Imaging of atherosclerosis.

It is now well recognized that the atherosclerotic plaques responsible for thrombus formation are not necessarily those that impinge most on the lumen of the vessel. Nevertheless, clinical investigations for atherosclerosis still focus on quantifying the degree of stenosis caused by plaques. Many of the features associated with a high-risk plaque, including a thin fibrous cap, large necrotic core, macrophage infiltration, neovascularization, and intraplaque hemorrhage, can now be probed by novel imaging techniques. Each technique has its own strengths and drawbacks. In this article, we review the various imaging modalities used for the evaluation and quantification of atherosclerosis.

The use of contrast enhanced ultrasound in carotid arterial disease.

Traditionally, stroke risk stratification has centred on the degree of internal carotid artery stenosis, and the presence of focal neurological symptoms. However, degree of stenosis alone is a relatively poor predictor of future stroke in asymptomatic patients; the Asymptomatic Carotid Surgery Trial highlighting the need to identify a subgroup of asymptomatics that may benefit from intervention. Attempting to define this subgroup has inspired imaging research to identify, in vivo, high-risk plaques. In addition to pre-operative risk stratification of carotid stenosis, contrast enhanced ultrasound (CEUS) may be employed in monitoring response to plaque-stabilising therapies. Unlike most contrast agents used for computed tomography and magnetic resonance imaging, microbubbles used in CEUS remain within the vascular space and can hence be used to study the vasculature. In addition to improving current carotid structural scans, CEUS has potential to add extra information on plaque characteristics. Furthermore, by targeting microbubbles to specific ligands expressed on vascular endothelium, CEUS may have the ability to probe plaque biology. This review describes the current carotid ultrasound examination and the need to improve it, rationale for imaging neovascularisation, use of CEUS to image neovascularisation, microbubbles in improving the structural imaging of plaque, potential problems with CEUS, and future directions.

Functionally weighted airway sparing (FWAS): a functional avoidance method for preserving post-treatment ventilation in lung radiotherapy.

Recent changes to the guidelines for screening and early diagnosis of lung cancer have increased the interest in preserving post-radiotherapy lung function. Current investigational approaches are based on spatially mapping functional regions and generating regional avoidance plans that preferentially spare highly ventilated/perfused lung. A potentially critical, yet overlooked, aspect of functional avoidance is radiation injury to peripheral airways, which serve as gas conduits to and from functional lung regions. Dose redistribution based solely on regional function may cause irreparable damage to the 'supply chain'. To address this deficiency, we propose the functionally weighted airway sparing (FWAS) method. FWAS (i) maps the bronchial pathways to each functional sub-lobar lung volume; (ii) assigns a weighting factor to each airway based on the relative contribution of the sub-volume to overall lung function; and (iii) creates a treatment plan that aims to preserve these functional pathways. To evaluate it, we used four cases from a retrospective cohort of SAbR patients treated for lung cancer. Each patient's airways were auto-segmented from a diagnostic-quality breath-hold CT using a research virtual bronchoscopy software. A ventilation map was generated from the planning 4DCT to map regional lung function. For each terminal airway, as resolved by the segmentation software, the total ventilation within the sub-lobar volume supported by that airway was estimated and used as a function-based weighting factor. Upstream airways were weighted based on the cumulative volumetric ventilation supported by corresponding downstream airways. Using a previously developed model for airway radiosensitivity, dose constraints were determined for each airway corresponding to a <5% probability of airway collapse. Airway dose constraints, ventilation scores, and clinical dose constraints were input to a swarm optimization-based inverse planning engine to create a 3D conformal SAbR plan (CRT). The FWAS plans were compared to the patients' prescribed CRT clinical plans and the inverse-optimized clinical plans. Depending on the size and location of the tumour, the FWAS plan showed superior preservation of ventilation due to airflow preservation through open pathways (i.e. cumulative ventilation score from the sub-lobar volumes of open pathways). Improvements ranged between 3% and 23%, when comparing to the prescribed clinical plans, and between 3% and 35%, when comparing to the inverse-optimized clinical plans. The three plans satisfied clinical requirements for PTV coverage and OAR dose constraints. These initial results suggest that by sparing pathways to high-functioning lung subregions it is possible to reduce post-SAbR loss of respiratory function.

Sex chromosome anomalies, hormones, and sexuality.

