Biomedical subjects

J G Phillips

Publications and source records attributed to J G Phillips.

At least 55 records · Page 3Linked to original sources

PubMed1997

Functional asymmetries in the movement kinematics of patients with Tourette's syndrome.

OBJECTIVES: This study adopted a concurrent task design and aimed to quantify the efficiency and smoothness of voluntary movement in Tourette's syndrome via the use of a graphics tablet which permits analysis of movement profiles. In particular, the aim was to ascertain whether a concurrent task (digit span) would affect the kinematics of goal directed movements, and whether patients with Tourette's syndrome would exhibit abnormal functional asymmetries compared with their matched controls. METHODS: Twelve patients with Tourette's syndrome and their matched controls performed 12 vertical zig zag movements, with both left and right hands (with and without the concurrent task), to large or small targets over long or short extents. RESULTS: With short strokes, controls showed the predicted right hand superiority in movement time more strongly than patients with Tourette's syndrome, who instead showed greater hand symmetry with short strokes. The right hand of controls was less force efficient with long strokes and more force efficient with short strokes, whereas either hand of patients with Tourette's syndrome was equally force efficient, irrespective of stroke length, with an overall performance profile similar to but better than that of the controls' left hand. The concurrent task, however, increased the force efficiency of the right hand in patients with Tourette's syndrome and the left hand in controls. CONCLUSIONS: Patients with Tourette's syndrome, compared with controls, were not impaired in the performance of fast, goal directed movements such as aiming at targets; they performed in certain respects better than controls. The findings clearly add to the growing literature on anomalous lateralisation in Tourette's syndrome, which may be explained by the recently reported loss of normal basal ganglia asymmetries in that disorder.

Adult↗

PubMed1996

Movement-related potentials associated with movement preparation and motor imagery.

Movement-related potentials (MRPs), reflecting cortical activity associated with voluntary movement, typically show a slowly increasing negative potential beginning between 1 and 2 s prior to movement, which most likely reflects motor preparatory processes. Studies of regional cerebral blood flow implicate the supplementary motor area in such preparatory processes; however, the contribution of the supplementary motor area to premovement activity observed in MRPs is debated. It is possible to examine MRPs relating to movement preparation alone, in the absence of movement execution, by recording MRPs associated with imagined movements. In this study, MRPs were recorded from 11 healthy control subjects while performing a sequential button-pressing task in response to external cues, and while imaging performance of the same task in response to the same cues. The early component of MRPs was found not to differ in amplitude, onset time, or topography when performing compared with imagining movement, indicating that both movement execution and motor imagery involve similar pre-movement preparatory processes generated in the same cortical area-most likely the supplementary motor area. It is therefore concluded that the early component of the MRP reflects activity arising pre-dominantly from the supplementary motor area and is associated with pre-movement motor preparatory processes which occur relatively independently of actual movement execution.

Adult↗

PubMed1996

The effect of Huntington's disease and Gilles de la Tourette's syndrome on the ability to hold and shift attention.

Huntington's disease (HD) and Tourette's syndrome (TS) are two basal ganglia (BG) disorders, associated not simply with hyperkinetic movements but also with attentional impairments. The purpose of this experiment was to evaluate the attention deficits reported in HD and TS via the use of a vibrotactile choice reaction time (CRT) procedure involving biased probabilities of event occurrence. We attempted to ascertain whether HD and TS patients are impaired in their ability to shift their attention to an unexpected location, or when they have to hold attention to an expected location. The results demonstrate that HD patients, as compared to controls, experience difficulties in shifting their attention from expected to unexpected spatial locations; this effect was exacerbated with the adoption of a crossed arm configuration. On the other hand, TS patients' performance, although slower overall, was not qualitatively greatly different from that of the controls. We had previously found, with a similar paradigm, that Parkinson's disease patients instead manifest problems in holding or maintaining attention to an expected locus. We conclude that HD patients experience considerable difficulties in allocating attentional resources between expected and unexpected event occurrences. Perhaps due to pervasive subcortical damage and dysfunction in the circuits linking the frontal lobes with the BG. In TS, a similar if milder functional rather than structural deficit may be reflected in a pattern of responses which resembles a weaker version of the HD response pattern.

