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Biomedical subjects

J G Phillips

Publications and source records attributed to J G Phillips.

At least 19 recordsLinked to original sources
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

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

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↗
PubMed1992

Initiation and execution of movement sequences in those suffering from and at-risk of developing Huntington's disease.

Recent research has shown that Huntington's disease (HD) causes problems in the initiation and execution of movement (akinesia, bradykinesia): information which is useful in documenting the functional progression of the disease. The present experiment used a sequential movement task to characterize such impairments. Eighteen patients diagnosed as suffering from HD, and a similar number of matched At-Risk (AR) and Normal control subjects, performed sequential button pressing tasks, under varying amounts of visual advance information. Specific dimensions of motor control were examined (hand, direction). Movement initiation and in particular movement duration were useful indicators of the functional progression of the disease, and also detected anomalies of performance in some AR individuals. Impaired motor programming was indicated by patients' difficulty in initiating movements in the absence of external visual cues, and their problems in utilizing advance information to control movement. Patients had specific deficits in initiating movements with the nonpreferred hand, and directional movement asymmetries were accentuated. The results suggest that HD causes difficulties at three discrete levels: in utilizing advance information, in the initiation and in the spatial representation of movement.

Adult↗
PubMed1992

Programming of single movements in Parkinson's disease: comparison with Huntington's disease.

The preparation of individual finger movements was examined in Parkinson's disease (PD), in comparison with a similar study of Huntington's disease (HD). Motor programming was varied by increasing the amount of information available in advance of each movement. PD patients had particular difficulty when there was no cue light in advance of the movement, and when two upcoming movements were cued ahead of the current movement. Such difficulties suggest that PD patients may have difficulty in performing movements without sensory cuing, and in maintaining and organising a future sequence of movements. HD patients had been previously shown to have similar deficits. Commonalities in these once contrasted disorders probably arise from disruption of common mechanisms.

Adult↗
PubMed1992

Impairments of movement initiation and execution in unilateral neglect. Directional hypokinesia and bradykinesia.

Patients with unilateral neglect may exhibit slowness in the initiation of contralesionally directed movements in peripersonal space (directional hypokinesia). The present study used a sequential movement task to characterize any such impairment in a group of 24 patients with right hemisphere lesions, 18 of whom had left neglect. A further five patients with left hemisphere lesions, one of whom had right neglect, were also tested. We measured movement initiation and execution times for leftward and rightward movements in either hemispace and across the body midline. Most left neglect patients, particularly those with lesions involving posterior cortex, showed directional hypokinesia. Left neglect patients with anterior and/or subcortical lesions also showed directional bradykinesia, i.e. a slowing in the execution phase of contralesionally directed movements. This impairment occurred regardless of the spatial location of the apparatus and was exacerbated as patients moved closer to their neglected side. The patient with right neglect showed directional hypokinesia but not directional bradykinesia. Right hemisphere and left hemisphere lesion patients without neglect performed in a manner comparable to controls, who did not exhibit directional hypokinesia or directional bradykinesia. These results suggest that directional hypokinesia is associated with both left hemisphere and right hemisphere damage, but only in the context of unilateral neglect. Moreover, the site of hemispheric lesion may determine the temporal characteristics of movement impairments in neglect. Damage to posterior cortex produces deficits in detecting contralesional targets and initiating movements toward them, while damage to anterior or subcortical structures may disrupt the internal representation of an intended trajectory.

Adult↗
PubMed1992

Impairment in bilateral alternating movements in Parkinson's disease?

Although problems in bilateral simultaneous movements in Parkinson's disease (PD) are well known, such deficits have not been reported to be any more impaired than simultaneous movements within the same limb. This is surprising, since (a) the parallels between supplementary motor area (SMA) damage and PD are well documented and (b) the SMA seems to play a special role in bilateral motor control. Bilateral versus unilateral movements in PD were examined by using a task that compared alternating movements of fingers of the same hand with alternating movements of fingers of the opposite hands. PD patients showed particular problems in programming and transferring motor activity to fingers on the opposite side of the body, as opposed to switching motor activity between fingers on the same side of the body. These findings outline the relevance of SMA dysfunction to PD.

Aged↗
PubMed1991

Lack of ranitidine effects on cyclophosphamide bone marrow toxicity or metabolism: a placebo-controlled clinical trial.

