The durability of NR-based elastomer material has been examined by stress relaxation and chemical analytical methods in order to investigate the impact of chemical ageing on relaxation processes. The secondary relaxation process, which is derived by separation from the stress relaxation curve, is found to be closely related to the oxidation induction time detected by chemiluminescence. It is suggested that thermal exposition during the initial phase of stress relaxation is mainly due to rearrangement of the filler network and polymer-filler interactions.

A concept to increase the precision of the prediction of long-term stress relaxation in elastomers from tests conducted over short time frames is discussed. A method to separate physical and chemical relaxation processes has been developed. The basis of the method is to evaluate the continuous relaxation time spectrum for each test temperature in order to separate the relaxation processes. Subsequently a summation of all processes may be used to produce a time and temperature dependent curve fit.

Increasingly, manufacturers need to provide warranties of over 10 years on rubber seals, gaskets and air-springs and warranties of between 20 and 30 years on O-rings for underground applications [Parker Hannifin Corp. Compression set vs. compression stress relaxation. vol. 1, No. 3; 2003.]. In order to expedite the development process, experimental concepts for accelerated forecasts of long-term relaxation are required. Previously the standard procedures have relied upon semi-quantitative methods which considered material behaviour at elevated temperatures. The objective of the work presented here is to develop precise forecasting procedures with the use of the time–temperature superposition principle, the Williams–Landel–Ferry (WLF) equation [J.D. Ferry. Viscoelastic properties of elastomers. 3rd ed.; 1980.] and the Arrhenius equation [ISO 11346. Rubber, vulcanised or thermoplastic – estimation of life-time and maximum temperature of use from an Arrhenius plot. 1997.].

The development of an axi-symmetric bubble inflation fatigue test rig is described. The rig allows the determination of real time stress/strain data for thin elastomeric sheets subjected to cyclic loading. It is intended that this data will be used to produce accurate mathematical models for finite element analysis (FEA) of hyperelastic and viscoelastic material behaviour during fatigue loading leading to failure. This work involves the development of a real time surface measurement system for the bubble profile in conjunction with a fully integrated hydraulic pressure control system. The systems provide a method of continuously monitoring bubble profile dimensions, inflation pressures, and associated stress-strain data during repeated inflations and deflations leading to failure. Recent publications have highlighted the dependency of the fatigue life of non strain-crystallising elastomers, subjected to uniaxial deformation, on both mean stress and stress amplitude. The bubble inflation tests will establish if a similar dependency exists for bi-axial deformation.

BACKGROUND Patients with T4 N0 M0 melanoma are considered at high risk for having occult metastases, and adjuvant therapy is usually recommended. HYPOTHESIS Long-term survival in patients with thick melanoma is not universally poor. DESIGN A retrospective study. SETTING University teaching hospital. PATIENTS We evaluated clinical node-negative thick (> or = l4.0 mm) melanoma in 151 patients who received their primary definitive surgical treatment in our department. None of these patients received any adjuvant therapy. RESULTS Median follow-up was 44 months; median thickness, 5.5 mm. Median overall (OS) and disease-free survivals (DFS) were 70 (5-year survival, 52%) and 51 months (5-year survival, 47%), respectively. Patients with node-positive disease faired significantly worse than did those with node-negative disease. Median OS and DFS for patients with node-positive disease were 49 and 32 months (5-year survival, 35%), respectively, compared with 209 (5-year survival, 61%) and 165 months (5-year survival, 56%), respectively, for patients with node-negative disease. Similarly, OS and DFS were significantly lower when the primary tumor had at least 5 mitoses/mm(2) or was located in the head and neck region. After multivariate analysis, status of the lymph nodes was the most predictive variable for OS and DFS. CONCLUSIONS The thickness of melanoma, by itself, should not be used as a criterion for adjuvant therapy. Other prognostic factors should be considered.

