Search

In light of the significant clinical benefits of novel HER2-targeting antibody-drug conjugates in advanced HER2-low expressing breast cancers in recent phases I and III clinical trials, particularly trastuzumab-deruxtecan (T-Dxd), the new "HER2-low" category in breast cancers (breast cancer with a HER2 IHC score of 1+, or 2+ without gene amplification) has gained increasing attention. In the past year, "HER2-low" breast cancers have been under active investigation by both oncologists and pathologists. In this current review, we update the recent cutting-edge research on HER2-low breast cancers, with a focus on the biology of HER2-low breast cancers, the issues on the identification of HER2-low breast cancers by immunohistochemistry in current practice of pathology, and the future directions in this emerging category in breast cancers. more...

Recently, clinical trials have demonstrated promising efficacy for novel HER2-targeted therapies in HER2-low breast cancers, raising the prospect of including a HER2-low category (immunohistochemical [IHC] score of 1+, or 2+ with non-amplified in-situ hybridization [ISH]) in the HER2 evaluation of breast cancers. In order to better understand this newly-proposed HER2 category, we investigated the incidence, HER2 staining patterns, clinicopathologic features, and genomic profile of HER2-low breast cancers. HER2-stained slides of 281 consecutive breast cancers were re-reviewed and the clinicopathologic information, MammaPrint, and BluePrint results of these cases were retrospectively analyzed. HER2-low breast cancers were identified in 31% of cases and were more common in estrogen receptor (ER)-positive than ER-negative breast cancers (33.6% vs 15%, p = 0.017). HER2-low cancers were generally clinical stages I-II (79%), ER-positive (93.1%), had homogenous HER2 staining (59.2%), HER2 IHC score of 1+ (87.4%), ductal phenotype (81.6%), histologic grades of 1 or 2 (94.2%) and luminal molecular subtypes (94.3%). Three HER2-low patients received neoadjuvant chemotherapy and none of them achieved pathologic complete response. When compared to HER2-negative (IHC of 0+) and HER2-positive (IHC of 3+ or IHC of 2+ with amplified ISH) cancers, HER2-low breast cancers had significantly lower Ki-67 (p = 0.03 and p 0.01, respectively) and higher ER positivity (p = 0.01 and p = 0.03, respectively). HER2-low breast cancers were less likely to be basal molecular subtype when compared to HER2-negative cancers (p 0.01) and were less likely to have a HER2 molecular subtype when compared to HER2-positive cancers (p 0.01). When adjusted for ER status, there was no significant difference on all the examined variables between HER2-low and HER2-negative groups. Our study provides valuable baseline characteristics of HER2-low breast cancers deriving from consecutive, real-world cases with a consensus confirmation of HER2 status, and would help to increase our understanding of this newly-proposed HER2 category in breast cancers. more...

Background Progranulin (GP88) is a critical player in breast tumorigenesis. GP88 tumor expression is associated with increased recurrence and mortality, whereas GP88 circulating levels are elevated in patients with breast cancer compared with healthy individuals. We examined here the correlation between serum GP88 levels in patients with metastatic breast cancer (MBC) with overall survival and disease status determined as response to therapy or progression of disease. Patients and Methods An institutional review board (IRB)-approved study prospectively enrolled 101 patients with MBC at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. GP88 serum levels were correlated with patients’ disease status determined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and survival outcomes by Kaplan-Meier analysis and log rank statistics. Results Patients’ survival was stratified by serum GP88 level. Patients with serum GP88 55 ng/mL. Examination of GP88 serum levels in association with disease status showed a statistically significant association between serum GP88 levels and disease progression or response to therapy while CA15-3 level was only associated to progression. Conclusion The association of serum GP88 level with survival and disease status suggests the potential of using the serum GP88 test for monitoring disease status in patients with MBC. Measurement of serum GP88 levels in patients with MBC may have clinical value as a cost-effective adjunct to the management of patients with MBC with imaging. more...

