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P D Thompson

Publications and source records attributed to P D Thompson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects.

The aim of this study was to determine whether prolonged, repetitive mixed nerve stimulation (duty cycle 1 s, 500 ms on-500 ms off, 10 Hz) of the ulnar nerve leads to a change in excitability of primary motor cortex in normal human subjects. Motor-evoked potentials (MEPs) generated in three intrinsic hand muscles [abductor digiti minimi (ADM), first dorsal interosseous (FDI) and abductor pollicis brevis (APB)] by focal transcranial magnetic stimulation were recorded during complete relaxation before and after a period of prolonged repetitive ulnar nerve stimulation at the wrist. Transcranial magnetic stimuli were applied at seven scalp sites separated by 1 cm: the optimal scalp site for eliciting MEPs in the target muscle (FDI), three sites medial to the optimal site and three sites lateral to the optimal stimulation site. The area of the MEPs evoked in the ulnar-(FDI, ADM) but not the median-innervated (APB) muscles was increased after prolonged ulnar nerve stimulation. Centre of gravity measures demonstrated that there was no significant difference in the distribution of cortical excitability after the peripheral stimulation. F-wave responses in the intrinsic hand muscles were not altered after prolonged ulnar nerve stimulation, suggesting that the changes in MEP areas were not the result of stimulus-induced increases in the excitability of spinal motoneurones. Control experiments employing transcranial electric stimulation provided no evidence for a spinal origin for the excitability changes. These results demonstrate that in normal human subjects the excitability of the cortical projection to hand muscles can be altered in a manner determined by the peripheral stimulus applied.

Adult↗
PubMed2000

The effect of testosterone on health-related quality of life in elderly males - a pilot study.

OBJECTIVE: To assess the effect of short-term testosterone supplementation on health-related quality of life in elderly males. METHOD: As part of a double-blind, placebo-controlled study, healthy males > or = 65-year-old were randomised to receive a total of four doses of 200 mg testosterone enanthanate (n = 14) or placebo (n = 8) intramuscularly every 2 weeks. Health-related quality of life (HRQOL) was assessed using the Short Form 36-item (SF-36) and Psychological General Well-Being (PGWB) scales, at baseline, week 8 and during therapy withdrawal, 6 weeks after the last dose. RESULTS: The baseline SF-36 scores were similar between the groups in seven domains; only vitality was significantly lower in the placebo group (T: 80.4, P: 65.6; P = 0.007). After the 8-week treatment period and withdrawal phase, SF-36 scores were not significantly different between the groups. The PGWB scores at baseline, on treatment and off treatment were not significantly different between the groups. Moreover, the SF-36 and PGWB scores within each group did not change significantly over time. CONCLUSION: This pilot study suggests that intramuscular testosterone, administered at a dose of 200 mg every 2 weeks, does not affect the HRQOL of elderly males.

Aged↗
PubMed2000

A SPECT study of the anatomy of transient global amnesia.

This report describes single photon emission tomography (SPECT) evidence of transient, relative hypoperfusion of the right basal ganglia and left temporal lobe in a 60-year-old man studied during the acute phase of classical transient global amnesia (TGA). The findings are interpreted in the light of previous reports indicating that involvement of the right hemisphere or both cerebral hemispheres consistently predicts severe retrograde amnesia, in addition to the typical loss of anterograde memory observed during TGA. These deficits involving the right hemisphere and left temporal lobe may reflect disruption of circuits mediating episodic memory retrieval and memory encoding, respectively.

Amnesia, Retrograde↗
PubMed2000

Gender comparison of RPE at absolute and relative physiological criteria.