OBJECTIVE:To study clinical and histological features associated with metastasizing thin melanomas (MTMs).DESIGN:Case-control study of clinicopathological features of patients with MTMs by a panel of 10 dermatopathologists.SETTING:Members of the North American Melanoma Pathology Study Group selected the cases from the melanoma databases at 8 academic institutions.PATIENTS:Forty-three patients with MTMs (<1 mm thick) and 42 control subjects without metastasis matched for age, sex, tumor site, and Breslow thickness.INTERVENTION:None.MAIN OUTCOME MEASURES:Clinical (age, sex, site of lesion, stage at diagnosis, metastasis site, disease-free survival, and outcome) and histological (Breslow thickness, Clark level, growth phase, regression, and inflammatory response) features of patients with MTMs vs controls.RESULTS:There was an overrepresentation of axial tumors among patients with MTMs. Extensive regression was present in 18 patients (42%) with MTM vs 2 matched control subjects (5%) (95% confidence interval, 21%-53%; P =.001). Other histological variables were not significantly different. Two patients had melanomas in situ with subsequent metastasis.CONCLUSIONS:Thin melanomas with extensive regression represent a group at higher risk for the development of metastasis. Furthermore, the risk of metastasis cannot be dismissed in cases of melanoma in situ.

The biological nature of Spitz nevi/tumors and their diagnostic distinction from, or relationship to, melanoma remain unresolved issues. In this report, a series of 30 melanocytic lesions removed from 28 patients, including atypical Spitz nevi/tumors and metastasizing Spitzoid tumors/melanomas, were evaluated by a panel of dermatopathologists to evaluate interobserver diagnostic concordance and to assess the prognostic power of histological criteria. For inclusion in the study, each lesion had to display some criteria for the Spitz nevus, and in addition one of the following was required: (1) definitive clinical outcome such as metastasis or death of disease, or (2) long-term follow-up if the patient remained disease free. Each lesion was reviewed independently and blinded as to the clinical data by 10 pathologists, who categorized them as (1) typical Spitz nevus/tumor, (2) atypical Spitz nevus/tumor, (3) melanoma, (4) tumor with unknown biological potential, or (5) other melanocytic lesion. There was limited discussion of criteria before the review. Evaluation of 17 Spitzoid lesions yielded no clear consensus as to diagnosis; in only one case did six or more pathologists agree on a single category, regardless of clinical outcome. Notably, however, some lesions that proved fatal were categorized by most observers as either Spitz nevi or atypical Spitz tumors. Conversely, seven or more pathologists scored 13 lesions as melanoma. These results illustrate (1) substantial diagnostic difficulties posed by many Spitz tumors, especially those with atypical features, even among experts, and (2) the lack of objective criteria for their distinction from melanoma and for gauging their malignant potential. Nevertheless, our observations do suggest that a biological relationship exists between the Spitz nevus/tumor and melanoma.

BACKGROUND. The limitations of morphologic criteria alone in determining the prognosis for a patient with a particular intermediate-thickness primary melanoma have prompted efforts to identify other markers.METHODS, In this study, the authors analyzed expression of p53, beta 1 integrin, and beta 3 integrin in primary tumors from 111 patients with intermediate-thickness malignant melanoma.RESULTS. Eighty-nine (80%) had detectable p53 protein, 58 (52%) expressed pi integrin, and 71 (64%) expressed beta 3 integrin. Patients with beta 3 positive melanomas were more likely to die of their disease (32 of 71 patients, 45%) than those with beta 3 negative tumors (3 of 40 patients, 8%) (P < 0.0001). The number of involved lymph nodes, Clark's level, pi integrin expression, thickness, and mitotic rate also had prognostic significance. beta 3 integrin was associated with subsequent lung metastases and pi integrin with lymph node involvement.CONCLUSIONS. Integrin expression, along with histopathologic criteria, is a prognostic marker for intermediate-thickness malignant melanoma and may indicate the site of subsequent metastasis. These observations may have clinical utility and suggest areas for future investigation. (C) 1999 American Cancer Society.

