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Biomedical subjects

J Smolle

Publications and source records attributed to J Smolle.

At least 73 records · Page 4Linked to original sources
PubMed1997

Can ASA grade or Goldman's cardiac risk index predict peri-operative mortality? A study of 16,227 patients.

This trial was designed to study the correlation between peri-operative mortality in patients undergoing elective surgery and the physical status classification of the American Society of Anesthesiologists, the Goldman multifactorial cardiac risk index or the two indices combined. All patients scheduled for elective surgery over a 5-year period were evaluated pre-operatively and were scored according to both indices. Of 16,227 patients studied, 215 died within 4 weeks of operation. Both indices correlated significantly with peri-operative mortality, the ASA grade showing a closer correlation. A regression tree analysis divided the combination groups into five subgroups where the mortality was lowest (0.4%) in ASA grade < or = 2 and cardiac risk index group I (score 0-5 points) and increased up to 7.3% in ASA grade = 4 and cardiac risk index group > or = 3 (score > 13 points). We conclude that for this large number of patients peri-operative mortality can be predicted with the ASA grade and, to a lesser degree, with the cardiac risk index. Applied in the correct way, the combination of the two scores can increase the accuracy of prediction of peri-operative mortality.

Adult↗
PubMed1997

Does surgical removal of primary melanoma trigger growth of occult metastases? An analytical epidemiological approach.

BACKGROUND: In several human tumor systems a potential role of surgical removal of the primary tumor upon metastatic tumor growth has been evaluated, as it has been in experimental models. The present study addresses the question of whether the removal of primary melanomas disinhibits growth of metastatic disease and results in more rapid progression. METHODS: In a data set of 1224 primary cutaneous melanomas the risk of "thin" melanomas to develop metastases within 1 year was compared with the risk of matched pairs of "thick" melanomas to present metastases at the time of diagnosis. For this purpose, a pairwise matching procedure based on certain assumptions as to tumor volume and tumor doubling time has been applied. RESULTS: When a long tumor doubling time is assumed (200, 400, or 800 days), the tumors removed seem to have a significantly higher risk of metastases to become clinically apparent within 1 year than the matched pairs of tumors to present metastatic disease at the time of diagnosis (chi-square < 0.01). When short tumor doubling time is assumed (50 or 100 days), the difference is not significant, but there also seems to be no benefit for the operated patients. CONCLUSION: In the present data set there is evidence that surgery of primary melanoma may enhance tumor growth at metastatic sites.

Austria↗
PubMed1997

Cytoplasmic microtubules in two different mouse melanoma cell lines: a qualitative and quantitative analysis using confocal laser scanning microscopy and computer-assisted image analysis.

The microtubular system as one part of the cellular cytoskeleton is not only necessary for mitotic activity of malignant cells but also for invading neighboring tissues and for the formation of distant metastases. In the present study, the amount and distribution of tubulin in two murine melanoma cell lines (K1735-M2: high metastatic clone; K1735-c116: low metastatic clone) were determined quantitatively using an indirect immunofluorescence technique, confocal laser scanning microscopy (CLSM) and computer-assisted image analysis. Additionally, qualitative and quantitative changes after application of the microtubule-inhibitor nocodazole were investigated. Quantitative analysis showed a significant difference between the high and low metastatic cell line for the parameter TEXTURE, indicating a finer structured network within the high metastatic cells. After treatment with nocodazole the parameters TEXTURE and DENSITY were reduced, suggesting a decrease of assembled tubulin and a less delicate structure of the remaining microtubules. Our study shows that CLSM combined with computer-assisted image analysis provides a new method to examine quantitative variations of the cytoskeleton possibly related to cell function.

Animals↗
PubMed1997

Interrelation of motility, cytoskeletal organization and gap junctional communication with invasiveness of melanocytic cells in vitro.