PURPOSE: The effect of gender on ratings of perceived exertion for the overall body (RPE-O), chest (RPE-C), legs (RPE-L), and arms (RPE-A (ski)) was determined. METHODS: Comparisons were made at, a) absolute oxygen uptake (VO2, L x min(-1); mL x kg(-1) x min(-1)) and heart rate (HR, b x min(-1)) and b) relative VO2 (%VO2max/peak) and HR (% HRmax/peak) reference criteria. Nine male and 10 female subjects were compared using a perceptual estimation paradigm for treadmill (weight bearing), simulated ski (partial weight bearing), and cycle (nonweight bearing) exercise. RPE was determined by the Borg 15-category scale. RESULTS: For each exercise mode, RPE-O, RPE-L, RPE-A (ski), and RPE-C were higher (P < 0.05) in the female than male cohort when compared at submaximal absolute VO2 criteria. RPE did not differ between female and male cohorts when compared at mode specific relative VO2 criteria. Differences in RPE-O, RPE-L, RPE-A (ski), and RPE-C were not found between female and male subjects when comparisons were made at both absolute and relative HR. Responses were consistent for the three exercise modes. CONCLUSION: RPE did not differ between gender when comparisons were made at relativized VO2 and HR reference criteria at exercise intensities between 70 and 90% of mode specific maximal/peak values.

Adult↗
PubMed2000

The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factor IIB.

The human vitamin D receptor (hVDR) is a ligand-regulated transcription factor that mediates the actions of the 1,25-dihydroxyvitamin D3 hormone to effect bone mineral homeostasis. Employing mutational analysis, we characterized Arg-18/Arg-22, hVDR residues immediately N-terminal of the first DNA binding zinc finger, as vital for contact with human basal transcription factor IIB (TFIIB). Alteration of either of these basic amino acids to alanine also compromised hVDR transcriptional activity. In contrast, an artificial hVDR truncation devoid of the first 12 residues displayed both enhanced interaction with TFIIB and transactivation. Similarly, a natural polymorphic variant of hVDR, termed F/M4 (missing a FokI restriction site), which lacks only the first three amino acids (including Glu-2), interacted more efficiently with TFIIB and also possessed elevated transcriptional activity compared with the full-length (f/M1) receptor. It is concluded that the functioning of positively charged Arg-18/Arg-22 as part of an hVDR docking site for TFIIB is influenced by the composition of the adjacent polymorphic N terminus. Increased transactivation by the F/M4 neomorphic hVDR is hypothesized to result from its demonstrated enhanced association with TFIIB. This proposal is supported by the observed conversion of f/M1 hVDR activity to that of F/M4 hVDR, either by overexpression of TFIIB or neutralization of the acidic Glu-2 by replacement with alanine in f/M1 hVDR. Because the f VDR genotype has been associated with lower bone mineral density in diverse populations, one factor contributing to a genetic predisposition to osteoporosis may be the F/f polymorphism that dictates VDR isoforms with differential TFIIB interaction.

Amino Acid Sequence↗
PubMed1999

Characterization of unique DNA-binding and transcriptional-activation functions in the carboxyl-terminal extension of the zinc finger region in the human vitamin D receptor.

The vitamin D receptor (VDR) binds 1,25-dihydroxyvitamin D(3) and mediates its actions on gene transcription by heterodimerizing with retinoid X receptors (RXRs) on direct repeat (DR+3) vitamin D responsive elements (VDREs) located in target genes. The VDRE binding function of VDR has been primarily ascribed to the zinc finger region (residues 24-87). To define the minimal VDRE binding domain for human VDR (hVDR), a series of C-terminally truncated hVDR mutants (Delta134, Delta113, Delta102, Delta90, Delta84, Delta80, and Delta60) was generated and expressed in bacteria. Only the Delta134 and Delta113 mutants bound the VDRE (predominantly as monomers), suggesting that, in addition to the conserved zinc finger region of hVDR, as many as 25 amino acids in a C-terminal extension (CTE) participate in DNA binding. Site-directed mutagenesis of conserved charged residues in full-length hVDR was then performed to dissect the functional significance of the CTE (residues 88-112) in the context of the complete hVDR-RXR-VDRE interaction. Functional assays revealed that E98K/E99K, R102A/K103A/R104A, and K109A/R110A/K111A mutant hVDRs possessed dramatically reduced DNA binding and transcriptional activities, whereas distinct point mutants, such as K103A, bound to DNA normally but lacked transcriptional activity. Therefore, the boundary for the minimal DNA-binding domain in hVDR extends C-terminal of the zinc fingers to Lys-111, with clusters of highly conserved charged amino acids playing a crucial role in binding to the DR+3 element. Further, individual residues in this region (e.g., Lys-103) may lie on the opposing face of a DNA-binding alpha-helix, where they could contact transcriptional coactivators or basal transcription factors.

