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Biomedical subjects

Richard D Jones

Publications and source records attributed to Richard D Jones.

16 recordsLinked to original sources
PubMed2003

Tics and developmental stuttering.

BACKGROUND: Developmental stuttering affects 1% of the population but its cause remains unclear. Recent PET studies of metabolism in the central nervous system suggest that it may be related to dysfunction in the basal ganglia or its connections with regions of the cortex associated with speech and motor control. OBJECTIVE: To determine the presence and characteristics of involuntary movements (IMs) in people who stutter and to investigate the hypothesis that these movements may be of a very similar nature to the IMs seen in patients with movement disorders due to basal ganglia dysfunction. METHODS: Sixteen adults with developmental stuttering and 16 controls matched for sex and age were audio-videotaped while freely speaking 300 words in conversation and reading aloud 300 words. The audio data was inspected for dysfluencies and the video data was scrutinised for the presence and characteristics of IMs. RESULTS: Subjects who stuttered produced more IMs than controls during free speech (354 vs 187, p<0.05) and reading (297 vs 47, p<0.001). Most of the IMs in both groups were tics, with a greater number of both simple and complex motor tics (CMTs) in subjects who stuttered. CMTs were more frequent than simple motor tics in those who stuttered, but not in controls. The combination of repetitive eye blink followed by prolonged eye closure was found exclusively in the stuttering group, as were simple tics consisting of eyebrow raise or jaw movement. Dystonia in the form of blepharospasm was identified in a small number of subjects who stuttered. Choreic movements were not associated with stuttering. CONCLUSIONS: Developmental stuttering is associated with the presence of IMs that are predominantly simple and CMTs. This association suggests that tics and stuttering may share a common pathophysiology and supports the view that, in common with tics, stuttering may reflect dysfunction in the basal ganglia or its immediate connections.

Adolescent↗
PubMed2003

Saccadic suppression of displacement: effects of illumination and background manipulation.

In contrast to other functions which are suppressed during saccades, saccadic suppression of displacement (SSD--a decrease in sensitivity to visual displacements during saccades) has often been considered to be due to efferent processes rather than to visual masking. The aim of this study was to explicitly assess the importance of visual conditions in SSD. In two experiments, a small computer-generated target made random horizontal jumps. An infrared eye tracker was used to detect the saccade toward the new position, triggering a smaller centripetal displacement of the target. Subjects reported awareness of these intrasaccadic displacements by pressing a key. In the first experiment, the task was performed in both a well-lit environment and in darkness. In the second experiment these conditions were replicated and additional factors such as the contrast of the background and the effect of moving the target spot alone or the target plus the entire background were investigated. Unlike other forms of saccadic suppression, SSD was stronger in the dark, although subjects also had a greater bias to report detections in that condition. Other background manipulations had no effect. The effect of ambient lighting on SSD is small and subtle. Effects of other background manipulations may be overridden by the focusing of attention on a small moving target.

Adolescent↗
PubMed2003

The effects of alcohol on driving-related sensorimotor performance across four times of day.

OBJECTIVE: The effect of alcohol on driving-related tracking tasks at four times of day was examined to address concerns that the legal driving alcohol threshold in New Zealand (80 mg/dl blood) may have greater effects during the early afternoon and early morning than during the evening and midmorning. METHOD: A volunteer group of 16 male army personnel provided a homogenous sample with respect to time-of-day characteristics. After a formal practice session, members of the sample performed lateral (one-dimensional) tracking tasks in eight counterbalanced sessions, either with or without alcohol (0.836 g/kg), at 0900, 1300, 1800 and 0100 hours. The tasks varied in terms of smooth and ballistic motor pursuit, unpredictability and availability of target preview. RESULTS: Alcohol markedly impaired tracking accuracy (error from target), especially in nonpreview conditions. The only evidence for an overall time-of-day effect was on a ballistic pursuit nonpreview task, but there was no indication of any alcohol by time-of-day interactions. CONCLUSIONS: When tested 30 minutes after consumption of alcohol, sensorimotor tracking skills are markedly impaired at alcohol levels approaching the New Zealand threshold for legal driving, but these effects are not subject to circadian variations.

Adult↗
PubMed2003

Altered circulating hormone levels, endothelial function and vascular reactivity in the testicular feminised mouse.