As breast cancer treatment options continue to evolve, biomarker and multigene assay testing are now considered a standard part of the clinical evaluation of estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER-2) negative breast carcinomas. These methodologies are used to measure recurrence risk and to tailor both hormonal and chemotherapy treatment options. There are several international guidelines which address the use of biomarker and multigene assay testing for ER positive, HER-2 negative breast carcinoma. Each guideline has specific recommendations as to the prognostic and predictive value of the various biomarker and multigene assay methodologies, their clinical utility, and in some cases their cost effectiveness. In this review, we review the guideline recommendations from eight commonly referenced international organizations (American Joint Committee on Cancer, American Society of Clinical Oncology, Associazione Italiana di Oncologia Medica/ Italian Association of Medical Oncology, European Group on Tumor Markers, European Society for Medical Oncology, National Comprehensive Cancer Network, National Institute for Health and Care Excellence, and the St Gallen International Consensus Guidelines) on biomarker and multigene assay testing in ER positive, HER-2 negative breast carcinomas, with a focus on the four most relevant breast cancer biomarkers (ER, progesterone receptor (PR), HER-2, and Ki-67), the five most commonly discussed multigene assays (Oncotype DX®, MammaPrint®, Prosigna®, EndoPredict®, and Breast Cancer IndexTM), with a brief discussion on the emerging BluePrint® multigene assay. more...

Vascular lesions are uncommonly encountered in the breast and they represent a spectrum of benign, atypical and malignant entities. The mammary angiosarcomas can be primary arising de novo, or most frequently secondary to prior radiation therapy for breast carcinoma. There is significant overlap in pathologic features between vascular lesions and their non-vascular mimics, as well as between benign vascular lesions and their malignant counterparts, resulting in diagnostic dilemma, especially in the core biopsy setting. In this article, we review the clinico-radiological findings, pathologic features, role of ancillary testing as well as the management and prognosis of breast vascular lesions, with emphasis on essential pathologic features and potential diagnostic pitfalls. more...

Germline mutations in BRCA genes have been shown to predispose patients to breast cancer. Studies have suggested that p53 alteration is a necessary step in tumorigenesis in BRCA carriers. Our previous study showed p53 alteration in morphologically normal/benign breast luminal cells in sporadic breast cancer patients, the so-called breast p53 signature. Here, we studied p53 status in 66 BRCA1/2 carriers' breasts: 29 patients with breast carcinoma (2 patients with bilateral breast carcinomas) and 37 without. Seven of the 12 (58%) triple-negative breast carcinomas in BRCA carriers were positive for p53 alteration (immunohistochemical stain and/or sequencing), the same frequency as in sporadic triple-negative breast carcinomas. Focal p53 positivity in adjacent normal/benign luminal cells was identified in 4 of the 7 cases with p53-positive carcinomas but not in breasts with p53-negative carcinomas, indicating that p53 positivity in normal/benign breast luminal cells is not a random event. Furthermore, in BRCA carriers' prophylactic mastectomies, 12 of the 94 (12.77%) breasts had focal p53 positivity in normal/benign luminal cells, with 2 cases in bilateral breasts, significantly higher than in previously studied mammoplasty specimens (0%). Our study suggests that germline BRCA gene mutations could result in genomic instability and an elevated gene mutation rate (such as the p53 gene) in breast luminal cells compared with the general population, predisposing BRCA carriers to develop p53-positive/triple-negative breast carcinomas. more...

Summary p53 alterations have been identified in approximately 23% of breast carcinomas, particularly in hormone receptor–negative high-grade carcinomas. It is considered to be an early event in breast carcinogenesis. Nevertheless, the putative precursor lesion of high-grade breast carcinoma remains elusive. Breast excision specimens from 93 triple-negative high-grade invasive ductal carcinomas, 48 estrogen receptor (ER)–positive/progesterone receptor–positive/Her2-negative non–high-grade invasive ductal carcinomas, and 50 mammoplasty breasts were selected. At least 2 tissue blocks with tumor and adjacent benign tissue were sectioned and subjected to immunohistochemistry staining for p53. TP 53 gene sequencing was performed on select tumors. Further immunohistochemistry staining for ER and Ki-67 was performed on consecutive sections of tissue with p53-positive normal/benign cells. Of the 93 high-grade carcinomas, 51 (55%) were positive for p53 alteration, whereas only 3 (6.25%) of the 48 non–high-grade carcinomas were p53 altered. Focal p53 positivity in adjacent normal/benign breast tissue was identified in 19 cases, and 18 of them also had p53 alteration in their carcinomas. Only 1 case had focal p53 staining in normal/benign tissue, but the tumor was negative for p53 alteration. No p53 staining positivity was identified in the mammoplasty specimens. The p53-stained normal/benign cells were ER negative and did not show an increase in the Ki-67 labeling index. These findings indicate that the p53 staining positivity in normal/benign breast tissue is not a random event. It could be considered as the "p53 signature" in breast and serve as an indicator for future potential risk of p53-positive high-grade breast carcinoma. more...