Amino Acid Sequence↗
PubMed1999

Vitamin D receptor displays DNA binding and transactivation as a heterodimer with the retinoid X receptor, but not with the thyroid hormone receptor.

The vitamin D receptor (VDR) is a transcription factor believed to function as a heterodimer with the retinoid X receptor (RXR). However, it was reported [Schräder et al., 1994] that, on putative vitamin D response elements (VDREs) within the rat 9k and mouse 28k calcium binding protein genes (rCaBP 9k and mCaBP 28k), VDR and thyroid hormone receptor (TR) form heterodimers that transactivate in response to both 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and triiodothyronine (T(3)). We, therefore, examined associations of these receptors on the putative rCaBP 9k and mCaBP 28k VDREs, as well as on established VDREs from the rat osteocalcin (rOC) and mouse osteopontin (mOP) genes, plus the thyroid hormone response element (TRE) from the rat myosin heavy chain (rMHC) gene. In gel mobility shift assays, we found no evidence for VDR-TR heterodimer interaction with any tested element. Further, employing these hormone response elements linked to reporter genes in transfected cells, VDR and TR mediated responses to their cognate ligands only from the rOC/mOP and rMHC elements, respectively, while the CaBP elements were unresponsive to any combination of ligand(s). Utilizing the rOC and mOP VDREs, two distinct repressive actions of TR on VDR-mediated signaling were demonstrated: a T(3)-independent action, presumably via direct TR-RXR competition for DNA binding, and a T(3)-dependent repression, likely by diversion of limiting RXR from VDR-RXR toward the formation of TR-RXR heterodimers. The relative importance of these two mechanisms differed in a response element-specific manner. These results may provide a partial explanation for the observed association between hyperthyroidism and bone demineralization/osteoporosis.

Animals↗
PubMed1999

Clinical and angiographic characteristics of exertion-related acute myocardial infarction.

CONTEXT: Vigorous physical exertion transiently increases the risk of acute myocardial infarction (MI), but little is known about the clinical characteristics of exertion-related MI. OBJECTIVE: To compare the clinical and angiographic characteristics of patients who had an exertion-related acute MI vs those who experienced an MI not related to exertion. DESIGN AND SETTING: Prospective observational cohort study of patients with an acute MI referred to a tertiary care hospital for primary angioplasty. PATIENTS: Of 1048 patients with acute MI, 640 (64 who experienced an exertion-related MI and 576 who did not) were selected for treatment with primary angioplasty and admitted between August 1995 and November 1998. MAIN OUTCOME MEASURES: Clinical characteristics of the patients, including their habitual physical activity (determined by the Framingham Physical Activity Index and the Lipid Research Clinic Physical Activity Questionnaire), angiographic findings during coronary angiography, and the relative risk (RR) of MI during exertion. RESULTS: Patients who experienced exertion-related MI were more frequently men (86% vs 68%), hyperlipidemic (62% vs 40%), and smokers (59% vs 37%), were more likely to present with ventricular fibrillation (20% vs 11%), Killip classification III or IV heart failure (44% vs 22%), single-vessel disease (50% vs 28%), and a large thrombus in the infarct artery (64% vs 35%) and were more likely to be classified as having very low or low activity (84% vs 66%). The RR of experiencing an MI during exertion was 10.1 times greater than the risk at other times (95% confidence interval [CI], 1.6-65.6), with the highest risk among patients classified as very low active (RR, 30.5; 95% CI, 4.4-209.9) and low active (RR, 20.9; 95% CI, 3.1-142.1). CONCLUSION: These results show that exertion-related MIs occur in habitually inactive people with multiple cardiac risk factors. These individuals may benefit from modest exercise training and aggressive risk-factor modification before they perform vigorous physical activity.

