Role of glucocorticoids in the regulation of pituitary somatostatin receptor subtype (sst1-sst5) mRNA levels: evidence for direct and somatostatin-mediated effects

Glucocorticoids can differentially regulate somatostatin (SRIH) receptor subtype expression depending on the duration of treatment, dose used and tissue type examined. In order to determine if glucocorticoids are critical regulators of pituitary SRIH receptor synthesis in vivo, we examined the effect of adrenalectomy (ADX), with and without dexamethasone (DEX; 200 microg/day for 8 days) treatment, on the relative expression levels of the SRIH receptor subtypes, sst1-sst5, by multiplex RT-PCR. ADX increased pituitary sst2 mRNA levels, but did not significantly alter mRNA levels of the other SRIH receptor subtypes. These findings indicate that pituitary sst2 synthesis is normally under inhibitory control of endogenous glucocorticoids. High-dose DEX resulted in a decrease in sst1-sst4 mRNA and an increase in sst5 mRNA, independent of adrenal status. DEX also decreased sst2, sst3 and sst4 mRNA levels and increased sst5 mRNA levels by short-term in vitro application (10 nM, 4 h) in primary rat pituitary cell cultures, indicating DEX regulation of sst2-sst5 in vivo is at least in part due to a direct action at the level of the pituitary. However, the inhibitory actions of DEX on sst1 mRNA levels observed in vivo were not consistently replicated in vitro. In order to determine if the somatotrope population of the pituitary would display a similar response to DEX, fluorescent-activated cell sorting was used to obtain somatotrope-enriched cultures (>95% growth hormone immunopositive cells). DEX treatment (10 nM, 4 h) of somatotropes decreased sst2 and sst3, but did not alter sst5 mRNA levels. These results indicate that the effects of DEX on sst5 mRNA levels observed in unsorted pituitary cell cultures might be due to changes in sst5 expression in pituitary cell types other than somatotropes. Since excess glucocorticoids are thought to enhance SRIH tone, we also tested if ligand activation of SRIH receptor subtypes in vitro could mimic any of the actions of DEX on SRIH receptor mRNA levels observed in vivo. To this end, unsorted pituitary cell cultures and somatotrope-enriched cultures were treated with SRIH (1 and 100 nM) for 4 h. SRIH increased sst3 and sst5 mRNA levels, in both culture systems. These results suggest that the DEX-induced increase in endogenous SRIH tone may contribute to enhanced sst5 mRNA levels observed in vivo. However, the stimulatory actions of SRIH on sst3 mRNA levels observed in vitro might be overridden by direct inhibitory actions of DEX.     

Profiles of respite use

Profiles of long-term respite use are reported for a diverse sample of 4,369 families from seven states who participated in the Alzheimer's Disease Demonstration Grant to States program. Data from service records spanning a period of seven years were analyzed using hierarchical linear modeling techniques. Respite use was examined in both day care and in-home settings using three different measures of use. Client characteristics related to use include the caregiver's gender and relationship to the elder, and the ethnicity, income, functional level, and problem behaviors of the elder. Provider characteristics linked with different patterns of use include level of service, fee structure, and level of capitation. Implications for service delivery are discussed.     

Differences in DNA binding properties between E2F1 and E2F4 specify repression of the Mcl-1 promoter

E2F1 is a potent inducer of apoptosis whereas its relative, E2F4, generally does not promote cell death. Other work from our laboratory has demonstrated that E2F1 can directly bind and represss the Mcl-1 promoter - contributing to E2F1-mediated apoptosis. Here we show that while E2F1 can repress the Mcl-1 promoter, other members of the E2F family (such as E2F4) cannot. Characterization of the Mcl-1 promoter demonstrates that the -143/+10 region is critical for E2F1-mediated downregulation. We demonstrate that the ability of E2F1 to repress the Mcl-1 promoter correlates with its ability to bind within the required -143/+10 region of this promoter. In contrast, E2F4 is unable to bind to the -143/+10 region of the Mcl-1 promoter. We propose that E2F4 is unable to repress the Mcl-1 promoter primarily as a result of insufficient binding to the essential regulatory region. This is the first evidence of DNA binding specificity among E2F family members that results in differential regulation of a naturally occurring promoter.     

