Modulating effects of posttraining epinephrine on memory: Involvement of the amygdala noradrenergic system

These experiments examined the effects, on retention, of posttraining intra-amygdala administration of norepinephrine (NE), and propranolol. Rats were trained on a one-trial step-through inhibitory avoidance task and tested for retention 24 h later. Injections were administered bilaterally (1.0 microliter/injection) through chronically-implanted cannulae. Low doses of NE (0.1 or 0.3 microgram) administered shortly after training enhanced retention while higher doses (1.0 or 5.0 micrograms) were ineffective. Retention was not affected by NE administered 3 h after training. The effect of intra-amygdala NE on retention is blocked by simultaneous administration of propranolol (0.2 microgram). This finding suggests that the memory-enhancing effect of NE may be mediated by beta-receptors. Posttraining intra-amygdala NE also attenuated the retention deficit produced by adrenal demedullation. Further, intra-amygdala injections of propranolol (0.2 microgram) blocked the enhancing effect, on retention, of posttraining s.c. injections of epinephrine. These findings suggest that activation of noradrenergic receptors in the amygdala may be involved in memory processing and may play a role in the memory-modulating effect of peripheral epinephrine.     

A qualitative investigation of seniors' and caregivers' views on pain assessment and management.

The literature suggests that pain in the elderly, especially among seniors with dementia, is under-assessed and under-treated.This qualitative study solicited the perspectives of seniors, front-line nursing staff, nursing-home administrators, and informal caregivers of seniors with dementia on the current status of pain assessment and management. The views of these participants complement the research findings reported in the literature. While some of their explanations and potential solutions concerning under-treatment of pain in seniors echo views that have been presented in the literature, the participants also pointed to factors and avenues that have been given less formal consideration (e.g., systemic barriers to effective assessment and treatment of pain).They also highlighted the need for pain-control strategies beyond medication. The implications of these findings are discussed.     

Constitutive and 3-methylcholanthrene-induced rat ALDH3A1 expression is mediated by multiple xenobiotic response elements.

The rat class 3 aldehyde dehydrogenase gene (ALDH3A1) is expressed constitutively or by xenobiotic induction depending on the tissue in which it occurs. Although the mechanism that mediates inducible expression has been well characterized, relatively little is known about constitutive regulatory mechanisms. Previous ALDH3A1 promoter analyses have indicated that primary regulatory regions within the ALDH3A1 5' flanking region exert similar effects on both constitutive and inducible ALDH3A1 expression. However, promoter gene analyses that served as the basis of early work were limited by the lack of sufficient 5' flanking region sequence. To gain a more complete picture of how the 5' flanking region regulates both modes of expression, we have subcloned an 8.0-kilobase (kb) fragment from the 5' flanking region of the ALDH3A1 gene and subjected it to reporter gene analyses. We found a region located between 4.8 and 7.8 kb upstream of the noncoding first exon that drives strong ALDH3A1 reporter activity. This region contains xenobiotic response element consensus sequences that mediate constitutive and inducible ALDH3A1 reporter gene expression. Using the new generation of ALDH3A1 reporter constructs, we were unable to confirm the presence of a negative regulatory region that was apparent in previous studies using a shorter fragment of the 5' flanking region. We also demonstrate that 3-methylcholanthrene induces ALDH3A1 expression above high constitutive background in corneal epithelial cells.     

Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

Thermoregulation in mice following acute administration of lead acetate

Several reports in the literature suggest a relationship between lead intoxication and thermoregulatory capacity. To investigate the effects of lead on the control of body temperature, mice of the BALB/c strain were injected intraperitoneally with lead acetate (0 to 100 mg/kg) while colonic temperature was measured 30, 60, and 90 min post-injection at ambient temperatures (Ta) of 20 and 30 degrees C. Lead acetate caused a transient hypothermia, an effect which was augmented at cooler Ta's. In a second experiment, mice were injected with 100 mg/kg lead acetate and placed in a longitudinal temperature gradient to measure their preferred Ta. Lead acetate significantly reduced the preferred Ta during the first 30 min post-injection which augmented the lead-induced hypothermia. In a third experiment it was found that lead acetate-induced lethality was potentiated with increasing Ta. Hence, the hypothermic response to acute lead acetate treatment may be beneficial to survival.     

Clinical Observations of Porcelain Veneers: A Three-Year Report

One hundred and sixty-five Cerinate porcelain veneers were placed by 11 private practice clinicians from diverse locations throughout the USA. The veneers were evaluated over a 3-year service period using Kodachrome photographs and grading of clinical characteristics by evaluators. The following factors were evaluated: (1) esthetics; (2) margin fit; (3) margin discoloration; (4) breakage; (5) gingival irritation; (6) patient acceptance; and (7) caries. Specific characteristics and their evaluations over three years were: (1) Esthetics started out excellent and remained that way; (2) Margin fit was acceptable at the beginning of the study and was actually perceived to improve, perhaps related to cement at the margins wearing and smoothing; (3) Margin discoloration started very low and became slightly worse; (4) Breakage was present during each of the 3 years, and 13 percent of veneers had some breakage after 3 years. Changes in clinical procedures are suggested in this paper to diminish this problem; (5) Gingival irritation was minimal throughout the study; (6) Patient acceptance was excellent at the beginning of the study and improved; and (7) Dental caries involvement was minimal, with only one veneered tooth showing caries involvement. Over the 3-year period, the veneers provided excellent service overall.     

Targeted routine asthma care in general practice using telephone triage

BACKGROUND: There is a high non-attendance rate for traditional clinic-based routine asthma care in general practice. Alternative methods of providing routine asthma care need to be examined. AIM: To examine the cost and effectiveness of targeted routine asthma care in general practice using telephone triage, compared to usual clinic care. DESIGN OF STUDY: An open randomised controlled trial. SETTING: A single semi-rural practice in the southwest of England. METHOD: Adult patients with asthma were randomised to receive either their routine asthma care in the surgery or care by telephone triage. Asthma control parameters, health status and NHS resource utilisation were measured over the 12-month study period. RESULTS: One hundred and ninety-four patients were randomised and 35% per cent more patients (n = 84 versus n = 62) received more than one consultation in the telephone group. Asthma control as measured by the asthma control questionnaire (ACQ) was similar in the clinic and telephone groups: mean change in ACQ = -0.11 (95% CI = -0.32 to 0.11) versus -0.18 (95% CI = -0.38 to 0.02). Mean NHS costs were 210 pounds sterling per patient per year in the telephone group compared to 334 pounds sterling in the clinic group (P-value of bootstrapped difference = 0.071). CONCLUSION: Targeted routine asthma care by telephone triage of adult asthmatics can lead to more asthma patients being reviewed, at less cost per patient and without loss of asthma control compared to usual routine care in the surgery.