the question of whether preoperative medical management modified according to the anaesthesiologist's suggestions had a positive impact on the perioperative course. METHODS: The medical records of patients scheduled for elective non-cardiac surgery who were rated "unfit for operation and anaesthesia" were evaluated. The accuracy of the tentative diagnoses was examined for relation to the training status of the anaesthesiologists. The preoperative management was tested for its impact on postoperative outcome. RESULTS: During the observation period 16,122 patients underwent preoperative anaesthesiological assessment; 1021 (6.3%) were initially considered to be unfit for operation and anaesthesia. The records of 807 patients were available for review. The accuracy of the tentative diagnoses was 70%, and was not significantly affected by the training status of the physicians (P = 0.022). Four hundred and seventeen patients were excluded from the second part of the investigation (discharged without operation, underwent operation using local anaesthesia or tentative diagnosis not confirmed). Three hundred and ninety patients were operated under general anaesthesia. Group I (n = 216) was managed according to the anaesthesiologist's suggestions and was found to have a significantly lower complication rate (18.1%) than group II (n = 174) in which the suggestions from the preoperative assessment were ignored (32.2%; P < 0.05). The perioperative mortality rate in group I was 2.3% compared with 5.2% in group II (n.s.; P > 0.05). CONCLUSIONS: We conclude that the anaesthesiology decision "patient unfit for operation and anaesthesia" has a high accuracy, independent of the anaesthesiologist's training status, and that preoperative medical management significantly reduces complications.

Anesthesia↗
PubMed1998

CD44 and variants in melanocytic skin neoplasms.

Expression of cell surface molecules that mediate cell-matrix and cell-cell interactions largely contributes to the ability of melanoma cells to migrate and spread beyond the primary site of the tumor. CD44, the principal cell-surface receptor for hyaluronate, and its numerous splice variants have been reported to play a crucial role in invasion and the metastatic process of different human neoplasms, including primary malignant melanoma (PMM). The aim of this study was to clarify which isoforms of CD44 (standard CD44 and CD44 variants) are distributed in PMM with a vertical tumor thickness of >1.4 mm. Staining of CD44 standard (CD44s) and splice variants was further examined for diagnostic and prognostic relevance in a panel of melanocytic skin lesions. Ten cases of PMM with Breslow >1.4 mm were analysed by immunohistochemistry using monoclonal antibodies specific for CD44s and the splice variants v3, v5, v6, v7, v7-8, and v10. In addition, using anti-CD44s, v5, and v6 antibodies, 55 melanocytic lesions, including dermal nevi (n=12), Clark nevi (dysplastic nevi) (CN; n=11), melanoma in situ (Mis; n=8), PMM (n=18), and cutaneous metastasis of malignant melanoma (cMMM; n=6) were assessed. Staining intensities were scored visually and evaluated by means of a staining index. In ten cases of PMM with a Breslow index >1.4 mm positive staining was ascertained for CD44s, v5 and for v6 in three cases. No staining was found for v3, v7, v7-8, and v10. Examination of CD44s, v5, and v6 in 55 melanocytic skin lesions revealed a high index for CD44s in all specimens and a weak staining of v5 in Mis; dermal nevi and CN did not stain for v5. However, in PMM and cMMM we found v5 to be strongly positive. The isoform v6 showed a variable index only in PMM, but without connection to established prognostic criteria. We conclude that CD44s and splice variants can not be regarded as indicators for tumor progression in malignant melanomas. However, v5 may potentially serve as a diagnostic marker for melanocytic skin lesions.

Adolescent↗
PubMed1998

Cellular automaton simulation of tumour growth -- equivocal relationships between simulation parameters and morphologic pattern features.

OBJECTIVE: To develop an interpretation procedure which estimates simulation parameters (tumour cell motility, tumour cell adhesion, autocrine and paracrine growth control, stroma destruction) of simulated patterns solely based on morphometric features of the morphologic pattern. METHODS: A cellular automaton computer simulation program was developed which produces morphologic patterns by growth of a seed of tumour cells. At the beginning of each simulation run certain simulation parameters are assigned to the tumour cells. After the run has been completed, the resulting pattern is evaluated by a set of morphometric features. Simulation parameters and resulting morphometric features of 27,800 simulations were stored in a database and were used for the evaluation of potential relationships. RESULTS: Correlation analysis showed highly significant correlations between morphometric features on the one hand and the preset simulation parameters (tumour cell motility, tumour cell adhesion, autocrine and paracrine growth control, stroma destruction) on the other. Correlation coefficients, however, varied from 0.72 to 0.99. When only one simulation parameter varied while all others were kept constant, morphometric features yielded a highly reliable estimate of the particular simulation parameter. When variability was extended to 4 simulation parameters, morphometric features were less effective in estimating the setting of the parameters. Though in all patterns tested several possible simulation parameter constellations could be ruled out, morphometric features were usually compatible with more than one set of simulation parameters thus preventing a straightforward interpretation. CONCLUSIONS: Though simulation parameters significantly and reproducibly influence the resulting morphologic pattern as characterized by morphometric features, estimates of the simulation parameters based on morphometric features yield equivocal results.