Intercellular communication and the active movement of malignant cells into and through host tissue barriers play a critical role during the complex process of tumor invasion. Motile activity, cytoskeletal actin and vinculin organization as well as gap junctional communication of in vivo benign and malignant melanocytes were compared and related to in vitro invasiveness. Normal melanocytes, Melan-a, showed significantly less motile activity, a higher organization of the actin cytoskeleton and more vinculin-containing cell-substratum adhesion plaques than highly metastatic melanoma cells, K1735-M2. There was no pronounced difference in gap junctional communication under comparable culture conditions. However, cultivation of Melan-a cells in a conventional melanocyte growth medium containing the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced intercellular communication. Melanocytes were less invasive than melanoma cells both in the embryonic chick heart model and in the Matrigel invasion assay. The least invasive activity was determined for melanocytes cultivated in TPA-deficient medium indicating that the medium supplement TPA stimulates invasion. The comparison of certain in vitro properties of both melanocytic cell lines revealed a positive correlation of motility with in vitro invasion, whereas an inverse correlation was found for the degree of actin filament organization as well as for the number of vinculin plaques. Gap junctional communication was not directly related to in vitro invasiveness.

Actins↗
PubMed1996

Pathological findings suggestive of interclonal stabilization in a case of cutaneous melanoma.

Metastatic spread is a complex process based on manyfold interactions of the tumor cells with each other and with the surrounding stroma. In experimental systems tumor cell heterogeneity and presence of various subpopulations which interact with one another to stabilize their relative proportions within the population has been shown. Here we report a patient with melanoma, showing morphological evidence of two distinct tumor cell populations in the primary tumor and in all subcutaneous metastases. By image analysis, both populations were clearly characterized by minimal nuclear diameter and by nuclear form factor and were demonstrable in each specimen. The fact that these peculiar cell populations were present in all melanoma lesions removed from the patient might indicate that the populations require the presence of each other and that none of them is metastatically competent on its own.

Cell Division↗
PubMed1996

Differential effects of synthetic sphingosine derivatives on melanoma cell motility, growth, adhesion and invasion in vitro.

Cancer cell surface glycosphingolipids are considered to play a critical role in tumor growth and metastasis. However, the implications of glycoconjugates in the control of cell motility, which is considered to be involved in tumor invasion, are not fully understood. In this study, the effects of a series of synthetic sphingosine derivatives, obtained by the chemical transformation of azidosphingosines, on directional migration of K1735-M2 melanoma cells grown on type I collagen-coated surfaces were investigated. Following the application of 60 microM (2R, 3S, 4E)-2, 3-epimino-4-octadecen-3-ol (S4) the migration rate was 94 +/- 10 microns/day, compared with 377 +/- 22 microns/day in the control experiment. Six other analogues were not as potent. S4 also considerably down-modulated melanoma single cell motility. Inhibition of motile activity was associated with changes in the actin filament organization as well as with changes in the number and distribution of vinculin plaques. Moreover, the compound reduced the attachment abilities of melanoma cells to basement membrane Matrigel. Tumor cell invasion, however, was less affected and proliferation remained unimpaired after treatment with S4. These data suggest at least one intracellular mode of action of this particular synthetic sphingosine derivative by modulation of cytoskeletal organization. Melanoma cell motility and growth may be controlled independently via glycosphingolipids.

Actins↗
PubMed1996

Influence of skin tension and formalin fixation on sonographic measurement of tumor thickness.

BACKGROUND: High-resolution sonographic measurement of skin tumors, especially of malignant melanomas, allows presurgical assessment of the most important prognostic factor--tumor thickness. A good correlation between ultrasonographic and histopathologic thickness measurement has been reported. Procedures for preparing tissue for histopathologic examination, such as excision, fixation in formalin, dehydration in alcohol, and embedding in paraffin, may cause the tissue to retract and shrink and may therefore affect thickness measurement results. OBJECTIVE: Our purpose was to evaluate the influence of skin preparation procedures on ultrasound measurement results and to compare tumor thickness values obtained sonographically versus those obtained histopathologically. METHODS: Sixty-three epithelial (n = 37) and melanocytic (n = 26) tumors, benign as well as malignant, were measured by ultrasound before and immediately after excision and after overnight fixation. Sonographically and histopathologically determined tumor thicknesses were compared. RESULTS: Loss of skin tension after excision led to an increase in measured tumor thickness because of spherical retraction of the specimen. Subsequent fixation, dehydration, and embedding reversed this effect, so that altogether, histopathologically assessed tumor thickness was only slightly lower than ultrasound-derived thickness before excision. This was true for melanocytic as well as epithelial lesions. CONCLUSION: Loss of skin tension after excision and tissue preparation procedures seem to offset each other and lead to a good overall correlation between ultrasonographic and histopathologic measurements.