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine tumor of the skin. Only little information is available on the genetic alterations occurring in this tumor. Cytogenetic studies thus far have not shown recurrent chromosomal changes, although various structural chromosome 1 rearrangements, including deletions, often leading to loss of distal 1 p material appear to be frequent. We report on fluorescence in situ hybridization and loss of heterozygosity analyses of an MCC tumor and MCC cell line UISO. The present study has shown that two distinct regions in the most distal band 1p36 on the short arm of chromosome I can be implicated in MCC. One region at 1p36.3 was delineated by a distal deletion in the MCC tumor as a result of an unbalanced translocation, resulting in loss of all markers distal to ENO1. This region was previously shown to be deleted in different tumor types including neuroblastoma. In cell line UISO an insertion in 1p36.2 was identified. The insertion breakpoint indicates a second, more proximal, region on Ip involved in MCC. The insertion breakpoint was mapped within a cluster of repetitive tRNA and snRNA genes and thus could coincide with the constitutional 1p36 breakpoint previously reported in a patient with neuroblastoma. (C) 1998 Wiley-Liss, Inc.

Barnhill, R L; Argenyi, Z B; From, L; Glass, L F; Maize, J C; Mihm, M C; Piepkorn, M; Rabkin, M S; Ronan, S G; White, W L Author Information

Previous studies have suggested that differential expression and/or activation of integrins facilitates metastatic progression in murine and human melanoma. While recent data show that the integrin αvβ3 is involved in tumor angiogenesis and that tumor growth may be abrogated by αvβ3 inhibitorsin vitro,the clinical significance of β3 integrin expression in human malignant melanoma is not known. To assess the prognostic value of β3 integrin expression, we examined primary cutaneous melanomas from 160 patients followed for a mean of 98 months or until death. We quantified the percentage of tumor area stained with β3 integrin Ab CD-61 using an image analyzer. β3 integrin expression was detected in 107/160 primary melanomas (69%). β3-integrin-positive (β3+) tumors were thicker (mean 2.98 ± 0.3 mm) than β3-integrin-negative (β3−) melanomas (mean 1.64 ± 0.2 mm) (P= 0.002). Patients with β3+ melanomas were more likely to relapse (57/107, 53%) and to die from disease (45/107, 42%) than those with β3− tumors (6/53, 11%; and 4/53, 8%, respectively) (P< 0.001). Overall survival was greater for β3− than for β3+ patients (mean 102 ± 9 vs 69 ± 6 months) (P= 0.001). These data show that β3 integrin expression in primary cutaneous melanoma predicts subsequent metastatic progression. Further study of β3 integrins in the development of melanoma metastases may yield new therapeutic strategies, as well as prognostic information, for the treatment of this cancer.

BACKGROUND:Experimental evidence suggests that integrins are key regulators of the development of melanoma metastases, influencing both the likelihood and site of metastases. Whereas effective treatment of cutaneous melanoma remains surgical, elective lymph node dissection (ELND) is controversial. The present study was designed to investigate the relationship between integrin expression by a given primary melanoma and occult regional lymph node metastases.MATERIALS AND METHODS:We studied beta 1 integrin expression, by quantitative immunohistochemistry using an image analyzer, in the primary melanomas of 90 ELND patients.RESULTS:beta 1 integrin was expressed in > or = 10% of the primary tumor in 92% of cases eith lymph node involvement versus 9% of node negative cases (p < 0.001).CONCLUSIONS:Our data demonstrate that quantitative immunohistochemistry for beta 1 integrin expression in primary melanomas can identify patients likely to have occult lymph node metastases. This suggests that beta 1 integrins play a role in the lymphatic dissemination of cutaneous melanoma.

Background. Elective lymph node dissection for malignant melanoma is still controversial. Experimental studies suggest that differential expression, activation, or both of PI integrins facilitate melanoma metastases. However, the clinical significance of beta(1) integrin expression in human melanoma is unclear.Methods. We examined primary cutaneous melanomas from 76 patients undergoing elective lymph node dissection. We quantified the percentage of tumor area stained by pr integrin antibody with an image analyzer.Results. beta(1) integrin was expressed in all 23 primary tumors from patients with pathologically positive lymph nodes (LNs) but in only 14 (26%) of 53 cases with pathologically negative nodes (p < 0.001). No patients with beta(1) integrin-negative tumors had LN involvement, whereas 23 (62%) of 37 patients with beta(1) integrin-positive tumors had LN metastases (p < 0.001). Furthermore, 21 (91%) of 23 cases with LN metastases but only 4 (8%) of 53 cases without had beta(1) integrin staining of 10% or more of tumor area (p < 0.001).Conclusions. Our study is the first to show a correlation between expression of a molecular marker in the primacy cutaneous melanoma and likelihood of regional LN metastases. beta(1) immunostaining of 10% or more of tumor area reliably predicts patients most likely to harbor occult LN metastases and likely to benefit from ELND.