Oncotype DX (Genomic Health, Redwood City, CA, USA, current list price $4,350.00) is a multigene quantitative reverse transcription-polymerase chain reaction-based assay that estimates the risk of distant recurrence and predicts chemotherapy benefit for patients with estrogen receptor (ER)-positive breast cancers. Studies have suggested that standard histologic variables can provide similar information. Klein and Dabbs et al have shown that Oncotype DX recurrence scores can be estimated by incorporating standard histologic variables into equations (Magee equations). Using a simple modification of the Magee equation, we predict the Oncotype DX recurrence score in an independent set of 283 cases. The Pearson correlation coefficient (r) for the Oncotype DX and average modified Magee recurrence scores was 0.6644 (n=283; P0.0001). 100% of cases with an average modified Magee recurrence score30 (n=8) or an average modified Magee recurrence score9 (with an available Ki-67, n=5) would have been correctly predicted to have a high or low Oncotype DX recurrence score, respectively. 86% (38/44) of cases with an average modified Magee recurrence score≤12, and 89% (34/38) of low grade tumors (NS6) with an ER and PR≥150, and a Ki-6710%, would have been correctly predicted to have a low Oncotype DX recurrence score. Using an algorithmic approach to eliminate high and low risk cases, between 5% and 23% of cases would potentially not have been sent by our institution for Oncotype DX testing, creating a potential cost savings between $56,550.00 and $282,750.00. The modified Magee recurrence score along with histologic criteria may be a cost-effective alternative to the Oncotype DX in risk stratifying certain breast cancer patients. The information needed is already generated by many pathology laboratories during the initial assessment of primary breast cancer, and the equations are free. more...

While efforts are made to improve tissue quality and control preanalytical variables, pathologists are often confronted with the challenge of molecular analysis of patient samples of unknown quality. Here we describe a first attempt to construct a tissue quality index (TQI) or an intrinsic control that would allow a global assessment of protein status based on quantitative measurement of a small number of selected, informative epitopes. Quantitative immunofluorescence (QIF) of a number of proteins was performed on a series of 93 breast cancer cases where levels of expression were assessed as a function of delayed time to formalin fixation. A TQI was constructed based on the combination of proteins that most accurately reflect increased and decreased levels of expression in proportion to delay time. The TQI, defined by combinations of measurements of cytokeratin, ERK1/2 and pHSP-27 and their relationship to cold ischemic time were validated on a second build of the training series and on two independent breast tissue cohorts with recorded time to formalin fixation. We show an association of negative TQI values (an indicator for loss of tissue quality) with increasing cold ischemic time on both validation cohorts and an association with loss of ER expression levels on all three breast cohorts. Using expression levels of three epitopes, we can begin to assess the likelihood of delayed time to fixation or decreased tissue quality. This TQI represents a proof of concept for the use of epitope expression to provide a mechanism for monitoring tissue quality. more...

The American Society of Clinical Oncology/College of American Pathologists ERBB2 testing guidelines address several pre-analytical variables known to affect ERBB2 testing accuracy. According to 2010 updated guidelines, the pre-analytical variable of time to tissue fixation (cold ischemia time) should be kept to1 h, however, little has been published about cold ischemia time and its significance in ERBB2 testing. To that end, this study evaluated ERBB2 status using two different FDA-approved in-situ hybridization methods and an FDA-approved immunohistochemistry (IHC) assay in the largest cohort to date (n=84) of invasive breast carcinomas with tracked cold ischemia time. Cold ischemia time was stratified into four groups (1 h (n=45), 1-2 h (n=27), 2-3 h (n=6), and3 h (n=6)) and ERBB2 status was evaluated in each group by IHC (4B5) and by in-situ hybridization methodologies (PathVysion(®) fluorescence in situ hybridization and the INFORM HER2(®) dual in situ DNA probe assay). Both in-situ hybridization methods were evaluated using three ERBB2 scoring criteria (dual-probe guidelines, single-probe guidelines, and the FDA package insert scoring instructions). Fluorescence in-situ hybridization (FISH) and INFORM HER2(®) demonstrated 100% concordance in the detection of ERBB2 amplification by all three scoring guidelines at all cold ischemia time points. Agreement between in-situ hybridization methodologies and IHC was superior using single-probe guidelines compared with dual probe or FDA scoring instructions. In addition, Inform HER2(®) in-situ hybridization signals were significantly more intense than FISH at all cold ischemia time points, however, no significant loss of either chromosome 17 or ERBB2 signal was detected by FISH or Inform HER2(®) in-situ hybridization in cold ischemia times up to 3 h. On the basis of our findings, cold ischemia time up to 3 h has no deleterious effect on the detection of ERBB2 via in-situ hybridization or IHC. more...