Cardiac Catheterization↗
PubMed1999

The silent period after magnetic brain stimulation in generalized tetanus.

The cortical silent period has not previously been studied in tetanus. Transcranial magnetic brain stimulation in a patient with generalized tetanus revealed enlarged electromyographic (EMG) responses and absence or reduction of the late phase of EMG silence following the motor evoked potential in sternomastoid and biceps brachii muscles. Following clinical recovery, the silent period returned to normal. This observation is interpreted as evidence of impaired inhibitory mechanisms at multiple levels of the nervous system, including the cortex, in generalized tetanus.

Electric Stimulation↗
PubMed1999

Pathophysiology of chorea and bradykinesia in Huntington's disease.

This article reviews the neurophysiological abnormalities described in Huntington's disease. Among the typical features of choreic movements are variable and random patterns of electromyographic (EMG) activity, including cocontraction of agonist and antagonist muscles. Studies of premotor potentials show that choreic movements are not preceded by a Bereitschaftspotential, therefore demonstrating that choreic movement is involuntary. Early cortical median-nerve somatosensory-evoked potentials have reduced amplitudes and the reduction correlates with reduced glucose consumption in the caudate nucleus. Long-latency stretch reflexes evoked in the small hand muscles are depressed. These findings may reflect failed thalamocortical relay of sensory information. In Huntington's disease, the R2 response of the blink reflex has prolonged latencies, diminished amplitudes, and greater habituation than normal. These abnormalities correlate with the severity of chorea in the face. Patients with Huntington's disease perform simple voluntary movements more slowly than normal subjects and with an abnormal triphasic EMG pattern. Bradykinesia is also present during their performance of simultaneous and sequential movements. Eye movements show abnormalities similar to those seen in arm movements. In Huntington's disease, arm movement execution is associated with reduced PET activation of cortical frontal areas. Studies using transcranial magnetic stimulation show that patients with Huntington's disease have normal corticospinal conduction but some patients have a prolonged cortical silent period. Bradykinesia results from degeneration of the basal ganglia output to the supplementary motor areas concerned with the initiation and maintenance of sequential movements. The coexisting hyperkinetic and hypokinetic movement disorders in patients with Huntington's disease probably reflect the involvement of direct and indirect pathways in the basal ganglia-thalamus-cortical motor circuit.

Basal Ganglia↗
PubMed1999

Bilateral cortical control of the human anterior digastric muscles.

Transcranial magnetic stimulation (TCMS) was used to determine the organization of cortical motor projections to the anterior digastric muscles in 12 normal human subjects. Two distinct types of potentials were evoked in anterior digastric with a figure-of-eight coil. A short-latency (3 ms) response appeared bilaterally on the surface electromyogram (EMG), but only ipsilaterally on intramuscular recordings: this was the result of direct stimulation of the ipsilateral trigeminal motor root. Motor evoked potentials (MEPs) were elicited in the anterior digastric muscles at variable onset latencies of around 10 ms by stimulation of scalp areas antero-lateral to the area for the first dorsal interosseous muscle of the hand. These were evoked bilaterally in relaxed anterior digastric muscles in six of the seven subjects. In the other subject, the responses in the relaxed muscle were exclusively ipsilateral. However, when the anterior digastric muscles were contracted, the responses were bilateral in all subjects. TCMS and spike-triggered averaging revealed that the bilateral responses were not due to the branching of axons from individual digastric motoneurones to muscles on each side. Because the digastric motor nucleus may contain separate populations of ipsi- and contralateral projecting motoneurones, it was necessary to study single motor-unit responses to TCMS to demonstrate a bilateral corticobulbar projection. The responses of 17 single motor units in the anterior digastric muscle to TCMS were recorded. All were activated by contralateral stimulation. Approximately 80% were also activated by ipsilateral TCMS, although one well-characterised motor unit was inhibited by ipsilateral TCMS. When bilateral activation was present, the ipsilateral responses were more secure than the contralateral responses, which may indicate an additional interneurone in the pathway to the contralateral motoneurone. The major conclusions from this study are that (1) the cortical representation of the anterior digastric muscle is antero-lateral to hand muscles; (2) the cortical projection to the anterior digastric muscles is bilateral; (3) the corticobulbar projection is stronger contralaterally than ipsilaterally but may involve at least one additional synapse; and (4) anterior digastric motoneurones do not branch to innervate the muscles bilaterally.

