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.     

The everyday realities of the multi-dimensional role of the high school community nurse.

The traditional role of the high school based community community health nurse has changed considerably over recent decades. This article describes a qualitative study, in which nine community health nurses from eight different high schools completed a diary of the interventions and events during the course of two working days in order to identify the dimensions of their role. A short demographic questionnaire was also completed by the nurses and included two open-ended questions concerning their main professional issues and concerns. The researchers sought verification of the interpretation of the data through a focus group interview with the high school nurses. Data analysis indicated that the role of the high school community health nurses (CHN) consisted of seven categories. These were provider of clinical care, counsellor/ mediator, advocacy and support, liaison/referral, health promotion/education and resource agent, and professional management and research role. The findings highlight the complex and demanding aspects of the role of the high school nurse and articulate the importance of describing the contribution of such practitioners in to the promotion of health among adolescents.     

CAR2 displays unique ligand binding and RXRalpha heterodimerization characteristics.

The constitutive androstane receptor (CAR; NR1I3) regulates the expression of genes involved in xenobiotic metabolism. Alternative splicing of the human CAR gene yields an array of mRNAs that encode structurally diverse proteins. One form of CAR, termed CAR2, contains an additional four amino acids (SPTV) that are predicted to reshape the ligand-binding pocket. The current studies show a marked, ligand-independent, CAR2-mediated transactivation of reporters containing optimal DR-3, DR-4, and DR-5 response elements, and reporters derived from the natural CYP2B6 and CYP3A4 gene promoters. Overexpression of the RXRalpha ligand binding domain was critical for achieving these effects. CAR2 interaction with SRC-1 was similarly dependent on the coexpression of RXRalpha. Mutagenesis of Ser233 (SPTV) to an alanine residue yielded a receptor possessing higher constitutive activity. Alternatively, mutating Ser233 to an aspartate residue drastically reduced the transactivation capacity of CAR2. The respective abilities of these mutagenized forms of CAR2 to transactivate a DR-4 x 3 reporter element correlated with their ability to interact with RxRalpha and to recruit SRC-1 in a ligand-regulated manner. Together, these results demonstrate a robust RXRalpha-dependent recruitment of coactivators and transactivation by CAR2. In addition, CAR2 displays novel dose responses to clotrimazole and androstanol compared with the reference form of the receptor while at the same time retaining the ability to bind CITCO. This result supports a hypothesis whereby the four-amino-acid insertion in CAR2 structurally modifies its ligand binding pocket, suggesting that CAR2 is regulated by a set of ligands distinct from those governing the activity of reference CAR.     

Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

Table 1     

Serum ferritin in haemodialysis patients: is there a relationship to 'haemochromatosis alleles' HLA A3, B7, B14?

Serum ferritin levels were measured in 57 patients on maintenance haemodialysis to determine if patients who possessed 1 or more of the histocompatibility antigens associated with idiopathic haemochromatosis (HLA A3, B7 or B14) were at increased risk of iron overload. There was no significant difference in the mean serum ferritin levels between those patients with HLA A3, B7 or B14 (357.9 +/- 522.6 ng/1; n = 19) and those without these antigens (393.7 + 556.2 ng/1; n = 38). Iron overload in haemodialysis patients is not a histocompatibility-linked disorder.     

Relocation mortality in dementia: The effects of a new hospital

Relocation mortality has been cited as an important factor when considering the placement of elderly patients. This study describes the fate of dementia patients relocated to facilitate the move to a new hospital. Some wards were moved as intact units—that is, the patients were kept together and there was little change in the nursing or medical staff. Two other wards were closed, and these patients were dispersed to several existing and new wards and experienced changes of nursing and medical staff. All patients underwent prerelocation and postrelocation orientation programmes. The mortality figures for the total patient group before and after the relocation do not show any statistically significant increase in mortality postrelocation. However, for wards that were closed and where the patients suffered maximum disruption to patient group and nursing staff, there was a significant increase in mortality rates.     

Geographic Benefit from Decentralized Medical Education: Student and Preceptor Practice Patterns

The performance of area health education center (AHEC)-stimulated programs and decentralized education for medicine is not well understood. The Statewide Education Activities for Rural Colorado's Health (SEARCH)/AHEC project at the University of Colorado School of Medicine was examined to determine if the program had an effect on the practice location of its graduates. Practice location and specialty of graduates of the University of Colorado School of Medicine (UCSOM) classes 1980-1985 were compared for students who had participated in decentralized SEARCH/AHEC experiences versus students who had not. The majority of the graduates were practicing out of state in 1990. Non-Colorado doctors were more often practicing in rural (non-metropolitan statistical area [MSA]) counties and in towns of fewer than 2,500, 5,000 and 10,000 residents, respectively. In addition, of the 251 active patient care physicians practicing in Colorado communities of fewer than 10,000 in non-MSA counties in 1986, those who precepted UCSOM students on SEARCH rotations were more likely to have remained in their same practice location in 1992 (77.8% versus 62.1% for those who had not precepted students). This analysis of both student and preceptor practice patterns documents the value of decentralized medical education in addressing the geographic and specialty maldistribution of physicians. These results have important policy implications for funding medical education programs.     

The AMPA receptor potentiator LY404187 increases cerebral glucose utilization and c-fos expression in the rat.

AMPA receptor potentiators enhance AMPA receptor-mediated glutamatergic neurotransmission and may have therapeutic potential as cognitive enhancers or antidepressants. The anatomical basis for the action of AMPA receptor potentiators is unknown. The aim of this study was to determine the effects of the biarylpropylsulfonamide AMPA receptor potentiator, LY404187 (0.05 to 5 mg/kg subcutaneously), upon cerebral glucose utilization and c-fos expression using 14C-2-deoxglucose autoradiography and c-fos immunocytochemistry. LY404187 (0.5 mg/kg) produced significant elevations in glucose utilization in 28 of the 52 anatomical regions analyzed, which included rostral neocortical areas and the hippocampus, as well the dorsal raphe nucleus, lateral habenula, and locus coeruleus. No significant decreases in glucose utilization were observed in any region after LY404187 administration. The increases in glucose utilization with LY404187 (0.5 mg/kg) were blocked by pretreatment with the AMPA receptor antagonist LY293558 (25 mg/kg), indicating that LY404187 acts through AMPA receptor-mediated mechanisms. LY404187 (0.5 mg/kg) also produced increases in c-fos immunoreactivity in the cortex, locus coeruleus, and the dorsal raphe nucleus. These studies demonstrate neuronal activation in key brain areas that are associated with memory processes and thus provide an anatomical basis for the cognitive enhancing effects of AMPA receptor potentiators.