Advanced breast cancers preferentially metastasize to bone where cells in the bone microenvironment produce factors that enhance breast cancer cell homing and growth. Expression of the ubiquitin E3 ligase WWP1 is increased in some breast cancers, but its role in bone metastasis has not been investigated. Here, we studied the effects of WWP1 and itch, its closest family member, on breast cancer bone metastasis. First, we immunostained a multi-tumor tissue microarray and a breast cancer tissue microarray and demonstrated that WWP1 and ITCH are expressed in some of breast cancer cases. We then knocked down WWP1 or itch in MDA-MB-231 breast cancer cells using shRNA and inoculated these cells and control cells into the left ventricle of athymic nude mice. Radiographs showed that mice given shWWP1 cells had more osteolytic lesions than mice given control MDA-MB-231 cells. Histologic analysis confirmed osteolysis and showed significantly increased tumor area in bone marrow of the mice. WWP1 knockdown did not affect cell growth, survival or osteoclastogenic potential, but markedly increased cell migration toward a CXCL12 gradient in vitro. Furthermore, WWP1 knockdown significantly reduced CXCL12-induced CXCR4 lysosomal trafficking and degradation. In contrast, itch knockdown had no effect on MDA-MB-231 cell bone metastasis. Taken together, these findings demonstrate that WWP1 negatively regulates cell migration to CXCL12 by limiting CXCR4 degradation to promote breast cancer metastasis to bone and highlight the potential utility of WWP1 as a prognostic indicator for breast cancer bone metastasis. more...

This article takes the form of a personal reflection on the struggle to establish futures education in the UK school curriculum. After promising beginnings in the 1980s under the aegis of global educators the 1990s saw a retrenchment in order to create a research base and to develop appropriate support materials for teachers. Whilst until recently not understood or accepted by most mainstream educators a futures perspective is now beginning to be included in the work of geographical educators. In particular some aspects of futures thinking are also becoming enshrined in initiatives relating to education for sustainability. Encouraging teachers to develop a futures perspective in their own curriculum area may be a more profitable way forward than trying to promote futures education as a separate entity. Dominant neoliberal ideology and its influence on education will always make it difficult to challenge mainstream views of the future. more...

Giant cell tumor of the salivary gland is extremely rare, with only 15 cases published in the English literature. The tumor characteristically contains a mixture of multinucleated giant cells, resembling osteoclasts of bone, and neoplastic mononuclear cells. In about half of the reported cases, there is an associated carcinomatous component. We are reporting an additional case of giant cell tumor of the parotid gland that was initially misinterpreted as an extraosseous osteosarcoma in the biopsy specimen. The histologic and immunohistochemical findings as well as a review of the literature with discussion of the histogenesis of this unusual neoplasm are presented. more...

That metastatic tumor cells grow in selective non-native environments suggests an ability to differentially respond to local microenvironments. BRMS1, like other metastasis suppressors, halts ectopic growth (metastasis) without blocking orthotopic tumor formation. BRMS1-expressing tumor cells reach secondary sites but do not colonize distant tissues, compelling the hypothesis that BRMS1 selectively restricts the ability of tumor cells to respond to exogenous regulators in different tissues. Here we report that BRMS1 expression in metastatic human breast cancer cells leads to a selective reduction in epidermal growth factor receptor expression and downstream (AKT) signaling. Signaling through another receptor tyrosine kinase, hepatocyte growth factor receptor (c-Met), remains unaltered despite reduced levels of the signaling intermediate phosphatidylinositol (4,5)-bisphosphate. Interestingly, reduced downstream calcium signaling is observed following treatment with platelet-derived growth factor, consistent with decreased phosphatidylinositol (4,5)-bisphosphate. However, platelet-derived growth factor receptor expression is unaltered. Thus, BRMS1 differentially attenuates cellular responses to mitogenic signals, not only dependent upon the specific signal received, but at varying steps within the same signaling cascade. Specific modulation of signaling responses received from the microenvironment may ultimately dictate which environments are permissive/restrictive for tumor cell growth and provide insights into the biology underlying metastasis. more...