Adolescent↗
PubMed1996

Melanoma and stroma: an interaction of biological and prognostic importance.

Stromal relationships are crucial to metastatic spread of solid malignancies. Some aspects of this stroma interaction are obviously associated with particular morphological features, which may carry prognostic significance. In cutaneous melanoma, level of invasion, arrangement of cells (horizontal or vertical growth phase), neovascularization, vessel invasion, architecture of the border, and inflammatory infiltrate have been examined. Expression of adhesion molecules, signalling factors, cytoskeletal components, extracellular matrix molecules and matrix-degrading enzymes have been assessed by immunohistology and in situ hybridization. Besides providing prognostic information, a thorough evaluation of stromal relationships may help to increase our knowledge about factors mediating the growth and metastatic spread of malignancies.

Disease Progression↗
PubMed1996

Quantitative morphology of collagen fibers in cutaneous malignant melanoma and melanocytic nevus.

Since tumor growth and metastastatic spread are considered to depend on tumor-stroma interaction, the present study describes the architecture of collagen fibers in 12 cases each of primary melanoma (vertical tumor thickness > 1 mm) and common melanocytic nevi in azan-stained sections by using automated image analysis. In each case, at least 100 high-power fields were consecutively sampled from the tumor center, the tumor periphery, and the surrounding normal-appearing reticular dermis. In both diagnostic groups, collagen density (amount of collagen per tissue volume) and mean collagen fiber bundle diameter was significantly lower in the tumor periphery than in the surrounding stroma and again lower in the tumor center than in the tumor periphery. When melanomas and nevi were compared with each other, melanomas had fewer, but thicker, collagen bundles than did nevi, particularly at the tumor periphery. Taking the mean values of each case as classifiers in multivariate logistic regression analysis, 21 of 24 cases were correctly classified (chi-squared test, p < 0.0001), indicating that the parameters of collagen architecture at least in part reflect biological differences between benign and malignant melanocytic skin lesions.

Adult↗
PubMed1996

Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia: a clinicopathologic and prognostic study of 42 patients.

The clinical and histopathologic features of specific skin infiltrates in patients with B-cell chronic lymphocytic leukemia (B-CLL) have rarely been reported in detail. In this study we analyzed the clinical, histopathologic, immunophenotypic, and molecular features of 84 skin lesions from 42 patients (M:F = 1.3:1; mean age, 66.0 years; range, 42-83 years) with specific cutaneous manifestations of B-CLL. The duration of B-CLL before skin manifestations varied from 0 to 142 months (mean, 39 months). In seven patients (16.7%), skin lesions represented the first sign of disease. Clinical presentations included localized or generalized erythematous papules, plaques, nodules, and large tumors. Ulceration was uncommon. In six patients lesions were confined at the sites of scars from previous herpes zoster (four patients) or herpes simplex (two patients) eruptions. Histologically, three main patterns were recognized: (a) patchy perivascular and periadnexal, (b) nodular-diffuse, and (c) band-like. Cytomorphologically, small monomorphous lymphocytes predominated. Proliferation centers were observed in only four specimens. In two patients presenting with tumors, a high content of large cells with feature of centroblasts and immunoblasts was found (Richter's syndrome). Immunohistologic analyses were performed on paraffin-embedded specimens in 40 biopsies from 20 patients and on cryostat sections in 17 biopsies from 11 patients. Neoplastic B lymphocytes in all cases showed an aberrant phenotype (paraffin sections: CD20+/CD5+/CD43+; cryostat sections: CD19+/CD5+; immunoglobulin light-chain restriction). Proliferation markers (Ki67, PCNA, MIB1) stained 5 to 80% of cells (mean, 25%; median, 20%). Polymerase chain reaction performed in nine cases on paraffin-embedded tissues using consensus primers for immunoglobulin heavy-chain genes showed a monoclonal population of B lymphocytes in all cases. Several discrete bands in addition to the prominent ones were noted in five cases, indicating the additional presence of B lymphocytes whose immunoglobulin genes were not monoclonally but oligoclonally rearranged. Follow-up data could be obtained from 31 patients. The two patients with Richter's syndrome died after 5 and 8 months, respectively. The 5-year survival of patients with small-cell cutaneous B-CLL was 66.6%. Our study indicates that cutaneous specific manifestations of B-CLL present with characteristic histologic, immunophenotypic, and molecular patterns. Prognosis in these patients is probably not affected by skin involvement.