Adult↗

PubMed1996

Bradykinesia and movement precision in Huntington's disease.

To determine whether bradykinesia in patients with Huntington's disease (HD) reflects impaired force production or an increased requirement for terminal visual guidance, 11 HD patients and matched controls performed drawing movements with varying precision requirements. Participants used an electronic pen upon a WACOM SD420 graphics tablet to join targets of either 10 or 20 mm diameter which were separated by a distance of 62.5 or 125 mm. While HD patients had slower movements, exhibiting more cycles of acceleration and deceleration, patients were not disproportionately affected by variations in target size or separation. Bradykinesia did not seem to be a product of impaired force production or increased reliance upon terminal visual guidance, since neither accelerative or decelerative phases were specifically affected by HD. However, movements of HD patients were of less consistent duration, implying variability associated with internal cues regulating movement.

Adult↗

PubMed1996

Model for the survival of Staphylococcus aureus in nongrowth environments.

A model was developed to estimate the survival times of Staphylococcus aureus in nongrowth environments. A four strain mixture of S. aureus was inoculated into BHI broth that had a lactate buffer with various combinations of pH (3-7) and lactate (0-1%), NaCl (0.5-20%) and NaNO2 (0-200 ppm) and stored at different temperatures (4-42 degrees C). At appropriate times the survivors were enumerated by sampling and spreading on TSA plates. The survival curves were modeled with two forms of a logistic equation and the D values were determined. Polynomial regression equations were then calculated to predict the effect of the environmental factors on the D values. Survival times were increased with higher pH values, lower temperatures, and lower nitrite and lactate concentrations. Added salt increased survival times until the salt concentrations exceeded that of most foods.

Food Microbiology↗

PubMed1996

Visual cues and the handwriting of older adults: a kinematic analysis.

Kinematic techniques determined the nature of any age-related changes in the fluency of handwriting movements and also the extent to which any changes can be related to a differential utilization of visual feedback. To quantitatively document the kinematics of handwriting movements, 24 young and 24 older adults were compared by having them write simple cursive letter ls 4 times on a graphics tablet, under 4 different visual conditions (no vision, non inking pen, inking pen, and lined paper). Pen tip position was sampled at 200 Hz, from which kinematic indexes of movement efficiency and consistency were derived. Quantitative differences in movement trajectories were found in the older adults, who produced less efficient movements with a concomitant increased utilization of external visual cues. Older adults made a differential use of visual feedback to modify movement trajectories, rather than to control the effects of neural noise. Handwriting movements of older adults resembled only to a limited extent those of patients with Parkinson's disease.

Adult↗

PubMed1996

Simon effect and attention in Parkinson's disease: a comparison with Huntington's disease and Tourette's syndrome.

Patients with hyperkinetic basal-ganglia disorders (Huntington's disease, HD; and Tourette's syndrome, TS) have difficulty with spatially incongruent stimulus-response configurations, the Simon effect, and with inhibiting inappropriate responses in a conditionality paradigm. However Parkinson's disease (PD) patients with hypokinetic basal-ganglia disorder show normal (for their age) conditionality and congruency effects, probably because the task is extremely sensitive to aging and PD patients are typically older than HD and TS individuals. Overall, HD patients were by far the most affected, reflecting the likely greater involvement of the caudate (with its predominantly cognitive role) than the putamen; the latter structure, with a predominantly motor involvement, is the more affected in PD.

Aged↗

PubMed1996

Effects of magnetic stimulation over supplementary motor area on movement in Parkinson's disease.

Movement execution can be delayed by transcranial magnetic stimulation delivered over primary motor cortical areas, resulting in transient inhibition of cortico-motor output. Inhibition or disruption of higher-order motor planning and preparatory processes, such as are thought to occur in the supplementary motor area (SMA), would allow an examination of processes at other stages of the motor control system. In this study, six subjects with Parkinson's disease and six healthy control subjects performed a non-cued sequential finger movement task. At various times relative to movement, high-intensity single-pulse magnetic stimulation was delivered over the region of the SMA, with minimal current spread to primary motor areas. When magnetic stimulation was given at early stages during the movement for parkinsonian subjects, movement times were significantly increased, indicating disrupted movements. Supplementary motor area stimulation had no effect when delivered during later stages of the movement or immediately prior to movement onset, and had no apparent effect on control subjects at any time. It is therefore suggested that the SMA is important in motor planning and preparatory processes, since SMA stimulation has no effect on movements in their later stages when planning may be complete, but may disrupt movements in their early stages, when preparation for later stages may still be in progress. Further, possible instability of motor planning/preparation processes in Parkinson's disease is suggested, since these processes appeared more susceptible to disruption by magnetic stimulation in parkinsonian subjects than controls.