OBJECTIVE: Testicular feminised (Tfm) mice express a non-functional androgen receptor, and also have reduced levels of circulating testosterone. Recent studies support a cardio-protective role for testosterone since it elicits systemic and pulmonary vasodilatation. The aim of the present study was to determine whether androgen insensitivity and hypotestosteronaemia in the Tfm mouse are associated with abnormal vascular reactivity or hormone status. METHODS: Adult male Tfm and littermate control mice were killed and the blood collected. Femoral (diameter range = 183-508 microm) and pulmonary (diameter range = 320-816 microm) arteries were dissected and loaded in either a wire or pressure myograph, at 100 mmHg or 17.5 mmHg respectively. Pharmacological assessment of the vasoreactivity to potassium chloride (KCl, 80 mmol/l) and either noradrenaline (NA, 1 nmol/l-100 micromol/l) and acetylcholine (ACh, 0.1-100 micromol/l) or testosterone (1 nmol/l-100 micromol/l) was then made. RESULTS: Tfm mice had reduced levels of testosterone (1.8+/-0.3 nmol/l) compared with controls (9.3+/-2.0 nmol/l, P<0.001) and elevated levels of cholesterol (3.6+0.1 mmol/l) compared with controls (3.2+0.1 mmol/l, P<0.05). Femoral arteries from Tfm mice exhibited reduced vasoconstriction to 80 mmol/l KCl (3.27+/-0.23 mN/mm) compared with vessels from controls (4.44+/-0.41 mN/mm, P<0.05), and reduced endothelial-dependent vasodilatation to 0.1-100 micromol/l ACh (23.3+/-3.6% relaxation) compared with vessels from controls (41.6+/-5.4% relaxation, P<0.05). Vasoconstriction to NA (1 nmol/l-100 micromol/l) and vasodilatation to testosterone were unaffected. CONCLUSIONS: Androgen receptor deficiency and hypotestosteronaemia in the Tfm mouse reduced endothelial function and impaired voltage-operated calcium channel activity, which may pre-dispose to cardiovascular disease. Testosterone-induced vasodilatation was unaffected, demonstrating no involvement of the androgen receptor in this response.

Androgen-Insensitivity Syndrome↗
PubMed2002

Saccadic adaptation in neurological disorders.

The role of saccadic adaptive processes in recovery from the effects of various neurological disorders, such as myasthenia gravis, extraocular muscle palsies, and age-related macular degeneration, is reviewed. Studies of clinical populations (e.g. cerebellar disease, mild closed head injury, and opsoclonus) in which intrasaccadic displacement of visual targets has been used to stimulate adaptation are also reviewed. Our own data from such a study of 12 subjects with Parkinson's disease are presented, showing that visually guided adaptation is preserved in PD while memory-guided adaptation is impaired. This supports a model in which different brain regions subserve adaptation in different tasks.

Adaptation, Physiological↗
PubMed2002

Visuoperceptual and visuomotor deficits in developmental stutterers: an exploratory study.

Although the cause of stuttering is unknown, there is strong evidence for it being a neuromotor disorder characterised by an abnormality of higher control encompassing not only speech but other motor systems. The aim of this exploratory study was to look for the presence of non-speech/language deficits--in particular, visuomotor and visuoperceptual deficits--in persons who stutter. Twelve moderate to severe developmental stutterers were compared with a group of fluent speakers, matched for age and sex, on a range of computerized sensory-motor tasks. These tasks covered various aspects of visuomotor function--ballistic movement, dynamic steadiness, and several types of tracking--and visuoperceptual function--acuity, static perception, and dynamic perception. A novel technique was used to remove the visuospatial component from tracking performance. Stutterers had slower reaction times, less accurate random tracking, and impaired dynamic visual perception. Severity of stuttering correlated with reaction time and dynamic perception. Removal of the visuoperceptual component from tracking performance indicated that the impaired tracking in the stutterers was predominantly due to reduced dynamic perception. This is the first study to provide preliminary evidence for the presence of non-linguistic visuoperceptual and upper-limb visuomotor tracking deficits in people with moderate to severe stuttering. These findings support a neurogenic aetiology for stuttering and are compatible with evidence of an overactive dopamine system in stutterers.

Adult↗
PubMed2002

Heart failure as an inflammatory condition: potential role for androgens as immune modulators.

Heart failure has traditionally been considered a disease of the myocardium, with symptoms arising from altered haemodynamics. However, it is now recognised that, in addition to marked neuroendocrine disturbance, there is perturbation of cytokine expression in patients with heart failure, resulting in an inflammatory imbalance. This not only influences symptoms, but also plays a central role in the underlying pathophysiological processes of heart failure, leading to disease progression and poorer prognosis. Recognition of the influence of cytokines, in particular tumour necrosis factor, has opened a new avenue for potential therapies for heart failure. Current approaches involve immunomodulation, aimed at suppressing tumour necrosis factor. We suggest that androgens may potentially offer a superior therapeutic strategy by their well-recognised non-specific immunosuppressive and anti-inflammatory effects. Studies of cell lines, human mononuclear cells and animals in vivo have demonstrated the 'anti-cytokine' actions of androgens, and we have found a similar action in whole blood from patients with heart failure. These effects, along with the anabolic action of these agents, make androgens an attractive potential option for treatment of patients with heart failure.