The expression of WAVE3, an actin-cytoskeleton and reorganization protein, is elevated in malignant human breast cancer, yet the role of WAVE3 in promoting tumor progression remains undefined. We have recently shown that knockdown of WAVE3 expression in human breast adenocarcinoma MDA-MB-231 cells using small interfering RNA resulted in a significant reduction of cell motility, migration, and invasion, which correlated with a reduction in the levels of active p38 mitogen-activated protein kinase. Here, we investigated the effect of stable suppression of WAVE3 by short hairpin RNA on tumor growth and metastasis in xenograft models. Breast cancer MDA-MB-231 cells expressing short hairpin RNA to WAVE3 (shWAVE3) showed a significant reduction in Matrigel invasion and formation of lung colonies after tail-vein injection in SCID mice. In the orthotopic model, we observed a reduction in growth rate of the primary tumors, as well as in the metastases to the lungs. We also show that suppression of p38 mitogen-activated protein kinase activity by dominant-negative p38 results in comparable phenotypes to the knockdown of WAVE3. These studies provide direct evidence that the WAVE3-p38 pathway contributes to breast cancer progression and metastasis. more...

This article begins by noting some of the global concerns that young people have today and highlights the crucial role of global education in responding to such concerns. It then considers the importance of teacher training in such matters and reports on a preliminary study relating to the initial training of teachers in England. In particular this raises questions about the knowledge and understanding that such students bring to their courses. It concludes by identifying some of the consequent dilemmas faced by teacher trainers working in this context. more...

The analysis of gene expression by growth plate chondrocytes in vivo has been hampered by the inherent difficulty in performing in situ hybridization on mineralized tissues. The combination of laser capture microdissection and reverse transcription-polymerase chain reaction (RT-PCR) allows analysis of gene expression by cells selectively removed from histologic sections by laser ablation. In order to apply this method to mineralized tissues, a decalcification process is required. The object of this study was to determine the optimal method for tissue decalcification prior to laser capture microdissection RT-PCR that will preserve integrity of the mRNA population. Acetone, 10% formalin, and methacarn were evaluated as fixatives, while Surgipath Decalicifier I, 10% ethylenediaminetetraacetic acid (EDTA), and 20% EDTA were evaluated as decalcifying reagents. Our results demonstrate that the optimal RNA quality was preserved by a decalcification protocol consisting of 20% EDTA for decalcification followed by fixation in methacarn, although this method is also associated with a reduction in RNA quantity. more...

Chondrosarcomas are the second most common primary malignant tumor of bone. Chemotherapy for conventional chondrosarcomas is generally ineffective. Methylthioadenosine phosphorylase (MTAP) is a ubiquitous enzyme, essential in the salvage pathway of adenine and in methionine synthesis. MTAP-deficient cells are more susceptible than wild-type cells to pharmacologic inhibitors of de novo purine synthesis. Homozygous deletions of MTAP have been reported in hematologic and solid tumor malignancies. Based on these observations, we investigated the frequency of MTAP deletions in conventional, grade II chondrosarcomas by fluorescence in situ hybridization (FISH) analysis: 23 conventional, grade II chondrosarcoma patient samples from the Cleveland Clinic Foundation were analyzed for MTAP deletions. Nuclei were successfully extracted from 14 of 23 samples (61% evaluable) for FISH analysis: 7 of 14 samples (50%) showed either homozygous or hemizygous deletion of the MTAP gene, 6 of 14 (43%) failed to show deletion, and 1 of 14 (7%) was inconclusive. These findings suggest that approximately one-half of conventional, grade II chondrosarcomas may be preferentially sensitive to pharmacologic inhibitors of de novo purine synthesis. The present study led to development by the Intergroup Coalition Against Sarcomas of a phase II trial of pemetrexed, a multitargeted anti-folate, for advanced chondrosarcomas. more...

