Noninvasive tests of vascular function and structure: Why and how to perform them

Background Early atherosclerosis involves the endothelium of many arteries. Information about peripheral arterial anatomy and function derived from vascular imaging studies such as brachial artery reactivity (BAR) and carotid intima media thickness (IMT) may be pertinent to the coronary circulation. The prevention and early treatment of atherosclerosis is gaining more attention, and these tests might be used as indications or perhaps guides to the effectiveness of therapy, but their application in clinical practice has been limited. This review seeks to define the anatomy and pathophysiology underlying these investigations, their methodology, the significance of their Findings, and the issues that must be resolved before their application. Methods The literature on BAR and IMT is extensively reviewed, especially in relation to clinical use. Results Abnormal flow-mediated dilation is present in atherosclerotic vessels, is associated with cardiovascular risk factors, and may be a marker of preclinical disease. Treatment of known atherosclerotic risk Factors has been shown to improve flow-mediated dilation, and some data suggest that vascular responsiveness is related to outcome. Carotid IMT is associated with cardiovascular risk factors, and increased levels can predict myocardial infarction and stroke. Aggressive risk factor management can decrease IMT. Conclusions BAR and IMT ate functional and structural markers of the atherosclerotic process. The clinical use of BAR has been limited by varying reproducibility and the influence by exogenous factors, but IMT exhibits less variability. A desirable next step in the development of BAR and IMT as useful clinical tools would be to show an association of improvement in response to treatment with improvement in prognosis.

Deletion of 8p: a report of a child with normal intelligence

The case is presented of a female infant with a distal deletion of 8p (8p23.1 --> pter) whose development was monitored over a 5-year period from 12 months of age. Although previous literature has suggested that 8p deletion is associated with mild to moderate intellectual disability, the child reported here has normal intelligence. Despite initial delays in gross motor and language skills, cognitive development (assessed with the Bayley Scales of Infant Development) and intellectual ability (measured on the Stanford-Binet Intelligence Scale) were within average range. It is argued that the small number of previous case reports may have created a misleading impression of intellectual development in individuals with distal deletions of 8p.

Adrenocorticotropin stimulation tests in patients with hypothalamic-pituitary disease: low dose, standard high dose and 8-h infusion tests

Objectives Low doses of ACTH [1-24] (0.1, 0.5 and 1.0 mug per 1.73 m(2)) may provide a more physiological level of adrenal stimulation than the standard 250 mug test, but not all studies have concluded that the 1.0 fig is a more sensitive screening test for central hypoadrenalism. Eight-hour infusions of high dose ACTH [1-24] have also been suggested as a means of assessing the adrenals' capacity for sustained cortisol secretion. In this study, we compared the diagnostic accuracy of three low dose ACTH tests (LDTs) and the 8-h infusion with the standard 250 jig test (HDT) and the insulin hypoglycaemia test (IHT) in patients with hypothalamic-pituitary disease. Subjects and design Three groups of subjects were studied. A healthy control group (group 1, n=9) and 33 patients with known hypothalamic or pituitary disease who were divided into group 2 (n=12, underwent IHT) and group 3 (n=21, IHT contraindicated). Six different tests were performed: a standard IHT (0.15 U/kg soluble insulin); a 60-minute 250 mug HDT; three different LDTs using 0.1 mug, 0.5 mug and 1.0 mug (all per 1.73 m(2)); and an 8-h infusion test (250 mug ACTH [1-24] at a constant rate over 8 h). Results Nine out of the 12 patients in group 2 failed the IHT. Three out of 12 patients from group 2 who clearly passed the IHT, also passed all the ACTH [1-24] stimulation tests. Seven of the 9 patients who failed the lHT, failed by a clear margin (peak cortisol

Determination of reference values for glucose tolerance, insulin tolerance, and insulin sensitivity tests in clinically normal cats