Androgens↗
PubMed2002

Factors influencing the use of thoracic radiotherapy in lung cancer--an analysis of the 1995 Scottish lung cancer audit.

AIMS: To determine the frequency of delivery of thoracic radiotherapy (TRT) to patients with lung cancer in Scotland in 1995, and identify patient, disease and process variables affecting the probability of receiving TRT. METHODS: Retrospective case note audit of all patients with lung cancer diagnosed in Scotland in 1995. RESULTS: 1118 (30.8%) of 3,855 patients diagnosed with lung cancer in Scotland in 1995 for whom the medical records could be traced received TRT. In those who did not have small cell lung cancer, multivariate analysis indicated that diagnosis by a lung cancer specialist, clinical extent of disease and microscopic verification of cancer (all P<0.0001) and age (P=0.0005) were associated with an increased chance of receiving TRT. There was also a wide variation between different Health Boards (HB) of residence in the proportion of patients receiving TRT (P<0.0001). There was no association between the presence of local symptoms (cough, chest pain or haemoptysis) and the delivery of TRT. Of 351 patients with limited stage small cell lung cancer, 51 (14.5%) received chemotherapy and TRT, and 19 (5.4%) chemotherapy and cranial irradiation. CONCLUSIONS: TRT was delivered to fewer than one-third of patients with lung cancer in Scotland in 1995. This is lower than reported in other international audits. The chance of receiving TRT seemed to be associated with service issues rather than clinical need.

Aged↗
PubMed2002

Adaptive modification of saccade amplitude in Parkinson's disease.

The accuracy of saccades (fast eye movements) is maintained over time and is an adaptive ability usually ascribed to the cerebellum. Adaptation might occur elsewhere in certain tasks, such as in the prefrontal cortex for memory-guided saccades. We hypothesized that adaptation of memory-guided saccades would be impaired in Parkinson's disease, as basal ganglia dysfunction can disrupt the operation of the prefrontal cortex, while adaptation of visually guided saccades would be preserved. Adaptation was induced by consistently yet imperceptibly displacing targets as saccades were made toward them, causing artificial saccadic inaccuracy. Twelve Parkinson's disease subjects (OFF medication) and 12 age-matched controls performed 245 visually- and memory-guided horizontal saccades in separate sessions. An infrared eye tracker detected the saccade, during which the target was displaced by 12.5% of the size of the initial jump, either in the same (centrifugal) or the opposite (centripetal) direction. Parkinson's disease subjects made smaller visually guided saccades than did controls [F(1,20) = 9.10, P < 0.01], yet both groups modified saccade size appropriately. Parkinson's disease memory-guided saccades were also smaller than those of controls [F(1,19) = 5.93, P < 0.05]. While controls decreased (by 8.6%) or increased (by 4.1%) the size of these saccades appropriately, Parkinson's disease subjects decreased saccade size in response to both centripetal adaptation (by an excessive 18.3%) and centrifugal adaptation (by 3.5%). Parkinson's disease subjects were less able to modify saccadic size appropriately when the movement size was specified in motor memory: a predilection for excessive hypometria was invoked, regardless of adaptation direction. This indicates that, in certain tasks, saccadic adaptation involves structures other than the cerebellum.

Adaptation, Physiological↗
PubMed2002

Pulmonary vasodilatory action of testosterone: evidence of a calcium antagonistic action.

Recent evidence supports a beneficial effect of testosterone on the cardiovascular system. Testosterone acts as a coronary vasodilator and reduces myocardial ischemia in men with coronary heart disease. The aim of the current study was to determine whether testosterone has a similar vasodilatory action in the pulmonary circulation and to characterize the underlying mechanism of action. The vasodilatory action of testosterone was studied in pulmonary arteries (n = 132, mean internal diameter = 344 +/- 8 microm) isolated from male rats (n = 48, mass = 396 +/- 7 g) mounted in a small vessel wire myograph and loaded to a tension equivalent to 17.5 mm Hg. Micromolar concentrations of testosterone induced dilatation in pulmonary arteries preconstricted with prostaglandin F2alpha (100 microM) within seconds of application. Dilatation to testosterone was similar in vessels treated with N-gamma-nitro-l-arginine methyl ester (l-NAME) (10 microM) or vehicle (5 microl distilled water), -38.2 +/- 2.9%, and -38.1 +/- 3.4%, respectively, and in vessels treated with indomethacin (10 microM), flutamide (10 microM), or vehicle (5 microl ethanol), -35.5 +/- 2.8%, -43.2 +/- 3.6%, and -35.7 +/- 4.6%, respectively (all p > 0.05). Maximal dilatation to testosterone occurred following preconstriction with agents that activated voltage-gated calcium channels such as prostaglandin F2alpha (-34.6 +/- 5.0%), BAY K8644 (-32.9 +/- 8.7), or potassium chloride (-26.7 +/- 1.5%), compared with calcium-independent protein kinase C activation by phorbol dibutyrate (-14.7 +/- 1.6%) or capacitative calcium entry via thapsigargin (-5.1 +/- 0.9%). This study demonstrates that testosterone induces pulmonary dilatation via a mechanism that is independent of the classic androgen receptor and also of the release of nitric oxide or dilator prostaglandins. The data support a calcium antagonistic action for testosterone in the pulmonary circulation, primarily against voltage-gated calcium channels.