We previously reported that cimetidine but not ranitidine significantly enhances cyclophosphamide-induced bone marrow toxic effects and the appearance of cyclophosphamide alkylating species in a murine leukemia mouse model, and we advised caution in the use of cimetidine with microsomally metabolized anticancer drugs. Both drugs have been used for the treatment of gastric complications of chemotherapy. Using a randomized, double-blind, crossover study design, we have now evaluated the potential interaction of ranitidine with cyclophosphamide in seven cancer patients, who received two courses of cyclophosphamide, one with ranitidine and one with placebo. Four patients received ranitidine in the first course, and three received placebo. Ranitidine or placebo was started 3 days before a single dose of cyclophosphamide and given for 17 consecutive days. Ranitidine or placebo was given orally (300 mg/d), and cyclophosphamide (600 mg/m2) was given intravenously with [3H]cyclophosphamide (1000 muCi). Cyclophosphamide treatment was repeated at 4 weeks plus or minus 4 days. Blood samples were collected at intervals from 5 minutes to 24 hours after cyclophosphamide treatment and analyzed by thin-layer chromatography and radioassay for the drug and its metabolites. On days 0, 7, 14, and 21 after cyclophosphamide administration, complete blood cell counts, white blood cell differential counts, platelet counts, and SMA-17 were determined. The differences in mean nadir white blood cell counts, granulocyte counts, hemoglobin levels, and hematocrit values during ranitidine versus placebo treatment were not statistically significant. In a statistical but not a clinical sense, mean nadir platelet counts were significantly lower with ranitidine. There was a statistically significant increase in area under the curve for drug concentration in plasma x time (AUC) with ranitidine as well as a statistically significant decrease in the total-body clearance rate of the cyclophosphamide molecule. However, the effect on AUC for the major oncolytic metabolites 4-hydroxycyclophosphamide and phosphoramide mustard was not statistically significant. The lack of toxicologic or metabolic interaction between ranitidine and cyclophosphamide suggests that ranitidine can be used safely with cyclophosphamide.

Adult↗
PubMed1991

Fate of unirradiated Salmonella in irradiated mechanically deboned chicken meat.

Mechanically deboned chicken meat was irradiated at 0, 1.25 and 2.50 kGy (Cesium 137) and inoculated with Salmonella dublin ATCC 15480, Salmonella enteritidis ATCC 9186 or Salmonella typhimurium ATCC 14028. Samples were then stored at 5 degrees C and 10 degrees C and were subjected to microbiological analysis directly after irradiation and inoculation (time 0), and after 24, 72, 120, 168 and 216 h of storage. Samples stored at 20 degrees C were examined at time 0 and after 6, 12 and 24 h of storage. Irradiation at 1.25 and 2.50 kGy caused an average reduction in bacterial levels of 2.23 and 3.44 logs, respectively. S. dublin, S. enteritidis and S. typhimurium showed very small, insignificant changes in numbers, during storage of meat for 9 days at 5 degrees C. The final populations of S. dublin and S. typhimurium in samples irradiated before inoculation and stored at 10 degrees C or 20 degrees C were greater than the equivalent populations in samples which had not been irradiated before inoculation. Reduction of indigenous microflora in mechanically deboned chicken meat by irradiation may create better conditions for the growth of salmonellae and may thus increase the risk of salmonellosis when accidental contamination and temperature abuse occur after a radiation treatment. Therefore, irradiated mechanically deboned chicken meat should be properly refrigerated and protected against contamination.

Aerobiosis↗
PubMed1991

A drape for temporomandibular joint surgery.

A method for draping in TMJ surgery including arthroscopy is presented using a urological drape. The advantage is that it allows movement of the mandible by the surgeon or assistant without their contamination by saliva.

Humans↗
PubMed1991

Reconstruction of the defect at the donor site of the temporalis muscle flap.

A method for the immediate correction of the defect created at the donor site of the temporalis muscle flap is described. It uses a performed acrylic prosthesis. A case is presented in which the prosthesis could have been used to good effect, and two cases are reported to show the successful use of this technique.

Acrylic Resins↗
PubMed1991

Laboratory biology of Ornithodoros (Alectorobius) puertoricensis (Acari: Argasidae).

