Issues related to combining risk factor reduction and clinical treatment for eating disorders in defined populations

Population-based psychotherapy considers the provision of services to a population at risk for or already affected with a disease or disorder. Using existing data on prevalence, incidence, risk factors, and interventions (both preventive and clinical) for eating disorders (anorexia excluded), this article examines issues related to integrating and providing risk reduction and treatment to a population of female college students. Population-based psychotherapy models have important implications for the provision of services and for future directions in research on eating and other types of mental health disorders, but the assumptions need to be carefully examined. Studies that provide data combining population-based risk factor reduction and clinical treatment are needed to advance this field.     

Videoconferencing for continuing medical education: from pilot project to sustained programme

Videoconferencing has been used to provide distance education for medical students, physicians and other health-care professionals, such as nurses, physiotherapists and pharmacists. The Dalhousie University Office of Continuing Medical Education (CME) has used videoconferencing for CME since a pilot project with four sites in 1995-6. Since that pilot project, videoconferencing activity has steadily increased; in the year 1999-2000, a total of 64 videoconferences were provided for 1059 learners in 37 sites. Videoconferencing has been well accepted by faculty staff and by learners, as it enables them to provide and receive CME without travelling long distances. The key components of the development of the videoconferencing programme include planning, scheduling, faculty support, technical support and evaluation. Evaluation enables the effect of videoconferencing on other CME activities, and costs, to be measured.     

A computational ensemble pharmacophore model for identifying substrates of P-glycoprotein

P-glycoprotein (P-gp) functions as a drug efflux pump, mediating multidrug resistance and limiting the efficacy of many drugs. Clearly, identification of potential P-gp substrate liability early in the drug discovery process would be advantageous. We describe a multiple-pharmacophore model that can discriminate between substrates and nonsubstrates of P-gp with an accuracy of 63%. The application of this filter allows large virtual libraries to be screened efficiently for compounds less likely to be transported by P-gp.     

Assessment,measures and approaches to easing caregiver burden in Alzheimer's disease

The reduction of caregiver burden for those caring for patients with Alzheimer's disease (AD) is especially important given the prevalence of AD as populations age. This paper reviews the complex nature of caregiver burden, how it is measured, and possible interventions that may affect caregiver burden. Caregiver characteristics as well as symptoms exhibited by patients contribute to burden. A number of specific quantitative measures which have been developed to better evaluate caregiver burden are discussed. Such measures are also useful in measuring the impact of interventions on caregiver burden. Pharmacological treatment of patients with AD through the use of acetylcholinesterase inhibitors has positively affected cognition, activities of daily living, and behavioural problems. These benefits significantly reduce caregiver burden. The same is true for psychosocial interventions for the caregiver. It has been suggested that combining both approaches should be utilised for optimal management. Our knowledge of caregiver burden has greatly increased over the past two decades with clear benefits for both patients and caregivers. However, many aspects still clearly require further research. Given the significance of caregiver burden, various aspects have been extensively studied including contributing and protective factors, quantitative assessment, and pharmacological and psychosocial intervention. It is important for clinicians to be aware of this knowledge so that they can effectively incorporate it into their treatment plans for those affected by AD.     

Rationale for Ras and raf-kinase as a target for cancer therapeutics

Improvements in our understanding of the intrinsic aberrancies in cancer cells have enabled the design and development of novel therapeutics that specifically target these changes. Among the many complex cellular pathways and mechanisms which have been unveiled by new molecular techniques, RAS-mediated signal transduction is one met with tremendous research interests. Activation of RAS initiates several signaling cascades, of which the RAS-RAF-MEK-ERK pathway is among the better delineated, and is the main focus of this review. Other cellular consequences of RAS activation including interactions with the RHO-family proteins, the PI3-kinase pathway, and other mitogen activated protein kinase cascades, will be discussed. The intricate balance and coordination of multiple RAS-mediated signals lead to ultimate effects on cell growth, differentiation, cycling and survival. Pharmacological strategies such as analog development, synthesis of small molecule inhibitors, antisense technology, and vaccine therapy have been utilized to intervene with key RAS-signaling proteins, in an attempt to provide rational therapeutic solutions in malignant diseases.     

