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.

Genetics of brain function and cognition

There is overwhelming evidence for the existence of substantial genetic influences on individual differences in general and specific cognitive abilities, especially in adults. The actual localization and identification of genes underlying variation in cognitive abilities and intelligence has only just started, however. Successes are currently limited to neurological mutations with rather severe cognitive effects. The current approaches to trace genes responsible for variation in the normal ranges of cognitive ability consist of large scale linkage and association studies. These are hampered by the usual problems of low statistical power to detect quantitative trait loci (QTLs) of small effect. One strategy to boost the power of genomic searches is to employ endophenotypes of cognition derived from the booming field of cognitive neuroscience This special issue of Behavior Genetics reports on one of the first genome-wide association studies for general IQ. A second paper summarizes candidate genes for cognition, based on animal studies. A series of papers then introduces two additional levels of analysis in the ldquoblack boxrdquo between genes and cognitive ability: (1) behavioral measures of information-processing speed (inspection time, reaction time, rapid naming) and working memory capacity (performance on on single or dual tasks of verbal and spatio-visual working memory), and (2) electrophyiosological derived measures of brain function (e.g., event-related potentials). The obvious way to assess the reliability and validity of these endophenotypes and their usefulness in the search for cognitive ability genes is through the examination of their genetic architecture in twin family studies. Papers in this special issue show that much of the association between intelligence and speed-of-information processing/brain function is due to a common gene or set of genes, and thereby demonstrate the usefulness of considering these measures in gene-hunting studies for IQ.

Dynamic assessment of tongue function in children with dysarthria associated with acquired brain injury using electromagnetic articulography

The study to be presented is the first to use a new physiological device, the electromagnetic articulograph, to assess articulatory dysfunction in children with acquired brain injury. Two children with dysarthria subsequent to acquired brain injury participated in the study. One child, a female aged 12 years 9 months exhibited a mild-moderate ataxic dysarthria following traumatic head injury while the other, a male aged 13 years 10 months, demonstrated a moderate-severe flaccid-ataxic dysarthria also following traumatic head injury. The speed and accuracy of their tongue movements was assessed using the Carstens AG100 electromagnetic articulograph. Movement trajectories together with a range of quantitative kinematic parameters were estimated during performance of ten repetitions of the lingual consonants /t, s, k/ and consonant cluster /kl/ in the word initial position of single syllable words. A group of ten non-neurologically impaired children served as controls. Examination of the kinematic parameters, including movement trajectories, velocity, acceleration, deceleration, distance travelled and duration of movement, revealed differences in the speed and accuracy of the tongue movements in both children with acquired brain injury compared to those produced by the non-neurologically impaired controls. The results are discussed in relation to contemporary theories of the effects of acquired brain injury on neuromuscular function. The implications of the findings for the treatment of articulatory dysfunction in children with motor speech disorders associated with acquired brain injury are highlighted.

A curious experiment: the paradigm switch from observation and speculation to experimentation, in the understanding of neuromuscular function and disease

The four-link chain of the motor unit represents the contemporary end-point of some two millennia of evolving knowledge in neuroscience. The paradigm shift in neuromuscular epistemology occurred in the mid-17th century. In 1666, the newly graduated Dutch doctor, Jan Swammerdam (1637-1680) published his former investigations of dissected nerve-muscle preparations. These experiments comprised the quantum leap from observation and speculation, to that of experimentation in the field of neuroanatomy and neurophysiology. In what he termed 'A Curious Experiment' he also described the phenomenon of intrinsic muscle excitability - I cannot observe that the muscle in the living animal ever absolutely ceases from all motion. Eighty years later (1752), von Haller demonstrated experimentally that irritability (contractility) was an intrinsic property of all muscular tissue; and distinguished between the sensibility of nerve impulses and the irritability of muscular contraction. This experimental progression from Swammerdam to von Haller culminated in 1850, when Claude Bernard's studies in experimental pharmacology confirmed that muscle was a functional unit, independent of any electrical innervation via its supplying nerve. This account comprises an audit of Swammerdam's work in the perspective of neuromuscular knowledge. (C) 2002 Elsevier Science B.V. All rights reserved.

An augmented Lanczos algorithm for the efficient computation of a dot-product of a function of a large sparse symmetric matrix

The Lanczos algorithm is appreciated in many situations due to its speed. and economy of storage. However, the advantage that the Lanczos basis vectors need not be kept is lost when the algorithm is used to compute the action of a matrix function on a vector. Either the basis vectors need to be kept, or the Lanczos process needs to be applied twice. In this study we describe an augmented Lanczos algorithm to compute a dot product relative to a function of a large sparse symmetric matrix, without keeping the basis vectors.