Adult↗
PubMed1996

Prognostic evaluation of specific cutaneous infiltrates in B-chronic lymphocytic leukemia.

The relationship between numerous histologic variables and survival was investigated in 54 consecutive lesions of specific skin infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) from 27 patients (16 males and 11 females, mean age 65 years, range 42-83 years). All patients were followed for up to 204 months or until death. Histopathologically, the infiltrates showed a patchy perivascular (35%), diffuse (31.5%), nodular (31.5%) or bandlike (1.9%) pattern. In 28% of the cases, an admixture of reactive cells within the infiltrate including eosinophils, histiocytes, neutrophils and plasma cells was observed. Cytomorphologically, small B-lymphocytes with condensed chromatin predominated in most infiltrates. However, some biopsies showed a small but significant number of medium- or large-sized neoplastic cells of the B-lymphocyte lineage with variable cytomorphological features. In a multivariate analysis, several histologic parameters within the infiltrates were found to show a significant association with long survival, namely, an infiltrate of moderate density, a nodular pattern, involvement of the lower dermis only, and presence of predominantly small B-lymphocytes (more than 95%) with condensed chromatin. Histologic variables that independently correlated with relatively short survival included an infiltrate of severe intensity, a diffuse pattern, epidermal changes (especially acanthosis and ulceration), medium-sized and large B-lymphocyte (more than 5%), and reactive cells within the infiltrate (neutrophils, eosinophils, and plasma cells). Overall analysis of our results showed two histologic patterns with a significant prognostic impact (p < 0.01; z = 5.4). Pattern I (33 biopsies) correlated with relatively long survival (2-year survival rate; 97%) and consisted of infiltrates showing predominantly small B-lymphocytes (more than 95%) without reactive cells or epidermal changes. Pattern II (21 biopsies) indicated short survival (2-year survival rate; 49%) and included all the rest of the biopsies i.e., infiltrates with medium- and large-sized B-lymphocytes (more than 5%), admixture of reactive cells, and epidermal changes. Results from our study suggest that histologic features in specific skin infiltrates of B-chronic lymphocytic leukemia may be helpful in identifying prognostically different subgroups of patients and planning therapeutic schedules.

Adult↗
PubMed1996

Clinical and histological features of poor prognosis in cutaneous metastatic melanomas.

Patients with melanoma metastatic to the skin show variable prognosis. Though some may survive for quite a long time, some die of disseminated disease within 1 year of removal of cutaneous metastases. The aim of this study was to find out whether there are any histological criteria indicating particular poor outcome. Clinical and histological features of 344 melanoma lesions metastatic to the skin were assessed and their prognostic relevance was investigated. H&E stained histological slides were scanned for the presence of morphological criteria expressing certain tumor cell-stroma interactions: capsule formation (CAPSULE), formation of intratumoral septa (NEWSEPTA), simple invasion between collagen of reticular dermis (DERM-SIMPLE), or subcutis (SCSIMPLE), preservation of preexistent collagen (PRECOLL) or fatty tissue (PREFAT) and, finally, histological site of metastasis. Additionally, anatomical location of the metastases, time between removal of primary tumor and metastases age and sex of patients were recorded. The metastases were divided into two groups: lesions of patients who died within 1 year after resection (n = 59) and lesions from patients with a longer survival (n = 285). Metastases which were associated with death within one year were significantly more often found in male patients (54.2% versus 34.7%), in younger patients (mean age 51.1 +/- 14.1 years versus 58.8 +/- 15.3 years), had developed earlier after the primary tumor (mean time of 21.7 +/- 19.9 months versus 43.3 +/- 27.4 months) and were more often found at distant sites than in localregional sites (45.7% versus 30.5%), and were more often involved in the subcutis (74.5% versus 56.1%). From a histological point of view, DERMSIMPLE (80% versus 46%; p < 0.001) and PRECOLL (82.8% versus 57.6; p < 0.01) were more frequent in metastases of poor outcome. The same was true for SCSIMPLE (50% versus 25.6%; p < 0.01) and PREFAT (68.1% versus 46.8%; p < 0.05) in lesion with subcutaneous growth, whereas CAPSULE (54.5% versus 75%) was less frequently seen. In conclusion, melanoma deposits metastatic to the skin with particular poor outcome differ clinically and histologically from other cutaneous melanoma metastases. This should be taken into account in the design of therapeutic clinical trials.

