Application of breast cancer risk prediction models in clinical practice.

Breast cancer risk assessment provides an estimation of disease risk that can be used to guide management for women at all levels of risk. In addition, the likelihood that breast cancer risk is due to specific genetic susceptibility (such as BRCA1 or BRCA2 mutations) can be determined. Recent developments have reinforced the clinical importance of breast cancer risk assessment. Tamoxifen chemoprevention as well as prevention studies such as the Study of Tamoxifen and Raloxifene are available to women at increased risk of developing breast cancer. In addition, specific management strategies are now defined for BRCA1 and BRCA2 mutation carriers. Risk may be assessed as the likelihood of developing breast cancer (using risk assessment models) or as the likelihood of detecting a BRCA1 or BRCA2 mutation (using prior probability models). Each of the models has advantages and disadvantages, and all need to be interpreted in context. We review available risk assessment tools and discuss their application. As illustrated by clinical examples, optimal counseling may require the use of several models, as well as clinical judgment, to provide the most accurate and useful information to women and their families.     

Malignant fibrous histiocytoma in the area of the head and neck]

Although malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adult life, it is fairly rare in the head and neck region (3-6%). Between 1983 and 1991 8 patients with MFH in the head and neck region have been observed and treated at the ENT-department of the University of Tübingen. 5 patients have been operated (laryngopharyngeal localization), 2 patients underwent irradiation (unresectable fast growing T4-tumors of the pharynx and thyroid) and one female patient refused further therapy after two resections elsewhere. Operated patients showed no evidence of disease 2-8 years after resection (all margins have been controlled histologically). Both irradiated patients died 4 respectively 2 months after full (70 Gy) and incomplete (17 Gy) radiotherapy without visible positive effects. Both patients developed pulmonary metastasis. Since MFH can grow in thin layers along musculaoponeurotic structures the exact size is not always demonstrable by ultrasound, CT or MR scans. Metastasis occur in up to 40%, preferentially in regionary lymph nodes, in lung, liver and skeletal system. These phenomenon requires a full pretherapeutic staging. Histologically MFH is sometimes hard to distinguish from other tumors as for example various sarcomas and pleomorphic carcinoma. Therefore, immunohistochemical (mesenchymal markers) and electron microscopical investigations are advised. Resection with exact histological controll of all margins is the therapy of choice. We experienced that laryngeal MFH (n = 3) can be resected without laryngectomy under certain circumstances. Although unsuccessfull in our two cases, according to the literature, radiotherapy should be administered in unresectable cases. Depending on localization and size of MFH long survival, in single cases healing, of this disease is possible by surgical treatment.     

PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (I)

Occupational diseases Nos. 2108 and 2110 correspond to intervertebral disc-related diseases of the lumbar spine from many years of carrying or lifting heavy loads, occupations in extreme postures of full flexion or oscillation of the whole body when seated, and which compel the cessation of all activities which are or could be the cause for the origin, exacerbation or recurrence of the disease. These occupational diseases came into force at the start of 1993, but there have been considerable problems in their implementation. The present Part I of the contribution is the result of the work of an interdisciplinary study group and contains medical criteria for the assessment of possibly strain-related clinical characteristics and the evaluation of other possible causes. Part II is to be published in Volume 4/2005 and will deal with questions related to forced cessation and to the assessment of the loss of earning ability. Agreement was reached in many areas related to the assessment of occupational claims. This should allow for evidence-based decision making in the future for the occupational diseases Nos. 2108 and 2110.     

Working memory after severe traumatic brain injury.

The aim of the present study was to assess the functioning of the different subsystems of working memory after severe traumatic brain injury (TBI). A total of 30 patients with severe chronic TBI and 28 controls received a comprehensive assessment of working memory addressing the phonological loop (forward and backward digit span; word length and phonological similarity effects), the visuospatial sketchpad (forward and backward visual spans), and the central executive (tasks requiring simultaneous storage and processing of information, dual-task processing, working memory updating). Results showed that there were only marginal group differences regarding the functioning of the two slave systems, whereas patients with severe TBI performed significantly poorer than controls on most central executive tasks, particularly on those requiring a high level of controlled processing. These results suggest that severe TBI is associated with an impairment of executive aspects of working memory. The anatomic substrate of this impairment remains to be elucidated. It might be related to a defective activation of a distributed network, including the dorsolateral prefrontal cortex.     

BUILDING THE FOUNDATION OF EXCELLENCE IN HEART FAILURE NURSING

This column contains the presidential address presented during the Third Annual Meeting of the American Association of Heart Failure Nurses on June 28, 2007, in San Diego, California, titled "Building the Foundation of Excellence in Heart Failure Nursing."