Cell Division↗
PubMed1998

Fractal tumor stromal border in a nonequilibrium growth model.

OBJECTIVE: To examine the potential relationships of tumor growth parameters and fractal dimensionality of the resulting pattern. STUDY DESIGN: A nonequilibirum tumor growth model was developed taking into account tumor cell motility, tumor and stromal proliferation, cohesion, autocrine and paracrine growth stimulation, and tumor and stromal destruction. Ten thousand simulation runs were performed with varying settings of the control parameters. Fractal dimensionality of the tumor-stroma border was assessed in each pattern by a box counting method. RESULTS: Fractal dimensionality increased with overall tumor cell motility, heterotypic tumor-stroma adhesion and paracrine growth stimulation, and decreased with homotypic tumor-tumor adhesion, autocrine growth stimulation, and tumor and stroma destruction. CONCLUSION: Fractal dimensionality of the tumor-stroma border depends on various parameters controlling tumor growth. Some growth properties considered to be associated with an increased degree of malignancy influence fractal dimensionality in opposite directions. Therefore, determination of fractal dimensionality cannot be related directly to any particular biologic feature or to the overall biologic behavior of a tumor.

Autocrine Communication↗
PubMed1997

Influence of UVB therapy on dermoscopic features of acquired melanocytic nevi.

BACKGROUND: Exposure to UV radiation can lead to clinical, histologic, and ultrastructural changes in acquired melanocytic nevi. OBJECTIVE: We investigated whether UVB therapy can induce changes in melanocytic nevi detectable by dermoscopy. METHODS: Eighty acquired melanocytic nevi of 13 patients (10 females, 3 males; mean age, 28 years; range, 13 to 62 years) undergoing UVB therapy were documented under standardized conditions by means of a Dermaphot apparatus before and at the end of suberythemal UVB therapy. The mean duration of therapy was 8 weeks (range, 2 to 17 weeks) and the mean total UVB dose was 1120 mJ/cm2 (range, 247 to 2771 mJ/cm2). During UV irradiation, 40 nevi were left unprotected and 40 nevi were protected from UV exposure in a randomized manner. Color dermoscopic images of nevi before and after UVB therapy were projected side by side and examined blindly by five investigators. Fifteen different features were evaluated in the nevi. RESULTS: Unprotected nevi became more irregular (p < or = 0.01) and darker brown (p < or = 0.03) by the end of the therapy, whereas the protected nevi showed no significant changes. CONCLUSION: Suberythemal UVB therapy can lead to changes in the dermoscopic image of acquired melanocytic nevi, presumably by activating melanocytes.

Adolescent↗
PubMed1997

Circulating adhesion molecules as prognostic factors for cutaneous melanoma.

BACKGROUND: Overexpression of adhesion molecules in tissues of human neoplasms, including malignant melanoma, has been reported to be clinically relevant, but the predictive value of circulating adhesion molecules for clinical outcome and life expectancy in patients with primary malignant melanoma (PMM) and metastases of primary malignant melanoma (MMM) remains undetermined. OBJECTIVE: Our purpose was to examine the prognostic relevance of circulating adhesion molecules, namely circulating CD44 standard (cCD44std), and the isoforms CD44v5 (cv5), CD44v6 (cv6), and CD44v10(cv10), circulating intercellular adhesion molecule-1 (cICAM-1), and circulating platelet/endothelial cell adhesion molecule-1 (cPECAM-1, CD31). METHODS: Levels of cCD44std, cv5, cv6, cv10, cICAM-1, and PECAM-1 were measured by enzyme-linked immunosorbent assays in 119 patients with PMM and MMM, in 12 persons with dysplastic nevi (Clark's nevi), and in 28 patients with inflammatory cutaneous diseases. RESULTS: Patients with PMM, MMM, and inflammatory cutaneous diseases showed an elevation in levels of cCD44std and cICAM-1 compared with normal blood donors, but these levels were not significantly increased. Levels of cv5, cv6, and cv10 were not increased, and cPECAM-1 was only marginally elevated. Even in patients with clinically provable systemic or cutaneous metastases and in five patients who died of MMM, levels did not differ significantly compared with normal blood donors; this was also independent of the mode of therapy. CONCLUSION: Circulating CD44std and the isoforms cv5, cv6, and cv10, cICAM-1, and cPECAM-1 were detectable in persons with dysplastic nevi and in patients with PMM and MMM. None of the measured adhesion molecules was significantly elevated and of prognostic relevance in any of the subgroups studied. However, some of the patients with PMM and MMM showed high levels of cCD44std and cICAM-1; that finding should prompt us to examine these patients in more detail.

Adult↗
PubMed1997

A comparison of the end-tidal-CO2 documented by capnometry and the arterial pCO2 in emergency patients.

