Short term arterial remodelling in the aortae of cholesterol fed New Zealand white rabbits shown in vivo by high-resolution magnetic resonance imaging — implications for human pathology

High-resolution, non-invasive imaging methods are required to monitor progression and regression of atherosclerotic plaques. We investigated the use of MRI to measure changes in plaque volume and vessel remodelling during progression and regression of atherosclerosis in New Zealand White rabbits. Atherosclerotic lesions were induced in the abdominal aorta by balloon injury and cholesterol feeding. MR images (2D) of the abdominal aorta were acquired with cardiac and respiratory gating using a fast spin echo sequence with and without fat-suppression. In an initial study on rabbits treated for 30 weeks we imaged the aortae with a spatial resolution of 250x250 micrometers with a slice thickness of 2 mm and achieved a close correlation between MRI-derived measurements and those made on perfusion pressure-fixed histological sections (r(1) = 0.83, slope p(1) < 0.01). We subsequently imaged 18 rabbits before and periodically during 12 weeks of cholesterol feeding (progression) followed by 12 weeks on normal diet (regression). Aortic wall (atherosclerotic lesion) volume increased significantly during progression and decreased during regression. In contrast, lumen volume increased during progression and did not change during regression. In conclusion, this study confirms that non-invasive, high-resolution MRI can be used to monitor progression and regression of atherosclerosis, each within 3 months and shows, for the first time in a short-term model, that positive remodelling occurs early during progression and persists through regression of atherosclerotic lesions.     

The role of PET imaging in lymphoma

Positron emission tomography using fluorine-18 (FDG-PET) is increasingly used in the staging and follow-up of malignant lymphomas, although its precise role has not yet been determined. This review considers the results reported at the different stages in the disease history and separately considers the major histological subtypes. Attention is given to the situations in which PET scanning is most likely to influence management. Finally, this review discusses ongoing developments in PET scanning with improved resolution and different radiolabelled tracers.     

National databases and clinical practice specialist: decreasing postoperative atrial fibrillation following cardiac surgery

In this article, we document how an interdisciplinary committee of health professionals led to an approximate 50% reduction in the incidence of postoperative atrial fibrillation (AF) following a cardiac surgery procedure by using preoperative loading and dosing of PO amiodarone and beta blockade. Patients in this report (n = 3397) included all coronary artery bypass surgery (CABG) and valve replacement/repair procedures from January 1, 2000 to June 30, 2002. The incidence of postoperative AF for a CABG or valve replacement/repair procedure was 19.0% for period A (preprotocol) and 13.5% for period B (postprotocol). This translates into an absolute risk reduction of 5.5% or 113 actual cases of postoperative AF reduced. The role of the clinical practice specialist, a master's prepared nurse, and participation in the national Society of Thoracic Surgeon's database allowed us to track our CABG outcomes, benchmark our outcomes against both national and regional institutions, and make changes in outcomes incidence through performance improvement.     

An fMRI investigation of speech and tone segmentation

Recent research strongly indicates that phonological tasks activate a subregion of the inferior frontal gyrus. The purpose of the present fMRI study was to investigate the extent to which activation of this region during phonological processing is due to speech processes per se such as articulatory recoding or to other cognitive task demands such as working memory. Thus, we compared activation patterns during segmentation of speech and tone sequences to a tone discrimination task. In particular, participants performed same/different judgments on pairs of words, pseudowords, and tone sequences that required segmentation of a continuous acoustic signal as well as tone pairs that did not require segmentation. Accuracy and reaction time data showed that speech and tone sequence segmentation conditions patterned more similarly to each other than to tone discrimination pairs. Analyses of group data revealed strong activation of the region at the border of the left inferior and middle frontal gyrus for all three segmentation conditions compared to tone discrimination, but no consistent differences were observed when word and pseudoword segmentation were directly contrasted. Analyses of individual subjects indicated that a large number of participants activated a small area of the middle frontal gyrus during the speech conditions compared to the sequences. These results suggest that a significant portion of active frontal areas is recruited for extracting acoustic information and maintaining it in memory for decision. However, some regions at the border of the inferior/middle frontal gyrus may be unique to speech segmentation.     

The effect of donepezil on sedation and other symptoms in patients receiving opioids for cancer pain: a pilot study

Opioid-induced sedation is a major complication in patients with cancer pain. This study assessed the effectiveness of donepezil in opioid-induced sedation and related symptoms in patients with cancer pain. Twenty-seven patients who were receiving strong opioids for pain and reported sedation were enrolled. Donepezil 5 mg was given every morning for 7 days. Changes between baseline and Day 7 in sedation, pain, fatigue and other symptoms were evaluated using the Edmonton Symptom Assessment Scale. Fatigue was also measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Overall usefulness of donepezil was measured by the patient at the end of the study. In 20 evaluable patients, sedation, fatigue, anxiety, well-being, depression, anorexia and problems with sleep were significantly improved. Side effects included nausea, vomiting, diarrhea, muscle and abdominal cramps, and anorexia. Overall, however, the treatment was well tolerated. Donepezil appears to improve sedation and fatigue in patients receiving opioids for cancer pain. Randomized controlled trials of this agent are justified.     

Antiherpes virus activities of new 6-19 carbon-bridged steroids and some synthetic precursors

Three synthetic 6,19-carbon bridged steroids: 3beta,20beta-diacetyloxy-5alpha-chloro-19a(R)-hydroxy-6,19-methanopregnane, 3beta,20beta-diacetyloxy-5alpha-chloro-6,19-methanopregnane, 6,19-methanopregn-4-ene-3,20-dione and four synthetic precursors: 3beta,20beta-diacetyloxy-19-hydroxypregn-5-ene, 3beta,20beta-diacetyloxy-pregn-5-en-19-al, 3beta,20beta-diacetyloxy-19(E)-(methoxymethylidene)-pregn-5-ene and 20beta-acetyloxy-3beta-hydroxy-19(E)-(methoxymethylidene)-pregn-5-ene were tested against herpes virus replication in cell cultures. Several compounds were cytotoxic for stationary cells. Antiviral studies performed with all compounds against HSV-1 indicated a dose-dependent virus susceptibility with selectivity indexes (SI) values in the range 1.7-183.2. Selected compounds were also tested against HSV-2 and the SI values obtained were in the range of 31-273. Attempts to reveal the step of virus multiplication affected by pregnanes were performed with one compound. HSV-1 virus incubation with the compound did not alter the ability of virus particles to infect cells; moreover, neither virus adsorption nor penetration appeared to be affected. The drug must be present during at least the first 7 h of the virus cycle to inhibit more than 90% of virus production. All these results suggest that these novel molecules interfere with an intracellular step of virus multiplication, thus behaving like true antivirals.     

Introduction of a community nutrition risk assessment tool

This article describes the introduction of a community nutrition risk assessment (CNRA) initiative in liaison with a local primary care trust (PCT). A pilot was undertaken in order to produce local evidence of the benefits of nutrition risk screening and thus gain support from the PCT for full implementation of the CNRA. The results from the pilot, which indicated that a substantial financial saving for the PCT was possible with a corresponding improvement in patient care, were sufficiently convincing for the PCT to sanction the introduction of the CNRA throughout the local community. Seven steps for success are recommended which may be of use to other healthcare professionals who are considering such a process for their own community patients or indeed any other multiprofessional initiative which requires PCT support. Such steps include identification of those who may help or hinder the process and a thorough preparation of a concise evidence-based proposal which should assist in persuading those less enthusiastic to accept and support the vision.