Behavioral investigation of men with sex chromosome anomalies has been primarily limited to the study of institutionalized individuals or patient groups. A double-blind controlled investigation of XYY and XXY men found in a birth cohort of 4591 tall men born in Copenhagen gathered sexual information and assessed the role of hormonal determinants on sexual behavior. There were significant differences in several sexual dimensions and in gender role between XYY men and their controls and XXY men and their controls as well as between XYY and XXY men. Although both proband groups differed from each other and from their controls in pituitary gonadal function, there was no evidence that adult hormonal levels mediate the effect of sex chromosome anomalies on male sexuality.

Sex chromosome anomalies, hormones, and aggressivity.

This double-blind, controlled study of XYY and XXY men found in a birth cohort of 4,591 tall men born in Copenhagen assessed evidence of delinquent and aggressive behavior and explored the role of hormonal determinants in the behavioral and psychological differences noted among groups. Information from social records, a structured psychological interview, and projective tests did not support the notion that men with sex chromosome anomalies are particularly violent or aggressive. Hormonally, XYY men had significantly higher concentrations of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) than matched control groups. In contrast, XXY men had higher levels of LH, FSH, and prolactin, but low concentrations of testosterone. There was a significantly positive relation among all subjects as well as XY controls alone between plasma testosterone level and evidence of criminal convictions. A proportionate increase in testosterone levels was noted when subjects were divided into nondelinquents, delinquents without violent convictions, and delinquents with violent convictions. The relation between testosterone level and criminal behavior was not reflected in measures of aggression derived from the psychological interview and projective tests. There was no specific evidence that testosterone is a mediating factor in the criminal behavior of XYY men.

Intravenous Furosemide for Acute Decompensated Congestive Heart Failure: What Is the Evidence?

Use of intravenous furosemide rather than oral administration in acute decompensated congestive cardiac failure is universally recommended in international guidelines. We argue that this recommendation is not supported by the existing evidence, and suggest that trials should be performed to determine whether larger doses of oral furosemide should be prescribed prior to an IV switch. This could reduce length of hospital admissions and allow for more patients to be managed in the primary care setting.

Cognitive abilities in left-handers: writing posture revisited.

Among 1848 young men appearing before the Danish draft board, 232 (13%) were left-handed. Of these, 118 (51%) used an inverted, or hook-like, writing posture, 49 (21%) used a non-inverted posture and the remaining 65 (28%) could not be categorized. There were no differences between left- and right-handers on a battery of four cognitive tests. However, inverted left-handers performed significantly or near-significantly better than the non-inverted left-handers on two of the four tests and significantly better on the total score for the test battery. These results support the contention that the inverted posture is adaptive for left-handers and suggest that it may be more likely to be adopted by those with better cognitive abilities. Our findings conflict with earlier reports from two decades ago, however, and the association may therefore be socially and culturally dependent.

Spirocyclic restriction of nucleosides. An analysis of protecting group feasibility while accessing prototype anti-1-oxaspiro[4.4]nonanyl mimics.

[reaction: see text] The first spirocyclic nucleoside featuring a beta-hydroxyl (anti) at C5' has yielded to synthesis. While the OMOM functionality proved to be sensitive to the conditions necessary to incorporate heterocyclic bases, PMB protection of the carbinol was readily accommodated. The remarkably similar minimum-energy conformations of the title compounds relative to natural thymidine as deduced by Amber calculations in the gas phase are noted.

Adjusted and unadjusted energy usage rates both determine body fat and plasma leptin in male Fischer 344 rats.

Previous studies of the relationship between plasma leptin and energy usage have yielded contradictory findings. The present study was therefore conducted to clearly distinguish and measure the energy usage rate and the energy usage rate adjusted for a surrogate of metabolically active tissue mass. We investigated the simultaneous relationships between these two measures of energy usage, leptin, and body fat in 21-month-old adult male Fischer 344 rats on three different long-term dietary regimens: (1) continuous ad libitum feeding (Ad-lib); (2) ad libitum feeding until early adulthood, and then continuous 60% caloric restriction (CR); and (3) ad libitum feeding until early adulthood, then 60% caloric restriction until 16 months, and then ad libitum feeding for 5 months (CR/Ad-lib). Two versions of the daily usage rate were measured: daily dietary caloric intake (DCI), and daily energy expenditure (EE) based on indirect calorimetry. Two versions of the metabolically active tissue mass were also measured: fat-free mass (FFM), and the sum of the weight of the heart, brain, liver, and kidneys. Energy usage rates were adjusted for these measures of metabolically active tissue mass to yield measures of the energy metabolic rate. Correlation, regression, and path analyses showed that both the energy usage rate and adjusted energy usage rate played important independent roles in determining body fat and plasma leptin, but only after multivariate techniques were used to account for the simultaneous interactions between variables. Increases in the energy usage rate were associated with increases in body fat and the adjusted energy usage rate. Increases in the adjusted energy usage rate were associated with decreases in body fat and plasma leptin. These findings suggest that differences in subjects adjusted energy usage rate could explain some of the apparently contradictory findings concerning the relationship between energy usage and plasma leptin in previously published studies. In conclusion, this appears to be the first study to clearly separate and quantify the effects of the energy usage rate and adjusted energy usage rate on body fat and plasma leptin. The findings suggest that under conditions of long-term stable body weight, both of these measures of energy usage play independent simultaneous roles in determining body fat and plasma leptin.

