Distinction between dysplasia-associated lesion or mass (DALM) and adenoma in patients with ulcerative colitis

Polyps with epithelial dysplasia in ulcerative colitis (UC) represent either dysplasia-associated lesions or masses (DALMs) or sporadic adenomas. DALMs are frequently associated with associated carcinoma and are an indication for colectomy. Removal of the polyp is treatment of choice for sporadic adenomas. Differentiating between these 2 lesions is not always easy. The goal of this study was to distinguish DALMs from adenomas in patients with UC on a genetic basis. We evaluated genetic alterations in DALMs and compared them with a previously published set of dysplastic polyps in patients with UC that were considered adenomas for the following reasons: (1) polyps were located outside of current active disease; (2) polyps had histological features of sporadic adenomas; and (3) patients displayed a uneventful follow-up after polypectomy (UC-adenomas). In addition, adenomas not associated with UC were studied. Genetic alterations on chromosome 3p were assessed for the markers D3S1766, D3S2409, and D3S2387. LOH with or without microsatellite instability was found in 70%, 37%, and 57% of cases of DALM, respectively. In contrast, UC-adenomas lesions exhibited genetic alterations in 8.3%, 11.7%, and 15.3% for the respective markers. Spontaneous adenomas exhibited genetic alterations in 10.5%, 7.1%, and 0% of cases, which were not significantly different from the UC-adenoma results. These results indicate that UC-adenomas are genetically and biologically similar to sporadic adenomas and that UC-adenomas may biologically represent sporadic adenomas, supporting on a genetic basis the criteria chosen to diagnose adenomas in UC. Genetic markers on chromosome 3p may be useful in the differential diagnosis between DALM and UC-adenomas.     

Nurses' perceived barriers to the implementation of a Fall Prevention Clinical Practice Guideline in Singapore hospitals

Background  

Theories of behavior change indicate that an analysis of barriers to change is helpful when trying to influence professional practice. The aim of this study was to assess the perceived barriers to practice change by eliciting nurses' opinions with regard to barriers to, and facilitators of, implementation of a Fall Prevention clinical practice guideline in five acute care hospitals in Singapore.     

Apoptosis and p53 in inverting papilloma of the sinonasal tract

The objective of this study was to identify apoptotic bodies and p53 positivity in inverting papilloma lesions to study these two as biomarkers in premalignant lesions. Archival specimens of 15 patients with inverting papilloma between the years 1992 and 1995 were retrieved. In situ end labeling technique was used to identify apoptotic bodies. Immunohistochemistry was used to detect p53 in the same specimens. The clinical course was evaluated conducting a retrospective chart review in these patients. Compared to normal epithelium, inverting papilloma lesions had a greater proportion of apoptotic bodies, which was nearly statistically significant (average 0.506/100 cells for inverting papilloma compared with 0.1/100 cells for the normal surrounding tissue). Four cases of inverting papilloma were p53 positive. There was, however, no association between p53 positive staining and the apoptotic rate. The minimum follow-up for patients was 2 years. All had a uniformly good clinical outcome with only one patient who was p53 positive showing concurrent squamous cell carcinoma. We concluded that inverting papilloma contained a higher average number of apoptotic bodies compared with normal surrounding sinonasal tissue. This showed a trend toward a positive between the apoptotic rate and premalignancy, suggesting both increased cellular proliferation and increased cell death may occur in such lesions. In this study p53 did not show a positive association with the apoptotic rate, suggesting that p53 may not be directly involved in the apoptotic regulatory pathway in inverting papillomas.     

Promotion of mammary cancer development by tamoxifen in a mouse model of Brca1-mutation-related breast cancer

Loss of full-length Brca1 in mammary epithelial cells of the mouse mammary tumor virus (MMTV)-Cre Brca1 conditional exon 11 deletion mouse model results in the development of mammary adenocarcinomas with similar genetic changes to those found in human BRCA1-mutation-related breast cancers. We used this experimental model to evaluate the chemopreventive effect of tamoxifen on the development of mammary preneoplasia and adenocarcinoma. No protective effects of tamoxifen administration on mammary cancer development were found. Instead, tamoxifen treatment significantly increased rates of mammary epithelial cell proliferation and the prevalence of mammary hyperplasia at 6 months of age. Tamoxifen-exposed mice developed adenocarcinomas at younger ages than control mice and a higher percentage of mice developed adenocarcinomas by 12 months of age. Both whole mouse and tissue culture cell models were used to test if loss of full-length Brca1 was associated with a relative increase in the agonist activity of tamoxifen. Tamoxifen induced increased ductal growth in MMTV-Cre Brca1 conditional mice compared to wild type. Estrogen receptor alpha (ERalpha) expression was downregulated in the tamoxifen-induced hyperplasias. Reducing BRCA1 levels in MCF-7 cells using siRNA resulted in a relative increase in the agonist activity of tamoxifen. Results suggest a model of mammary cancer progression in which loss of full-length Brca1 altered the agonist/antagonist activity of tamoxifen, resulting in tamoxifen-induced mammary epithelial cell proliferation with subsequent loss of ERalpha expression and development of ERalpha-negative hyperplasias and adenocarcinomas.     

Academic and behavioral limitations and health-related quality of life in school-age survivors of bacterial meningitis

The objectives of this study were to describe health-related quality of life of postmeningitic children and to examine the association between academic and/or behavioral limitations and health-related quality of life. One hundred and eighty-two children (mean age 9.7 years; range 5.3–14.2) were selected randomly from a cohort of 674 school-age children who recovered from non-Haemophilus influenzae type B bacterial meningitis. These children had neither meningitis with ‘complex onset’, nor prior cognitive or behavioral problems, nor severe disease sequelae. On average 7.4 years after meningitis, they were evaluated using an ‘Academic Achievement Test’ and their parents filled in the Child Behavior Checklist, the Child Health Questionnaire, and the Health Utilities Index. The long-term incidence of academic and/or behavioral limitations was 32%. Overall health-related quality of life of the postmeningitic children was decreased in comparison with that of a reference population of schoolchildren. The group of postmeningitic children with academic and/or behavioral limitations showed the most marked decrease in quality of life, especially concerning psychosocial health, cognition and family life. The negative effects on quality of life were not significantly influenced by age, gender, causative pathogen, presence of minor neurological impairment, or presence of hearing impairment. In conclusion, health-related quality of life of postmeningitic children is decreased, particularly of those with academic and/or behavioral limitations.     

Synthesis of alpha 1-anti-trypsin by human monocytes

The present report concerns the site of synthesis of alpha 1-anti-trypsin (alpha 1 AT). In this study circulating cells and tissue fragments were incubated with radioactive amino acids to be incorporated during protein synthesis. The de novo synthesis of proteins was demonstrated by autoradiography of the immunoelectrophoretic slide. The results constitute proof that alpha 1 AT is formed by circulating human monocytes and support those obtained in earlier immunofluorescent studies which showed that alpha 1 AT is present in pulmonary macrophages, as could be expected because these cells derive from circulating monocytes. The culture fluid of liver tissues also showed labelled alpha 1 AT, but it is not clear whether in this organ alpha 1 AT is formed by Kupffer cells and/or parenchymal cells.