Objective: To analyze whether the histologic subtype acral lentiginous melanoma confers independent prognostic significance.Design: Case series retrospective review.Setting: Academic surgical practice.Patients or Other Participants: Fifty-six patients with histologically confirmed acral lentiginous melanoma identified from patients with malignant melanoma consecutively treated by the faculty of the Department of Surgical Oncology at the University of Illinois at Chicago.Interventions: Not applicable.Main Outcome Measures: Lymph node metastases, disease-free survival, and overall concurrent or subsequent survival.Results: The average age of our patients with acral lentiginous melanoma was 61.1 years. Thirty-four (61%) were white, and the remaining 22 (39%) were African-American, Hispanic, or Asian. Thirty (54%) were male and 26 (46%) were female. The primary tumor occurred on the lower extremity in 46 (82%) of the cases and on the upper extremity in the remaining 10 (18%). Twenty-four primary tumors (43%) were greater than 4.00 mm thick. Analyzed by means of a logistic regression model, the rate of lymph node metastases did not significantly differ among patients with acral lentiginous melanoma, superficial spreading melanoma, and nodular malignant melanoma. Furthermore, when corrected for tumor thickness, disease-free and overall survival were the same for the three histologic groups. Multifactorial analysis identified only thickness as a prognostic variable for disease-free survival and overall survival.Conclusions: Despite the greater age, diverse ethnic background, and distinctive tumor characteristics of our patients with acral lentiginous melanoma, this histologic subtype does not, in itself, affect the outcome of these patients.

Nucleolar organizer regions (NORs) are loops of ribosomal DNA (rDNA) in the nucleolus and are associated with acidic proteins. They are seen in routinely processed paraffin sections by using a one-step colloidal silver (Ag) staining method; they appear as black dots termed "AgNORs". The quantitative assay of AgNORs has been used to differentiate benign from malignant neoplasms. Melanocytic lesions differ significantly in AgNOR counts between malignant melanoma and nevi. However, conflicting results have been reported as to AgNORs' prognostic value in melanoma. A recent study showed AgNOR counts to be a more accurate prognostic indicator than Breslow's thickness. In this study, we counted the AgNORs in 26 patients with primary cutaneous melanomas (CMM) between 2.0 mm and 2.5 mm thick. Of these, 14 are alive without disease (AN) at 5 years after diagnosis (group 1) and 12 are dead of disease (DD) in less than 5 years (group 2). The AgNORs were scored in 30 nuclei per tumor, and the means were calculated. For group 1, the mean number of AgNORs per nucleus was 6.88, ranging from 3.73 to 12.70. For group 2, the mean number was 6.97, ranging from 3.63 to 11.67. Statistical analysis using analysis of variance (ANOVA) showed no significant difference between the groups (p = 0.33). In our study, AgNOR counts did not prove to be of prognostic value in malignant melanoma.

Forty-eight cases of melanoma occurring in patients under 20 years of age were reviewed from a 23-year period at a single center. Fourteen of the patients were preadolescent children and 44 were Caucasian. Histological review of 44 available primary tumors showed only superficial spreading and nodular types. Thickness ranged from 0.23 mm to 8.50 mm, with a median of 1.03 mm. Ulceration was present in 7%, necrosis in 35%, evidence of regression in 16%, and antecedent nevus in 49% of the cases. The overall 5-year survival is 77%, with a median follow-up of 48 months. There is no detectable survival difference between preadolescent children and adolescents. Several treatment failures occurred after improper biopsy and/or inaccurate original diagnosis of Spitz's nevus. Of 38 stage I and II patients given definitive surgical treatment by the authors, the 5-year survival is 90%. Although histological confusion with Spitz's nevi occasionally occurs, melanoma in this age group can be treated with good results.