Objective-To determine reference values and test variability for glucose tolerance tests (GTT), insulin tolerance tests (ITT), and insulin sensitivity tests (IST) in cats, Animals-32 clinically normal cats. Procedure-GTT, ITT, and IST were performed on consecutive days. Tolerance intervals tie, reference values) were calculated as means +/- 2.397 SD for plasma glucose and insulin concentrations, half-life of glucose (T-1/2glucose), rate constants for glucose disappearance (K-glucose and K-itt), and insulin sensitivity index (S-l). Tests were repeated after 6 weeks in 8 cats to determine test variability. Results-Reference values for T-1/2glucose, K-glucose, and fasting plasma glucose and insulin concentrations during GTT were 45 to 74 minutes, 0.93 to 1.54 %/min, 37 to 104 mg/dl, and 2.8 to 20.6 muU/ml, respectively. Mean values did not differ between the 2 tests. Coefficients of variation for T-1/2glucose, K-glucose, and fasting plasma glucose and insulin concentrations were 20, 20, 11, and 23%, respectively. Reference values for K-itt were 1.14 to 7.3%/min, and for S-l were 0.57 to 10.99 x 10(-4) min/muU/ml. Mean values did not differ between the 2 tests performed 6 weeks apart, Coefficients of variation for K-itt and S-l were 60 and 47%, respectively. Conclusions and Clinical Relevance-GTT, ITT, and IST can be performed in cats, using standard protocols. Knowledge of reference values and test variability will enable researchers to better interpret test results for assessment of glucose tolerance, pancreatic beta -cell function, and insulin sensitivity in cats.

Resolution of natural groups using iterative assignment tests: an example from two species of Australian native rats (Rattus)

Sympatric individuals of Rattus fuscipes and Rattus leucopus, two Australian native rats from the tropical wet forests of north Queensland, are difficult to distinguish morphologically and are often confused in the field. When we started a study on fine-scale movements of these species, using microsatellite markers, we found that the species as identified in the field did not form coherent genetic groups. In this study, we examined the potential of an iterative process of genetic assignment to separate specimens from distinct (e.g. species, populations) natural groups. Five loci with extensive overlap in allele distributions between species were used for the iterative process. Samples were randomly distributed into two starting groups of equal size and then subjected to the test. At each iteration, misassigned samples switched groups, and the output groups from a given round of assignment formed the input groups for the next round. All samples were assigned correctly on the 10th iteration, in which two genetic groups were clearly separated. Mitochondrial DNA sequences were obtained from samples from each genetic group identified by assignment, together with those of museum voucher specimens, to assess which species corresponded to which genetic group. The iterative procedure was also used to resolve groups within species, adequately separating the genetically identified R. leucopus from our two sampling sites. These results show that the iterative assignment process can correctly differentiate samples into their appropriate natural groups when diagnostic genetic markers are not available, which allowed us to resolve accurately the two R. leucopus and R. fuscipes species. Our approach provides an analytical tool that may be applicable to a broad variety of situations where genetic groups need to be resolved.

Model specification tests in nonparametric stochastic regression models

In this paper, we consider testing for additivity in a class of nonparametric stochastic regression models. Two test statistics are constructed and their asymptotic distributions are established. We also conduct a small sample study for one of the test statistics through a simulated example. (C) 2002 Elsevier Science (USA).

Levene tests of homogeneity of variance for general block and treatment designs

This article develops a weighted least squares version of Levene's test of homogeneity of variance for a general design, available both for univariate and multivariate situations. When the design is balanced, the univariate and two common multivariate test statistics turn out to be proportional to the corresponding ordinary least squares test statistics obtained from an analysis of variance of the absolute values of the standardized mean-based residuals from the original analysis of the data. The constant of proportionality is simply a design-dependent multiplier (which does not necessarily tend to unity). Explicit results are presented for randomized block and Latin square designs and are illustrated for factorial treatment designs and split-plot experiments. The distribution of the univariate test statistic is close to a standard F-distribution, although it can be slightly underdispersed. For a complex design, the test assesses homogeneity of variance across blocks, treatments, or treatment factors and offers an objective interpretation of residual plot.