Adult↗
PubMed1999

Motor cortical control of human masticatory muscles.

The corticotrigeminal projections to masseter and anterior digastric motoneuron pools that are activated by TMS are bilateral, but not symmetrical. This conclusion is supported by whole-muscle data showing larger MEPs in the contralateral muscle with unilateral focal TMS, as well as evidence that TMS stimulation of one hemisphere may produce excitation in a masseter or digastric single motor unit while stimulation of the opposite hemisphere produced inhibition of the same motor unit. The asymmetry is particularly marked for masseter, in which the low-threshold motor units were most commonly excited with contralateral TMS and inhibited with ipsilateral TMS. Spike-triggered averaging of digastric motor unit activity revealed cross-talk in surface EMG recordings from digastric muscles, and no evidence that muscle fibres in both digastric muscles were innervated by a common motor axon. Narrow excitatory peaks in the PSTH of motor unit discharge elicited by TMS in masseter (either hemisphere) and digastric motor units (ipsilateral hemisphere) suggest a direct corticomotoneuronal projection. The contralateral projection to digastric motoneurons may include additional oligosynaptic connections, as judged by the broader peaks in the PSTH with contralateral TMS. The organisation of bilateral corticotrigeminal inputs revealed with TMS suggests that: (a) the contralateral hemisphere provides relatively more of the excitatory input delivered via the fast corticotrigeminal pathway for both masseter and digastric motoneuron pools, and (b) corticotrigeminal projections from either hemisphere are capable of contributing to the voluntary command mediating activation of masseter, and (to a lesser extent) anterior digastric muscles on one side, that is independent of the homologous muscles on the other side.

Adult↗
PubMed1999

Voluntary movement after pallidotomy in severe Parkinson's disease.

The mechanisms of improvement in parkinsonian bradykinesia after posteroventral pallidotomy were investigated in 17 patients undergoing unilateral pallidotomy for severe Parkinson's disease. Clinical ratings of 'off' period bradykinesia demonstrated a maximal improvement of 22% 3 months postoperatively. Kinematic assessments of rapid repetitive finger and sequential arm movements were performed after overnight withdrawal of antiparkinsonian medications. There was a bilateral reduction in the inter-onset latency of a two-stage sequential arm movement and a contralateral increase in speed of arm movement after pallidotomy. There was no significant improvement postoperatively in the rhythm, amplitude or speed of repetitive finger movements. The results confirm the clinical impression that pallidotomy improves bradykinesia. This was more evident for complex limb movements, which used attentional strategies and external (visual and auditory) cues, than for repetitive fingertapping movements, which were largely internally generated. Since ablation of the pallidum can only reduce inhibitory pallidal outflow, it is unlikely to restore the normal pallidal influence on thalamocortical motor circuits. Therefore, any improvement in bradykinesia after pallidotomy must be related to mechanisms other than restoration of pallidothalamocortical connectivity. Based on the above observations, we suggest that some of the changes in motor control may be explained by the greater efficacy of external cues in facilitating movement after withdrawal of the abnormal pallidal discharge.

Aged↗