EMA analysis of tongue function in children with dysarthria following traumatic brain injury

Primary objective : To investigate the speed and accuracy of tongue movements exhibited by a sample of children with dysarthria following severe traumatic brain injury (TBI) during speech using electromagnetic articulography (EMA). Methods and procedures : Four children, aged between 12.75-17.17 years with dysarthria following TBI, were assessed using the AG-100 electromagnetic articulography system (Carstens Medizinelektronik). The movement trajectories of receiver coils affixed to each child's tongue were examined during consonant productions, together with a range of quantitative kinematic parameters. The children's results were individually compared against the mean values obtained by a group of eight control children (mean age of 14.67 years, SD 1.60). Main outcomes and results : All four TBI children were perceived to exhibit reduced rates of speech and increased word durations. Objective EMA analysis revealed that two of the TBI children exhibited significantly longer consonant durations compared to the control group, resulting from different underlying mechanisms relating to speed generation capabilities and distances travelled. The other two TBI children did not exhibit increased initial consonant movement durations, suggesting that the vowels and/or final consonants may have been contributing to the increased word durations. Conclusions and clinical implications : The finding of different underlying articulatory kinematic profiles has important implications for the treatment of speech rate disturbances in children with dysarthria following TBI.

Perceptual and instrumental analysis of laryngeal function after traumatic brain injury in childhood

Objective: To investigate laryngeal function and phonatory disturbance in children with traumatic brain injury (TBI), using both perceptual and instrumental techniques. Design and participants: The performance of 16 individuals with moderate to severe TBI acquired in childhood and 16 nonneurologicatly impaired control subjects was compared on a battery of perceptual (Frenchay Dysarthria Assessment, speech sample analysis) and instrumental (Aerophone II, laryngograph) assessments. Results and conclusions: As a group, the children with TBI demonstrated normal, or only minimally impaired laryngeal function, when compared with the control group, which contrasts with the significant laryngeal impairment noted in adults after TBI. Several reasons for the different findings in relation to laryngeal function in adults and children after TBI are postulated: (1) differing types of injury usually incurred by adults and children may result in a relatively decreased degree of neurologic impairment in these children, (2) differences in recovery potential between adults and children, and (3) the pediatric larynx is still developing, hence it may be better able to compensate for any impairment incurred.

Tissue Doppler imaging for evaluation of myocardial function in patients with diabetes mellitus

Purpose of review Heart failure and diabetes mellitus are frequently associated, and diabetes appears to potentiate the clinical presentation of heart failure related to other causes. The purpose of this review is to examine recent advances in the application of tissue Doppler imaging for the assessment of diabetic heart disease. Recent findings Recent studies have documented that both myocardial systolic and diastolic abnormalities can be identified in apparently healthy patients with diabetes and no overt cardiac dysfunction. Interestingly, these are disturbances of longitudinal function, with compensatory increases of radial function-suggesting primary involvement of the subendocardium, which is a hallmark of myocardial ischemia. Despite this, there is limited evidence that diabetic microangiopathy is responsible-with reduced myocardial blood volume rather than reduced resting flow, and at least some evidence suggesting a normal increment of tissue velocity with stress. Finally, a few correlative studies have shown association of diabetic myocardial disease with poor glycemic control, while angiotensin converting enzyme inhibition may be protective. Summary Tissue Doppler imaging (and the related technique of strain rate imaging) appears to be extremely effective for the identification of subclinical LV dysfunction in diabetic patients It is hoped that the recognition of this condition will prompt specific therapy to prevent the development of overt LV dysfunction.

Assessment of diastolic function: What the general cardiologist needs to know

Diastolic dysfunction has a major impact on symptom status, functional capacity, medical treatment, and prognosis in both systolic and diastolic heart failure (HF), irrespective of the cause.w1 w2 When systolic dysfunction is clearly present, the central clinical question concerns the presence or absence of elevated filling pressure; a restrictive filling pattern is highly specific for elevated pulmonary wedge pressure in this setting.1w3 The transmitral flow pattern is also predictive of outcome; non-reversibility of restrictive filling with treatment portends a very poor prognosis.2 Thus, diastolic evaluation is an important component of the evaluation of the patient with systolic left ventricular (LV) impairment.