Microphthalmia-associated transcription factor (Mitf), a member of the helix-loop-helix transcription factor subfamily, normally expressed in mononuclear and multinucleated osteoclasts, is involved in the terminal differentiation of osteoclasts. Dysfunction of osteoclast activity resulting from abnormal Mitf expression has been implicated in osteopetrosis. Numerous other giant cells of various types including osteoclast-like giant cells seen in various tumors, traditionally thought to be monocyte derived, are seen in a variety of bone and extraosseous lesions. Using a monoclonal antibody with a standard immunohistochemical technique on paraffin sections, we evaluated expression of Mitf in 89 various giant cell lesions including giant cell tumor of bone (n26), giant cell tumor of tendon sheath/pigmented villonodular synovitis (n24), giant cell reparative granuloma (n3), aneurysmal bone cysts (n11), chondroblastomas (n7), foreign body giant cell reaction (n10), and sarcoidosis (n8). We also evaluated three cases of osteopetrosis and 27 various tissues without monocyte-derived giant cells (nine bone marrows, nine products of conception, seven lymph nodes with sinus histiocytosis, one granulation tissue and one thymus). Nuclear Mitf immunoreactivity was evaluated. Mitf was variably expressed in the monocyte-derived giant cells and/or the adjacent mononuclear cells/histiocytes in 23 (89%) giant cell tumors of the bone, 23 (96%) giant cell tumors of tendon sheath/pigmented villonodular synovitis, three (100%) giant cell reparative granuloma, eight (73%) aneurysmal bone cysts, five (71%) chondroblastomas, eight (80%) foreign-body giant cell reactions, and six (75%) sarcoidoses. No Mitf immunoreactivity was detected in cases of osteopetrosis and giant cells of nonmonocyte origin. Mitf immunoreactivity is rare in tissues with rich mononuclear cells/histiocytes but no monocyte derived giant cells. These findings support the notion that giant cells in giant cell lesions are likely derived from adjacent mononuclear cells and Mitf might play a role in the multinucleation process of such cells. more...

Periods of rapid and turbulent change affect societies in a variety of ways including, in the 1990s, a reawakening of interest in millenarian themes. This paper reviews some key elements of the millennial tradition and then notes that little serious attention has been paid to public perceptions of the year 2000. Secondly the paper reports on an experiential research project in which participants explored what meanings the twentieth century, the millennium, and the new century held for them. In investigating their histories and hopes they found that the personal and the political were inextricably interrelated and that the stories they shared of past, present and future led them back to the deeper perennial questions of human existence. more...

Eighteen cadaver hands were studied to investigate the relationship between degeneration of the palmar beak ligament and articular disease of the trapeziometacarpal joint. Eight of 18 joints had chondromalacia alone; 10 contained areas of eburnation in the palmar aspect of the joint. Beak ligament degeneration correlated closely with the presence of articular degeneration; all joints with eburnation demonstrated frank detachment of the ligament from its metacarpal insertion site. Histologically, the collagen fibers of the beak ligament were disorganized at the metacarpal attachment. The normal insertional zone of fibrocartilage was often unrecognizable on the metacarpal side and, in more degenerative specimens, an intervening synovial recess appeared at the palmar beak of the metacarpal. The trapezial insertion of the beak ligament showed no degenerative change. Increasingly severe cartilage disease was associated with progressive and selective degeneration of the collagen framework of the beak ligament at its insertion onto the thumb metacarpal. These localized histopathologic findings further support the existence of an anatomically distinct intra-articular beak ligament essential to the normal function of the trapeziometacarpal joint and suggest an etiologic relationship to osteoarthritic disease. (J Hand Surg 1999;24A:496–504. Copyright © 1999 by the American Society for Surgery of the Hand.) more...

This paper reports on a research project which facilitated a group of socially committed educators to clarify the nature of their desirable futures and to identify their sources of hope. This work is set within the normative tradition of futures studies and an account is given of how the research process was arrived at and the way in which people responded to this. A participatory and experiential focus group format enabled participants to explore these issues in a fruitful and synergetic way. Key elements of their preferable futures and primary sources of hope are identified and then compared with previous research findings. Finally these concerns are located within wider contemporary debates about revisionary postmodernism, sustainable futures and the utopian tradition. more...

This article explores the importance of recent and current research into popular images of the future. It begins by reviewing the main literature on adults' and young people's views of the future and then goes on to describe the findings of a recent UK research project. This examined how 7–18-year-olds see the future at personal, local and global scales. The responses of different age groups are examined as well as variations based on gender. Finally, the significance and importance of this research for futurists and educators are emphasized. more...