Animals↗
PubMed2002

Simulating closed- and open-loop voluntary movement: a nonlinear control-systems approach.

In many recent human motor control models, including feedback-error learning and adaptive model theory (AMT), feedback control is used to correct errors while an inverse model is simultaneously tuned to provide accurate feedforward control. This popular and appealing hypothesis, based on a combination of psychophysical observations and engineering considerations, predicts that once the tuning of the inverse model is complete the role of feedback control is limited to the correction of disturbances. This hypothesis was tested by looking at the open-loop behavior of the human motor system during adaptation. An experiment was carried out involving 20 normal adult subjects who learned a novel visuomotor relationship on a pursuit tracking task with a steering wheel for input. During learning, the response cursor was periodically blanked, removing all feedback about the external system (i.e., about the relationship between hand motion and response cursor motion). Open-loop behavior was not consistent with a progressive transfer from closed- to open-loop control. Our recently developed computational model of the brain--a novel nonlinear implementation of AMT--was able to reproduce the observed closed- and open-loop results. In contrast, other control-systems models exhibited only minimal feedback control following adaptation, leading to incorrect open-loop behavior. This is because our model continues to use feedback to control slow movements after adaptation is complete. This behavior enhances the internal stability of the inverse model. In summary, our computational model is currently the only motor control model able to accurately simulate the closed- and open-loop characteristics of the experimental response trajectories.

Adaptation, Biological↗
PubMed2002

Intrinsic responses of rat coronary arteries in vitro: influence of testosterone, calcium, and effective transmural pressure.

Administration of testosterone to men with angina has been shown to reduce myocardial ischemia. The mechanism of this effect is not clear but could be via an influence on coronary artery tone. We therefore employed an animal model to study the intrinsic responses of coronary arteries mounted in the wire myograph and evaluated the effect of testosterone on coronary artery tone in vitro. Intrinsic responses of the vessels and response to addition of testosterone were observed. Immediately after loading, vessels relaxed, an effect that was dependent on the baseline transmural pressure of vessels and was attenuated by pretreatment with N-nitro-L-arginine methyl ester. Subsequent contraction to a peak wall tension (intrinsic tone) was abolished by removal of extracellular calcium. Addition of testosterone produced a significant dose-dependent relaxation of intrinsic tone in all groups studied. The lowest concentration at which relaxation occurred was 10-6M. We conclude that rat coronary arteries exhibit calcium-dependent intrinsic responses and develop spontaneous tone. Furthermore, addition of testosterone reduces intrinsic coronary artery tone. These findings may have important implications for men with angina and low plasma testosterone levels.

Animals↗
PubMed2002

A laser-based eye-tracking system.

This paper reports on the development of a new eye-tracking system for noninvasive recording of eye movements. The eye tracker uses a flying-spot laser to selectively image landmarks on the eye and, subsequently, measure horizontal, vertical, and torsional eye movements. Considerable work was required to overcome the adverse effects of specular reflection of the flying-spot from the surface of the eye onto the sensing elements of the eye tracker. These effects have been largely overcome, and the eye-tracker has been used to document eye movement abnormalities, such as abnormal torsional pulsion of saccades, in the clinical setting.

Adolescent↗
PubMed2001

Subclavian artery angioplasty for the treatment of angina using a double balloon technique to protect a left internal mammary artery graft.

Percutaneous transluminal angioplasty (PTA) has proven to be a safe and effective method of treating subclavian stenosis with technical success rates ranging from 83 to 100%. This technique, however, can result in distal embolisation. In the presence of a previous internal mammary bypass graft this may prove catastrophic, especially when that graft provides the dominant supply to the heart. Clearly any technique of reducing the risk of graft embolisation is valuable in this small subgroup of patients. The deployment of a double balloon to protect the left internal mammary artery graft to prevent this potentially fatal event has not been described previously.

Angina Pectoris↗