Spatial event cluster detection using an approximate normal distribution

Background  

In geographic surveillance of disease, areas with large numbers of disease cases are to be identified so that investigations of the causes of high disease rates can be pursued. Areas with high rates are called disease clusters and statistical cluster detection tests are used to identify geographic areas with higher disease rates than expected by chance alone. Typically cluster detection tests are applied to incident or prevalent cases of disease, but surveillance of disease-related events, where an individual may have multiple events, may also be of interest. Previously, a compound Poisson approach that detects clusters of events by testing individual areas that may be combined with their neighbours has been proposed. However, the relevant probabilities from the compound Poisson distribution are obtained from a recursion relation that can be cumbersome if the number of events are large or analyses by strata are performed. We propose a simpler approach that uses an approximate normal distribution. This method is very easy to implement and is applicable to situations where the population sizes are large and the population distribution by important strata may differ by area. We demonstrate the approach on pediatric self-inflicted injury presentations to emergency departments and compare the results for probabilities based on the recursion and the normal approach. We also implement a Monte Carlo simulation to study the performance of the proposed approach.     

Assessing the Health Attitudes, Beliefs, and Behaviors of African Americans Attending Church: A Comparison from Two Communities

Public health officials and researchers continue to be increasingly concerned about the health of populations of color, especially African Americans. A survey was administered in African American churches in two communities (Wichita, KS and Tuscaloosa, AL) to gather information concerning health behaviors and beliefs and to design interventions that might improve their health status. The study examined the homogeneity of attitudes, beliefs, and behaviors across these samples and to determine the readiness to change using the Transtheoritical Model. Individuals completed a 33-item survey: 6 demographic questions, 12 health behavior questions, 8 health belief questions, 3 church attendance questions, and 4 church-based health promotion program questions. The total sample consisted of 429 respondents. The results showed that 93% of respondents have had their blood pressure checked in the past 2 years. While only 44% indicated eating a high fiber diet during the week. Thirty percent of respondents indicated that their health was dependent on fate or destiny. The findings from this study confirm that among both samples that health attitudes, beliefs, and behaviors need to be changed to lower the risk of certain diseases and disorders. The findings also indicate that both samples have similar beliefs about health that may have important implications for disseminating information to the community. Innovative and culturally sensitive programs are needed in the African American community if disparities in health are to diminish.     

Poor sleepers who do not complain of insomnia: Myths and realities about psychological and lifestyle characteristics of older good and poor sleepers

Psychological adjustment, lifestyle, and sleep parameters were investigated in 634 older community residents. Participants were divided into three categories: good sleepers, poor sleepers experiencing high distress, and poor sleepers experiencing minimal distress. Results indicate that (1) highly distressed poor sleepers manifested an anxious, depressed, negative cognitive-affective set; (2) many coped well with age related changes in sleep quality—they resembled good sleepers in the relative absence of psychological maladjustment they displayed; (3) the three groups had similar lifestyles, but they differed in the cognitive-affective evaluation of their activities, (4) the insomnia complaint is itself multifaceted and is comprised of three distinct elements—difficulty sleeping, distress, and daytime fatigue; (5) sleep practices (e.g., naps, bedtimes) are not implicated in chronic poor sleep; and (6) many commonly held assumptions about sleep disruptions in older individuals are myth rather than reality. Implications for better understanding and treating insomnia in older individuals are discussed.This article was prepared during the tenure of grants from the Conseil Québécois de la recherche sociale, Health and Welfare Canada, and the Direction générale de l'enseignement collégial. We are grateful for the generous support of these organizations. In addition, we would like to thank the dedicated members of our research team: Sally Bailes, Ann Gay, Jason Lavers, John Martos, Kathleen McAdams, Vicki Tagalakis, and most especially, Harriet Lennox for their substantial contribution to this research.Dawson College.Sir Mortimer B. Davis—Jewish General Hospital.Concordia University.McGill University.     

Objective assessment of videoconferenced lectures in a surgical clerkship

BACKGROUND: A challenge to the practice of third-year clerkship rotations at remote locations is the maintenance of equivalent didactic lectures, especially in subspecialty components. There has been little objective assessment of the results of videoconference lectures on medical student clerkship education. METHODS: Third-year surgical clerkship students, randomly assigned to a 4-week rotation 75 miles from the medical school, received subspecialty lectures by interactive teleconference via an ISDN line at 128 kb/s. Weekly quiz results (% correct) of students who received videoconference lectures were compared with students receiving conventional lectures, and were analyzed by 2-tailed t tests for equality of means. RESULTS: A mean of 12 students were tested per quiz (range, 5-21 students) after videoconference lectures, and 98 students were tested after conventional lectures (range, 41-146 students). The mean quiz score of students receiving video lectures was 70.5% (range, 65.4% to 73.6%); and after conventional lectures the mean quiz score was 71.4% (range, 69.5% to 76.8%). There were no significant differences in the mean scores of the individual quizzes (P = .16-.92) or between the totals (P = .65). CONCLUSIONS: Telemedicine, using interactive videoconferencing, is an effective method for didactic lectures in a surgical clerkship. This technology allows students to receive interactive lectures at distant clinical sites and limit their travel.