Neuropathologic, biochemical, and molecular characterization of the frontotemporal dementias

The frontotemporal dementias (FTDs) are a heterogeneous group of neurodegenerative disorders that are characterized clinically by dementia, personality changes, language impairment, and occasionally extrapyramidal movement disorders. Historically, the diagnosis and classification of FTDs has been fraught with difficulties, especially with regard to establishing a consensus on the neuropathologic diagnosis. Recently, an international group of scientists participated in a consensus conference to develop such neuropathologic criteria. They recommended a diagnostic classification scheme that incorporated a biochemical analysis of the insoluble tau isoform composition, as well as ubiquitin immunohistochemistry. The use and reliability of this classification system has yet to be examined. In this study, we evaluated 21 cases of FTD. Using traditional histochemical stains and tau protein and ubiquitin immunohistochemistry, we separated each case into one of the following categories: classic Pick disease (PiD; n = 7), corticobasal degeneration (CBD; n = 5), dementia lacking distinctive histopathologic features (DLDH; n = 4), progressive supranuclear palsy (PSP; n = 2), frontotemporal lobar degeneration with motor neuron disease or motor neuron disease-type inclusions (FTLD-MND/MNI; n = 2), and neurofibrillary tangle dementia (NFTD; n = 1). Additionally, we independently categorized each case by the insoluble tau isoform pattern, including 3R (n = 5), 4R (n = 7), 3R/4R (n = 3), and no insoluble tau (n = 6). As suggested by the proposed diagnostic scheme, we found that the insoluble tau isoform patterns correlated strongly with the independently derived histopathologic diagnoses (p < 0.001). The data show that cases containing predominantly 3R tau were classic PiD (100%). Cases with predominantly 4R tau were either CBD (71%) or PSP (29%). Cases with both 3R and 4R tau were either a combination of PiD and Alzheimer disease (67%) or NFTD (33%). Finally, cases with no insoluble tau were either DLDH (67%) or FTLD-MND/MNI (33%). To further characterize these cases, we also performed quantitative Western blots for soluble tau, APOE genotyping, and, in selected cases, tau gene sequencing. We show that soluble tau is reduced in DLDH and FTLD-MND/MNI and that APOE4 is overrepresented in PiD and DLDH. We also identified a new family with the R406W mutation and pathology consistent with NFTD. This study validates the recently proposed diagnostic criteria and forms a framework for further refinement of this classification scheme.     

Associations between aerobic fitness and estrogen metabolites in premenopausal women

Chronic physical activity may alter estrogen metabolism, a proposed biomarker of breast cancer risk, by causing a shift toward higher 2-OHE1 and lower 16alpha-OHE1 levels. PURPOSE: To investigate the association between an objective indicator of chronic exercise, aerobic fitness, and 2-OHE1 and 16alpha-OHE1 in premenopausal women. METHODS: Women with high aerobic fitness (N=17; VO2max>or=48 mL.kg.min-1) were compared with women with average aerobic fitness (N=13; VO2max相似文献   

Complications of mandibular molar replacement with a single implant: a case report

This case report describes prosthodontic complications resulting from the surgical placement of a single implant and treatment following these complications. Both the surgical and prosthodontic procedures are described for the treatment of a 57-year-old man who had previously received a single implant for the replacement of a missing molar. Using 2 implants, 1 mesial and 1 distal to the previously placed single implant proved reliable. A logical treatment solution is to use 2 implants for the replacement of a single molar to avoid prosthodontic complications.     

A holistic model of advocacy: factors that influence its use

Although advocacy is embraced by nursing as an essential component of holistic philosophy, its scope is often limited in practice. In this article, a research study that examined the use of an expanded definition of advocacy is described. A link to the role of advocacy as a complementary therapy and in relation to facilitating the use of complementary therapies by patients is provided. Fifty-two registered nurses completed a researcher developed advocacy research instrument that assessed the use of moral-ethical, legal, political, spiritual, and substitutive advocacy along with various factors thought to influence the use of advocacy including moral development, perceived assertiveness, and perceived job security. An additional 40 RN-BSN students generated case studies of advocacy enacted in practice that were used as examples of the five categories of advocacy and to support the findings of the survey. Results indicated that moral-ethical advocacy was used more often than the other four categories. Moral stage development had a significant effect on substitutive advocacy but assertiveness and job security were not significant factors influencing any category of advocacy.     

Knock before you enter

Early on Christmas morning I am suddenly awakened by the high-pitched sound of my pager. It screeches like a smoke alarm, piercing right through to my bones. Although I have become accustomed to the sound, I still feel disoriented when roused from my sleep, and for a moment, feel entirely disoriented.     

Nutritional support in the critically injured

Nutritional support must be an integral part of the management of trauma victims. This article compares the stress response, a maladaptive response, and starvation, an adaptive process, examines the clinical research regarding total parenteral nutrition and total enteral nutrition, provides an evidence-based approach to initiating nutritional support in critically injured patients, and discusses considerations in selecting nutritional formulas.