Dot Enumeration Perceptual Organization Task (DEPOT): evidence for a short-term visual memory deficit in schizophrenia.

The Dot Enumeration Perceptual Organization Task (DEPOT) evaluates the validity of 2 specific competing cognitive models of early input dysfunction in schizophrenic individuals: a primary Stage 1, sensory store, perceptual organization deficit vs. a Stage 2, short-term visual memory (STVM) deficit. DEPOT was also designed to assess the hypothesis that schizophrenic individuals tend to perform poorly on all cognitive tasks. In DEPOT both number and form judgments are made about the same dot patterns. A response delay manipulation assesses the persistence and operation of STVM. The study included 41 psychotic inpatients (8 with acute and 16 with chronic schizophrenia and 7 with bipolar and 10 with nonbipolar affective disorder) and 38 controls (22 college students and 16 hospital personnel). Although the pattern of results was consistent with neither the Stage 1 deficit nor the general deficit hypotheses, a Stage 2, STVM deficit hypothesis could account parsimoniously for the data.

Mood alteration with yoga and swimming: aerobic exercise may not be necessary.

The mood benefits of Hatha yoga and swimming, two activities that differ greatly in aerobic training benefits, were examined. College students (N = 87) in two swimming classes, a yoga class, and a lecture-control class completed mood and personality inventories before and after class on three occasions. A multivariate analysis of variance indicated that both yoga participants (n = 22) and swimmers (n = 37) reported greater decreases in scores on Anget, Confusion, Tension, and Depression than did the control students (n = 28). The consistent mood benefits of yoga supported our earlier observation that the exercise need not be aerobic to be associated with mood enhancement. However, underlying and causal mechanisms remain uncertain. Among the men, the acute decreases in Tension, Fatigue, and Anger after yoga were significantly greater than those after swimming. Yoga may be even more beneficial than swimming for men who personally select to participate. The women reported fairly similar mood benefits after swimming and yoga. It seems that aerobic exercise may not be necessary to facilitate the mood benefits. Also, students with greater mood changes attended class more regularly than those who reported fewer psychological benefits. Maximizing the immediate psychological benefits of exercise might be one way to encourage adults to be physically active.

Relation of low and moderate intensity exercise with acute mood change in college joggers.

This study investigated a possible relationship between exercise intensity and mood alteration that commonly is associated with physical activity. 91 college students completed the Profile of Mood States before and after 20 min. of jogging at three intensities: 55%, 75%, and 79% of age-adjusted maximum heart rate on different occasions. Exercisers also completed a demographic inventory, a Lie Scale, and the State-Trait Anxiety Inventory. Contrary to our expectations, the interaction between exercise intensity and pre-post mood benefits was not significant. Supporting the manipulation of exercise intensity, the univariate interaction between exercise intensity and pre-post exercise scores on Fatigue was significant. Joggers reported short-term mood benefits on the combined subscales of the Profile of Mood States, and each subscale contributed to the benefits. Thus, regardless of the low- or moderate-intensity, participants reported that they "felt better" after exercising.

Clinical assessment of carotid atherosclerosis inflammation by positron emission tomography.

Stroke caused by carotid atherosclerosis is a leading cause of mortality and the leading cause of disability in the developed world. For carotid plaques within the neurovascular territory of a recent stroke or transient ischaemic attack, surgical removal of the plaque (endarterectomy) has been clearly shown to reduce future cerebrovascular events. Management of asymptomatic plaques, however, is less clear because only a minority of these plaques will ultimately become symptomatic. Inflammation is a key feature which predicts whether a plaque is likely to rupture and hence lead to stroke. By identifying inflammation in vivo, positron emission tomography (PET) may be able to identify high risk plaques. This will allow clinicians to target intensive medical or surgical treatment to high risk patients.