We performed tetracycline double-labeled bone biopsies and serial bone densitometry on four patients with anorexia nervosa to determine the effects of various conditions of sex hormone replacement and body weight status. We found negligible bone mineral apposition rate in two patients with anorexia nervosa who were taking estrogen and progestin pills while weighing only 79% of normal. However, bone mineral apposition rate was normal in two patients with anorexia nervosa who took no sex hormones and remained amenorrheic while weighing 87% of normal. Histomorphometric analysis revealed a decrease in intracortical trabecular area by 57% and an increase in active osteoblastic surface area by 300%, comparing the subjects who were taking hormone replacement to those who were not. There was no direct evidence of increased resorption in any subject. Six months after biopsy, the two subjects taking sex hormones decreased lumbar bone mineral density by 1.9%, while the two taking no sex hormones remained amenorrheic, but increased bone mineral density by 1.3%. Therefore, we propose that sex hormone therapy in the presence of persistently low body weight might be of limited benefit for bone mineral apposition and density. more...

The purpose of this study was to investigate the possibility of iatrogenically creating disc displacement in the human temporomandibular joint (TMJ). Fourteen fresh TMJ autopsy specimens with superior disc position were selected for the study. The upper and lower joint spaces were exposed via a preauricular incision and two to three superficial mediolateral incisions were made in the inferior surface of the posterior disc attachment (ie, retrodiscal tissue). After these incisions were made it was possible to manually displace the disc anteriorly. To maintain the disc in the anterior position the condyle was positioned against the posterior disc attachment in a manner corresponding to the closed mouth position. The joints were then fixed in this relationship and magnetic resonance imaging (MRI) was repeated using the same scanning plane and scanning parameters as before intervention. After imaging, the joints were cryosectioned to show the degree of disc displacement. Histologic analysis was made of the posterior disc attachment. Postoperative MR images and cryosections showed the disc to be displaced anteriorly in 12 of the 14 joints. Displacement of the disc was complete in eight joints (the entire mediolateral dimension of the joint) and partial (only in the lateral part of the joint) in four joints. The disc remained in a superior position in two joints. Cryosections and histologic analysis showed the incisions in the inferior aspect of the posterior disc attachment to be superficial. The results of this study suggest that the integrity of the inferior aspect of the posterior attachment of the disc to the condyle is essential for keeping the disc in its position superior to the condyle.(ABSTRACT TRUNCATED AT 250 WORDS) more...

To document a causal relationship between temporomandibular joint disk displacement and arthrosis, the disk was surgically displaced in one temporomandibular joint in each of three rabbits. The rabbits were sacrificed after 4 weeks and the mandibular condyles were studied radiographically and histologically. All three joints that underwent disk displacement had radiographic and histologic evidence of arthrosis, which included erosion of the bone, irregularity and fissure formation of the articular soft tissue cover, disruption of the subchondral layer of cartilage cells, and chondrocyte proliferation. No radiographic or histologic changes occured in the joints that were untouched. The results suggest that surgically created disk displacement can cause arthrosis in the temporomandibular joint of the rabbit. more...

Hyperostosis cranii ex vacuo is a condition that may develop after successful ventricular shunting for hydrocephalus. It is characterized by diffuse thickening of the skull (particularly the inner table) involving the calvarium and the base. It is a diagnosis that distinguishes marked calvarial thickening from thickening of the skull because of other causes. It is an entity that needs to be considered in patients who have diffuse thickening of the skull, have premature closure of sutures, and who have been treated for hydrocephalus in the past. more...

Two-dimensional echo patterns (EP) of 21 pathologically confirmed intra-cardiac masses (10 tumors, 6 thrombi and 5 vegetations) were correlated with histopathology. Three types of echo patterns were defined. Five tumors and 3 thrombi demonstrated a fine, speckled and uniform appearance (type AEP) and none had any hemorrhages or calcification on pathological examination. Three left atrial masses showed large and discrete echolucent areas (type B EP) and histopathological correlation revealed large hemorrhages in the tumors and a large area of clot lysis in the thrombus. Three tumors, 2 thrombi and 5 vegetations revealed either localized areas of bright echoes or appeared uniformly bright (type C EP) and on pathological examination, all had calcification and/or fibrosis. Two-dimensional echo patterns are useful in delineating some of the structural components of intracardiac masses. more...