Aged↗

PubMed1996

Polypoid scrotal calcinosis: an uncommon variant of scrotal calcinosis.

Scrotal calcinosis is a rare condition characterized by multiple calcified nodules within scrotal skin. To our knowledge, only 67 cases have been reported to date. The etiology has been widely disputed and is viewed by many to be idiopathic. We describe a case of "idiopathic" scrotal calcinosis that not only presents a distinctly unusual clinical appearance, but also shows that at least some cases of this disease occur in association with dystrophic calcification of epidermal (follicular) cysts.

Adult↗

PubMed1995

Reliance on advance information and movement sequencing in Huntington's disease.

To identify the focus of impairment in the performance of sequential movements in Huntington's disease (HD) patients, the extent of their reliance on external advance information was examined. Twelve patients with HD and their age-matched controls performed a series of button-presses at sequential choice points along a response board. A sequential pathway was designated, and with each successive button press, advance visual information was systematically reduced to various extents in advance of each move. HD patients, like previously studied parkinsonian patients, were particularly disadvantaged with high levels of reduction in advance information, and as a consequence, both their initiation and execution of movements progressively slowed with each successive element in the response sequence. The pattern of results was not affected whether or not patients were taking neuroleptic medication, nor did performance on a variety of cognitive measures correlate with motor performance. Control subjects' performance, on the other hand, remained constant in terms of both initiation and execution with each of the three levels of reduction in advance information. We conclude that HD patients, like parkinsonian patients, who also suffer from a basal ganglia (BG) disorder, require external visual cues to sequence motor programs effectively. Our findings suggest that with HD there may be abnormalities in a central mechanism that controls switching between movement segments within an overall motor plan. The BG, which provide internal cues necessary for component sequencing, may be disrupted, thereby impairing the ability to use such internally generated cues to guide movement.

Adult↗

PubMed1995

Impaired movement sequencing in patients with Huntington's disease: a kinematic analysis.

This experiment asked whether Huntington's disease, like Parkinson's disease, another disorder of the basal ganglia, causes a specific progressive deficit in the performance of sequential movement. Ten patients with Huntington's disease and their age-matched controls wrote the lower-case letter "l" four times in a linked cursive script, upon a graphics tablet which sampled pen position at 200 Hz. Kinematic features of sequential movement (stroke length, stroke duration, peak velocity, time to peak velocity and time from peak to zero velocity) were examined in a Group by Stroke Position (2 x 8) design, to identify which aspects of movement might show progressive disturbances. Unlike Agostino et al. [Brain 115, 1481-1495, 1992], this experiment did in fact find progressive changes in the performance of sequential movements. Kinematic analysis indicated a progressive increase in movement duration during sequential movement, that was associated with the accelerative phase of movement.

Adult↗

PubMed1995

Contingent and non-contingent auditory cueing in Parkinson's disease.

Parkinson's disease (PD) patients and their normal controls performed two experiments involving a sequential movement task, depressing a series of buttons at choice points along a response board. Visual or auditory cues were presented prior to each move according to various contingencies. PD, a disorder characterised by degeneration of the basal ganglia (BG), typically manifests with poor execution of motor sequences. We found that external cueing facilitated motor sequencing in PD patients. In particular, auditory cues which occurred late in the movement cycle maximally facilitated switching between subcomponents of a sequence. Based on physiological findings reported in the primate literature [Brotchie et al., Brain 114, 1685-1702, 1978; Schultz and Romo, Exp. Brain Res. 1, 363-384, 1992], it is suggested that external cues enhance performance by replacing defective, internally generated cues (discharges) of the BG. This has implications for the use of physical training strategies in the treatment of PD.