The laboratory biology of Ornithodoros (Alectorobius) puertoricensis Fox was studied over a 2-yr period. Approximately 100-150 ticks were reared individually at each of four temperatures: 22, 27, 33, and 40 degrees C and 90-95% RH. The mean egg incubation periods at those temperatures were 20.3, 11.1, 7.3, and 6.1 d, respectively. The average larval feeding period was 5.8 +/- 1.5 d for 15,875 larvae that fed on guinea pigs. The development times for first to fourth nymphal instars were as follows: 11.7, 48.5, 75.1, and 92.1 d, respectively, at 22 degrees C; 5.8, 18.8, 38.0, and 36.0 d, respectively, at 27 degrees C; 4.2, 10.5, 14.9, and 38.1 d, respectively, at 33 degrees C; and 5.8, 10.7, 21.2, and 35.3 d, respectively, at 40 degrees C. Males usually eclosed after three or four molts, and females usually eclosed after four or five molts. Approximately 10% of all nymphs required more than one blood meal per instar at least once during development. Twenty pairs of adults were held at each of three temperatures (22, 27, and 33 degrees C) for a year to study reproductive behavior. The number of gonotrophic cycles per female per year was 6.9, 9.8, and 10.8 at 22, 27, and 33 degrees C, respectively. The mean duration of the gonotrophic cycle was 42.3 d at 22 degrees C, 25.5 d at 27 degrees C, and 20.5 d at 33 degrees C. Mean egg production per female per gonotrophic cycle was 151 at 22 degrees C, 117 at 27 degrees C, and 130 at 33 degrees C and was not affected by temperature. O. puertoricensis did not exhibit autogeny or parthenogenesis. Hyperparasitism was observed in immatures and adults.

Animals↗
PubMed1991

Movement disorders--limb movement and the basal ganglia.

The primary concern of this article is to review experimental methods that may lead to a better understanding of the functional role of the basal ganglia in the control of movement. Two models of basal ganglia impairment are considered: Parkinson's disease and Huntington's disease. The review focuses primarily on akinesia and bradykinesia because they are key abnormalities of basal ganglia dysfunction. In general, through electromyography and kinematic analysis of movement, it may be possible to characterize specific movement disorders. Specifically, if damage sustained by the central nervous system is traced to a certain structure, it may provide insight on the extent of involvement and functional role of that structure in the control of movement. Much of the data reviewed suggests that the basal ganglia may play a specific role in the initiation and regulation of force control.

Basal Ganglia↗
PubMed1989

Visuo-spatial processing in parkinsonians.

It has been suggested that patients with Parkinson's disease (PDs) may have problems processing visuo-spatial information and that this deficiency may contribute to the motor control problems observed in PD. However, most studies reporting visuo-spatial deficits are equivocal; they confound perceptual and motor processes. To address this issue, the present experiment systematically compared the relative contributions of several cognitive processes to performance: perception, stimulus-response translation, movement preparation and execution. Seven non-demented PDs and seven age-matched controls performed visual RT tasks, based upon judgements of spatial displacements. Both the RT and MT data suggested that PDs do not prepare movements as adequately as normals, and that PD deficits are associated with problems controlling movement execution. On the other hand, PDs were not slower in judging distances and linking perception to action, suggesting that previous findings of visuo-spatial deficits may be due in part to motor impairments.

Aged↗
PubMed1989

Effect of gamma irradiation on the B vitamins of pork chops and chicken breasts.

A study was made of the effect of low-dose gamma irradiation on the content of thiamine (B1), riboflavin (B2), niacin, pyridoxine (B6) and cobalamin (B12) in pork chops, and thiamine, riboflavin and niacin in chicken breasts. Gamma irradiation from a caesium-137 source was used to irradiate the samples in a range of 0.49 to 6.65 kGy from -20 to +20 degrees C. Over the range of dose and temperature studied it was possible to derive a mathematical expression for predicting the losses. A calculation was made of the effect of the loss of thiamine, riboflavin and niacin due to irradiation on the overall loss of these vitamins in the American diet. The losses of riboflavin and niacin were of the order of a fraction of a per cent. Pork is an important source of thiamine, but the calculated loss at 1.0 kGy of this vitamin in cooked pork was only 1.5 per cent. There were initial increases with radiation doses up to 2-4 kGy in the measured concentrations of riboflavin and niacin in both pork and chicken. The increases were highly significant, and are of concern both to the study of radiation effects and the chemical method of the determination of these two vitamins.

Animals↗
PubMed1989

Thrombolysis with systemically administered t-PA in a new venous thrombosis model.

Early thrombosis of either the arterial or venous supply of a free flap or island pedicle flap results in total flap necrosis. Until very recently, the only option for flap salvage was surgical intervention and, often, revision of the vascular pedicle. Current advances in the pharmacologic treatment of coronary artery and deep leg vein thrombosis have kindled interest in the field of reconstructive surgery for pharmacologic treatment of thromboses that compromise flaps. In the past, there has been research on the local and systemic administration of thrombolytic agents for lysis of experimentally induced thrombi in various animal models. A new venous inversion graft thrombosis model is presented here, which possesses many advantages over previously employed research models. This study demonstrates thrombolysis with systemically administered tissue plasminogen activator (t-PA) in this model.

Animals↗