Inhibitors of protein farnesyltransferase as novel anticancer agents

This paper describes recent progress in the design, synthesis and biological evaluation of inhibitors for the enzyme protein farnesyltransferase (PFTase). This enzyme plays a critical role in the post-translational modification of a range of different intracellular proteins. In particular, PFTase attaches a farnesyl group to the GTPase Ras whose oncogenically mutated form is found in over 30% of human cancers. As a result PFTase inhibitors have been developed as potential cancer therapeutic drugs either by rational design based on the structure of the CAAX carboxyl terminus of Ras or random screening of chemical libraries or natural products. Some of these inhibitors show remarkable inhibition potency against PFTase at subnanomolar concentrations and >1000-fold selectivity compared to the related enzyme geranylgeranyltransferase-I. Certain of these compounds are highly effective at blocking the growth of human tumors in animal models and are now undergoing clinical trials. However, several issues in the research remain unsolved, including the mechanism by which PFTase inhibitors suppress tumor growth. Although it has been established that PFTase inhibitors block prenylation of Ras in vitro, the results in wholecells and animal studies suggest the possibility that proteins other than Ras are affected.     

Patient safety and medical malpractice: a case study

The system of tort liability for medical malpractice is frequently criticized for poorly performing its theoretical functions of compensating injured patients, deterring negligence, and dispensing corrective justice. Working from an actual malpractice case involving serious injury but no apparent negligence, the authors explore these criticisms from the perspectives of both the plaintiff-patient and the defendant-physician. They then examine the tort system through the lens of patient safety and conclude that the tensions between the system and patient safety initiatives suggest a need to reexamine our attachment to adversarial dispute resolution in health care. They propose targeted reforms that could improve the functioning of the system and create incentives to improve safety and quality.     

Chemokine stimulation of human peripheral blood T lymphocytes induces rapid dephosphorylation of ERM proteins,which facilitates loss of microvilli and polarization

Lymphocyte microvilli mediate initial rolling-adhesion along endothelium but are lost during transmigration from circulation to tissue. However, the mechanism for resorption of lymphocyte microvilli remains unexplored. We show that chemokine stimulation of human peripheral blood T (PBT) cells is sufficient to induce rapid resorption of microvilli. Microvilli in other cells are regulated by ezrin/radixin/moesin (ERM) proteins, which link the plasma membrane to the cortical F-actin cytoskeleton; maintenance of these linkages requires ERM activation, reflected by phosphorylation at a specific carboxy-terminal threonine residue. Carboxyphosphorylated-ERM (cpERM) proteins in resting PBT cells show a punctate peripheral distribution consistent with localization to microvilli. cpERM dephosphorylation begins within seconds of stimulation by chemokines (stromal derived factor 1 alpha [SDF-1 alpha] or secondary lymphoid tissue cytokine), and ERM proteins lose their punctate distribution with kinetics paralleling the loss of microvilli. The cpERM proteins are preferentially associated with the cytoskeleton at rest and this association is lost with chemokine-induced dephosphorylation. Transfection studies show that a dominant-negative ERM construct destroys microvilli, whereas a construct mimicking cpERM facilitates formation of microvilli, retards chemokine-induced loss of microvilli, and markedly impairs chemokine-induced polarization. Thus, chemokine induces rapid dephosphorylation and inactivation of cpERM, which may in turn facilitate 2 aspects of cytoskeletal reorganization involved in lymphocyte recruitment: loss of microvilli and polarization.     

Treating acute stress disorder following mild traumatic brain injury

OBJECTIVE: Acute stress disorder permits early identification of trauma survivors who are at risk of developing chronic posttraumatic stress disorder (PTSD). This study aimed to prevent PTSD in people who developed acute stress disorder after a mild brain injury by early provision of cognitive behavior therapy. METHOD: Twenty-four civilian trauma survivors with acute stress disorder were given five individually administered sessions of either cognitive behavior therapy or supportive counseling within 2 weeks of their trauma. RESULTS: Fewer patients receiving cognitive behavior therapy than supportive counseling met criteria for PTSD at a posttreatment evaluation (8% versus 58%, respectively). There were also fewer cases of PTSD at a 6-month follow-up evaluation among those receiving cognitive behavior therapy (17%) than among those receiving supportive counseling (58%). Patients in the cognitive behavior therapy condition displayed less reexperiencing and avoidance symptoms at the follow-up evaluation than patients receiving supportive counseling. CONCLUSIONS: These findings suggest that PTSD following mild brain injury can be effectively prevented with early provision of cognitive behavior therapy.