Acoustic Stimulation↗

PubMed1995

Movement-related potentials in Parkinson's disease. Presence and predictability of temporal and spatial cues.

Activity of the supplementary motor area may be inferred from movement-related potentials (MRPs) which are associated with the preparation and execution of voluntary, or internally determined movements. Supplementary motor area activity may be abnormal in Parkinson's disease since its major input from the basal ganglia is disrupted. Investigation of the abnormalities in supplementary motor area activity associated with movement deficits in Parkinson's disease may therefore reveal functions of the basal ganglia and the supplementary motor area. Movement-related potentials associated with sequential movements were investigated under various cueing conditions in Parkinson's disease subjects and age-matched controls. In controls, MRPs revealed involvement of the supplementary motor area in movements which can be internally determined (non-cued and externally cued, predictable movements, but not unpredictable movements). In Parkinson's disease, however, the supplementary motor area was only involved in movements which must be internally determined (non-cued movements, but not externally cued movements); therefore impaired internal control mechanisms, operating via the supplementary motor area, are bypassed when external cues are given. As a result, Parkinson's disease patients are more reliant on external cues and are unable to use predictive models to internally guide movement. Supplementary motor area involvement also relied on the predictability (in controls) or presence (in Parkinson's disease) of timing cues and not spatial cues, indicating a role of the supplementary motor area and basal ganglia in the temporal organizations of sequential movement rather than the programming of specific movements. For non-cued movements, abnormalities in MRPs for Parkinson's disease subjects consisted of delayed MRP onset and peak times, and prolonged cortical activity following movement. These observations led to a proposed model of the interaction between the basal ganglia and the supplementary motor area, involving the temporal organization of voluntary and internally determined sequential movements.

Aged↗

PubMed1995

The Simon effect and attention deficits in Gilles de la Tourette's syndrome and Huntington's disease.

Tourette's syndrome and Huntington's disease have long been clinically associated with attentional deficits. In this study, we aimed to determine the nature and quantify the extent of such deficits. A technique was devised to ascertain the efficiency with which Tourette's syndrome and Huntington's disease patients could shift and direct attention away from naturally expected stimulus-response (S-R) linkages. This was done by varying the relationships formed between stimulus and response location. Attentional efficiency was indicated by relative speed of responding to relevant (congruent) and irrelevant (incongruent) stimuli, in a paradigm developed from the Simon effect. There were five conditions progressively increasing in complexity. The stimuli consisted of left and right pointing arrows and, in some cases, various conditionality manipulations were also employed, such that in the presence of a certain symbol (i.e. 'x') the nature of the response had to be reversed, whereas in the presence of an alternative symbol (i.e. '='), the response was compatible with the direction of the arrow. As predicted, Tourette's syndrome and Huntington's disease patients, regardless of medication or depression status and unlike controls, were particularly disadvantaged in responding to various conflicting S-R configurations. Tourette's syndrome and Huntington's disease patients may experience difficulties in making attentional shifts, or in inhibiting inappropriate responses; they may also be more susceptible (than controls) to the conflict that can arise when the spatial code formed for the stimulus is irrelevant for selecting the appropriate response. We conclude that our findings support the notion that cognitive deficits in Tourette's syndrome and Huntington's disease may stem from abnormalities of the major pathways interconnecting the basal ganglia and the frontal lobes.

Adult↗

PubMed1995

Expanded response surface model for predicting the effects of temperatures, pH, sodium chloride contents and sodium nitrite concentrations on the growth rate of Yersinia enterocolitica.

The previously reported data set for the low temperature (5, 12 and 19 degrees C) of Yersinia enterocolitica was expanded to include higher abusive temperature (28, 37 and 42 degrees C). In addition to temperature, the data set included the effects and interactions of pH (4.5-8.5), sodium chloride (0.5-5%) and sodium nitrite (0-200 micrograms ml-1) on the aerobic growth of Y. enterocolitica in brain heart infusion broth. Growth curves were modeled by fitting viable count data to the Gompertz equation. Quadratic models of natural logarithm transformations of the Gompertz B and M values and the derived values for lag phase durations and generation times were obtained using response surface analyses. Predictions based on the models for B and M values were comparable to predictions based on the derived values. These revised models provide an expanded means for rapidly estimating how the bacterium is likely to respond to any combination of the four variables within the specified ranges.