Satisfactory artificial ventilation is defined as sufficient oxygenation and normo- or slight arterial hypocarbia. Monitoring end tidal CO2 values with non-invasive capnometry is a routine procedure in anaesthesia, emergency medicine and intensive care. In anaesthesia the ventilation volume is adjusted to the capnometric end tidal CO2 (ETCO2), taking into account a normal variation from the pACO2 of 3-8 mmHg. We evaluated the usefulness and practicability of using ETCO2 for correctly adjusting ventilation parameters in prehospital emergency care, by comparing arterial pCO2 and ETCO2 of 27 intubated and ventilated patients. We used the side-stream capnometry module of the Defigard 2000 (Bruker, ChemoMedica Austria) and a portable blood gas analyzer (OPTI 1, AVL Graz, Austria). Evaluation of the group of patients as a whole showed that there was no correlation whatsoever between the end expiratory and arterial CO2. Dividing the patients into three subgroups (1, During CPR; II, respiratory disturbances of pulmonary and cardiac origin; III, extrapulmonary respiratory disturbances), we found that only patients without primary cardiorespiratory damage showed a slight, but not statistically significant, correlation. This can be explained by the fact that almost any degree of cardiorespiratory failure causes changes of the ventilation-perfusion ratio, impairing pulmonary CO2 elimination. We conclude, that the ventilation of emergency patients can only be correctly adjusted according to values derived from an arterial blood gas analysis and ETCO2 measurements cannot be absolutely relied upon for accuracy except, perhaps, in patients without primary cardiorespiratory dysfunction.

Adult↗
PubMed1997

Comparison of two preoperative indices to predict perioperative mortality in non-cardiac thoracic surgery.

OBJECTIVE: The preoperative classifications: physical status of the American Society of Anesthesiologists (ASA-PS) and/or cardiac risk index (CRI) of Goldman are widely used to estimate the perioperative risk in patients undergoing noncardiac throacic surgery. We tried to determine the validity of both methods in predicting the perioperative mortality in 845 consecutive patients scheduled for major elective noncardiac thoracic surgery. METHODS: Preoperatively, each patient was assigned 2 independent estimations of risk according to the ASA-score (ASA grade, I-IV) and CRI score (CRI grade, I-IV), respectively. RESULTS: Twenty-five patients died within 4 weeks after the operation, the others survived the perioperative period. The grading according to ASA as well as to the CRI score showed a direct correlation with the outcome: The higher the preoperative score, the higher was the mortality rate. When various combinations of ASA and CRI were tested, the lowest mortality rate was found in presence of ASA < or = III and CRI = I. Multivariate regression analysis showed that the ASA score had an independent correlation with perioperative mortality, whereas such a relationship was absent for CRI. CONCLUSIONS: The subjective assessment by an experienced anesthesiologist as expressed by the ASA-score is a valid method in the determination of the perioperative risk. CRI does not contribute additional information for the general perioperative risk.

Adult↗
PubMed1997

Primary clinical response and long-term follow-up of solar keratoses treated with topically applied 5-aminolevulinic acid and irradiation by different wave bands of light.

Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is based on photosensitization by endogenous synthesis of protoporphyrin IX and its transient accumulation especially in malignant epithelially derived tissues. Recent studies have indicated that ALA-PDT is effective for the treatment of solar keratoses (SK), but there has been a lack of long-term clinical follow-up. The goal of the present study was to investigate the immediate and long-term effect of ALA-PDT on SK. Twenty-eight patients with a total of 251 SK were enrolled in the study. Standard treatment involved the topical application of 20% ALA, under occlusive and light-shielding dressing for 4 hours before exposure to UVA and/or different wave bands or wave band combinations of polychromatic visible light (full-spectrum visible light, and/or different wave bands of filtered visible light > 515, > 530, > 570, or > 610 nm) in one or two treatment sessions. The primary complete response rate of SK to ALA-PDT was 64% after one treatment, but 85% when the responses to a second treatment were included. Taken all treatments together, the complete response rate for lesions on face, scalp and neck was 93% for full-spectrum visible light, 96% for the combination of full-spectrum visible light and filtered light, 91% for different wave bands of filtered visible light, and 100% for the combination of long wave UVA and full-spectrum visible light, respectively. The complete response rate for lesions on forearms and hands was 51% for full-spectrum visible light and 33% for the combination of full-spectrum visible light and filtered light. The greater response rate for SK on the face, scalp, and neck was associated with a higher surface fluorescence and immediate response rate after ALA photosensitization at these sites (chi 2; p = 0.0001). However, due to the treatment protocol the mean light dose applied to lesions on the face, scalp and neck (50 J cm-2) was substantially higher than that for lesions on forearms and hands (35 J cm-2). In the long term follow-up of SK on face scalp and neck, the projected disease-free rate at 36 months after therapy was 71% for lesions treated with full-spectrum visible light versus 23% for lesions treated with different wave bands of filtered light (Log rank-Mantel Cox; p = 0.0001). These results indicate that treatment with full-spectrum visible light at higher light doses may be the most effective and promising form of light exposure in ALA-PDT of SK.

Administration, Topical↗