Sensitivity and specificity of pooled faecal culture and serology as flock-screening tests for detection of ovine paratuberculosis in Australia

The flock-level sensitivity of pooled faecal culture and serological testing using AGID for the detection of ovine Johne's disease-infected flocks were estimated using non-gold-standard methods. The two tests were compared in an extensive field trial in 296 flocks in New South Wales during 1998. In each flock, a sample of sheep was selected and tested for ovine Johne's disease using both the AGID and pooled faecal culture. The flock-specificity of pooled faecal culture also was estimated from results of surveillance and market-assurance testing in New South Wales. The overall flock-sensitivity of pooled faecal culture was 92% (95% CI: 82.4 and 97.4%) compared to 61% (50.5 and 70.9%) for serology (assuming that both tests were 100% specific). In low-prevalence flocks (estimated prevalence

Characterisation of chronic lateral epicondylalgia using the McGill pain questionnaire, visual analog scales, and quantitative sensory tests

Aims: To characterise chronic lateral epicondylalgia using the McGill Pain Questionnaire, Visual Analog Scales for pain and function, and Quantitative Sensory Tests; and to examine the relationship between these tests in a population with chronic lateral epicondylalgia. Method: Fifty-six patients (29 female, 27 male) diagnosed with unilateral lateral epicondylalgia of 18.7 months (mean) duration (range 1-300), with a mean age of 50.7 years (range 27-73) participated in this study. Each participant underwent assessment with the McGill Pain Questionnaire (MPQ), Visual Analog Scales (VAS) for pain and function. and Quantitative Sensory Tests (QST) including thermal and pressure pain thresholds, pain free grip strength, and neuromeningeal tissue testing via the upper limb tension test 2b (ULTT 2b). Results: Moderate correlation (r = .338-.514, p = .000-.013) was found between all indices of the MPQ and VAS for pain experienced in the previous 24 hours and week. Thermal pain threshold was found to be significantly higher in males. A significant poor to moderate correlation was found between the Pain Rating Index (PRI) in the sensory category of the MPQ and ULTT2b scores (r = .353, p = .038). There was no other significant correlation between MPQ and QST data. Pain free grip strength was poorly yet significantly correlated with duration of pathology (r = 318, p = .038). Conclusion: The findings of this study are in agreement with others (Melzack and Katz, 1994) regarding the multidimensional nature of pain, in a condition conventionally conceived as a musculoskeletal pain state. The findings also suggest that utilisation of only one pain measurement tool is unlikely to provide a thorough clinical picture of pain experienced with chronic lateral epicondylalgia.

A study of five cervicocephalic relocation tests in three different subject groups

Objective: To compare head relocation accuracy in traumatic ( whiplash), insidious onset neck pain patients and asymptomatic subjects when targeting a natural head posture (NHP) and complex predetermined positions. Design: A case-control study. Setting: University-based musculoskeletal research clinic. Participants: Sixty-three volunteers divided into three groups of similar gender and age: Group 1 (n=21) an asymptomatic group; group 2 (n=20) insidious onset neck pain; group 3 (n=22) a history of whiplash injury. Intervention: Five randomly ordered tests designed to detect relocation accuracy of the head. Outcome measures: A 3-Space Fastrak system measured the mean absolute relocation error of three trials of each relocation test. Results: A significant difference was found between groups in one of the tests targeting the NHP (p=0.001). Post-hoc pairwise comparisons revealed a significant difference (pless than or equal to0.05) between the asymptomatic group and each symptomatic group. The difference between the symptomatic groups just failed to reach significance (p=0.07). None of the other four tests revealed significant differences. Conclusion: The test of targeting the NHP indicates that relocation inaccuracy exists in patients with neck pain with a trend to suggest that the deficit may be greater in whiplash patients. Tests employing unfamiliar postures or more complex movement were not successful in differentiating subject groups.