Adult↗
PubMed1996

Homoeopathic versus placebo therapy of children with warts on the hands: a randomized, double-blind clinical trial.

BACKGROUND: Despite the wide practical application of homoeopathy, scientific proof of its effectiveness and mechanisms is still lacking, and sound, placebo-controlled studies are scarce. OBJECTIVE: The purpose of our study was to evaluate the efficacy of homoeopathy in a prospective, double-blind randomized trial. METHODS: 60 children aged 6-12 years with common warts on the back of the hands were treated either with an individually selected homoeopathic preparation (n = 30) of at least a 1:1,012 dilution or with pure placebo in the form of saccharose globuli (n = 30) under double-blind conditions. The area occupied by warts was measured by computerized planimetry before and after 8 weeks of treatment. Reduction of the warty area by at least 50% was considered a response. RESULTS: There were a total of 16 responders: 9 of 30 patients in the homoeopathic therapy group and 7 of 30 patients in the placebo group (chi 2 = 0.34, p = 0.56). Total cure of warts occurred in 5 patients in the treated group and in 1 patient in the placebo group (chi 2 = 1.46, p = 0.22). CONCLUSION: There was no apparent difference between the effects of homoeopathic therapy and placebo in children with common warts under the conditions of this study.

Child↗
PubMed1996

Zosteriform lichen planus.

A 42-year-old woman developed a papular eruption mainly localized on the right side of the body and with a zosteriform pattern within the nerve segments TH6-TH12, L1-L4 as well as S1 and S2. The skin lesions were characteristic of lichen ruber planus. The zosteriform arrangement of lichenoid papules is rare and is interpreted as a cutaneous reaction possibly triggered by some neural factor.

Adult↗
PubMed1996

Cellular invasion without cellular motility in a stochastic growth model.

Invasion of a tissue by distinct cell types is common to various biological processes including embryonic development and tumour growth. Active movement is usually considered to be a prerequisite for invasiveness. Using a computer simulation program based on a stochastic cellular automata model, we provide evidence that invasive patterns may evolve in the absence of active cellular motility. Cells characterized by low proliferation, a high rate of cell loss, pronounced tumour-stroma adhesion and an expansive instead of a destructive behaviour invade the surrounding matrix, despite a complete lack of active movement. The resulting morphological patterns are similar to those obtained with motile cells. Thus invasion does not necessarily indicate the presence of motility.

Cell Adhesion↗
PubMed1996

Assessment of tumor cell cohesion in vivo using pattern interpretation by cellular automata.

OBJECTIVE: There is abundant evidence that patterning in life sciences may be closely related to the functional properties of the constitutive elements. In order to estimate some of these functional properties by examining the static pattern evolved, pattern interpretation by cellular automata (PICA) was introduced and applied to the mechanisms of tumor growth. Previously it was shown that the estimates concerning tumor cell proliferation and motility were consistent with those obtained by other methods. STUDY DESIGN: Morphologic patterns obtained by growing two variants of the C4 cervical carcinoma cell lines with different in vitro adhesive properties in the hamster cheek pouch were evaluated by PICA. RESULTS: PICA estimates of tumor cell cohesion turned out to be significantly higher in tumors derived from the C4-I cell line (0.73 +/- 0.02 SD) with high in vitro cohesiveness than in tumors derived from the less adhesive C4-II cell line (0.32 +/- 0.04 SD; t test, P = .001). CONCLUSION: These results indicate that functional estimates concerning tumor cell cohesion obtained by PICA may be in good agreement with in vitro observations of the same cellular property and further underscore that PICA may be a useful tool for the functional interpretation of static histologic patterns.

Animals↗