Aerobiosis↗

PubMed1995

Advance information and movement sequencing in Gilles de la Tourette's syndrome.

Tourette's syndrome is a chronic neurological disorder manifested by involuntary motor tics and vocalisations. Because the basal ganglia have been implicated in the pathology underlying Tourette's syndrome, the present two procedures, both involving sequential movements, sought to determine the extent to which patients with Tourette's syndrome were reliant on, and could utilise different levels of advance information. Patients with Tourette's syndrome were found to be more reliant than controls on external visual cues to execute rather than to initiate a motor programme. When there was a high level of reduction in advance information--that is, a visual pathway to be followed was extinguished well in advance of each successive movement--executions progressively slowed as the sequence was traversed. Similarly, if no advance information was provided before each move, movement execution was slower than that of controls. The movement initiation times of patients with Tourette's syndrome were, however, similar to those of controls, as were their movement execution times when advance visual information was available. It seems that patients with Tourette's syndrome, like parkinsonian patients who are known to have a basal ganglia disorder, require external sensory cues to sequence a motor programme effectively. The present study found evidence consistent with the hypothesis that patients with Tourette's syndrome, like patients with Parkinson's disease, may be dysfunctional in internal switching mechanisms. Alternatively, with limited visual guidance, patients with Tourette's syndrome, regardless of medication or depression state, may require more time to plan and programme each next submovement, and under such conditions may require external visual cues to direct attention effectively to given targets. Although the underlying pathogenesis is still speculative, it is concluded that there is much to support the notion that Tourette's syndrome may stem from abnormalities of the major pathways between the basal ganglia and the frontal lobes.

Adolescent↗

PubMed1995

Pharmacological characterization of GT-2016, a non-thiourea-containing histamine H3 receptor antagonist: in vitro and in vivo studies.

GT-2016, a non-thiourea-containing imidazole, has been developed as a histamine H3 antagonist. In vitro and in vivo studies in rats were conducted to characterize receptor selectivity and autoreceptor functionality for GT-2016. GT-2016 demonstrated high affinity (43.8 +/- 3.0 nM) and selectivity for the histamine H3 receptor in vitro. In vivo, GT-2016 (3, 10 and 30 mg/kg i.p. and p.o.) was shown to cross the blood-brain barrier and dose-dependently bind to cortical histamine H3 receptors. GT-2016 induced dose-dependent increases in histamine turnover at concentrations that exhibited significant histamine H3 receptor occupancy. Also, in vivo microdialysis experiments were conducted in awake, freely moving rats treated with GT-2016. GT-2016 (10 and 30 mg/kg i.p.) increased histamine release by approximately 75% above baseline within 1 hr, and elevated histamine release was observed for up to 2.5 hr after the higher dose. In contrast, GT-2016 was devoid of activity on histamine methyltransferase in vitro at concentrations up to 3 microM. Taken together, the results show that GT-2016 crosses the blood-brain barrier, binds to H3 receptors and increases the release of histamine in the cerebral cortex, consistent with blockade of presynaptic H3 autoreceptors. In summary, these findings allowed us to identify and characterize the in vitro and in vivo biochemical properties of a novel H3 receptor antagonist, GT-2016.

Animals↗

PubMed1994

3-(2-(3-Pyridinyl)thiazolidin-4-oyl)indoles, a novel series of platelet activating factor antagonists.

(2RS,4R)-3-(2-(3-Pyridinyl)thiazolidin-4-oyl)indoles represent a new class of potent, orally active antagonists of platelet activating factor (PAF). The compounds were prepared by acylation of the magnesium or zinc salts of substituted indoles with (2RS,4R)-2-(3-pyridinyl)-3-(tert-butoxycarbonyl)thiazolidin-4-oyl chloride. The 3-acylindole moiety functions as a hydrolytically stabilized and conformationally restricted anilide replacement, which imparts a considerable boost in potency to the series. Structure-activity relationships observed for substitution on the indole ring system are discussed. Members of the series compare favorably with other reported PAF antagonists.

Administration, Oral↗