Search PubMed⌕ Search

Biomedical subjects

P D Thompson

Publications and source records attributed to P D Thompson.

At least 127 records · Page 7Linked to original sources
PubMed1995

Effect of doxazosin or atenolol on exercise performance in physically active, hypertensive men.

The effects of doxazosin or atenolol on exercise capacity in 15 male distance runners (mean age +/- SD 43 +/- 10 years) were compared in a double-blind, crossover study. Subjects performed a maximal treadmill test and a timed 2-mile run before and after each drug treatment. Cardiac output was determined by acetylene rebreathing at rest and at 30%, 50%, and 75% of maximal oxygen consumption. Oxygen consumption was determined at the above-mentioned workloads and at maximal effort. Both drugs were titrated to produce similar reductions in blood pressure and the final doses of atenolol and doxazosin were 43 +/- 22 and 6 +/- 6 mg, respectively. Atenolol reduced cardiac output (p < 0.05) and heart rate (p < 0.001) at rest and at all exercise intensities compared with the prior placebo phase, whereas doxazosin increased cardiac output at rest and at 50% effort (p < 0.05). Consequently, cardiac output was higher (p < 0.01) with doxazosin than with atenolol at rest and at 30% and 50% effort. Heart rate was higher with doxazosin (p < 0.01) during all exercise workloads. Despite these changes in cardiovascular function, there were no significant differences between the effect of the 2 study drugs on maximal oxygen consumption or 2-mile run times. We conclude that atenolol decreases rest and exercise heart rate and cardiac output compared with doxazosin, but that at modest doses neither drug adversely affects exercise performance in male hypertensive runners.

Adult↗
PubMed1995

A positron emission tomography study of cerebral activation associated with essential and writing tremor.

OBJECTIVE: To compare the abnormal patterns of cerebral activation associated with essential and writing tremors. DESIGN: Positron emission tomography using oxygen 15-labeled water was utilized to determine regional cerebral blood flow. Positron emission tomography images that were taken of the brain in individual patients were coregistered with magnetic resonance images of the same brain to ascertain accurate localization of cerebral activation in single patients. Patients with essential tremor underwent scanning at rest, during involuntary postural tremor, and during passive wrist oscillation. Normal control subjects underwent scanning at rest and during voluntary and passive wrist oscillation. Patients with writing tremor underwent scanning while they were holding a pen to paper with consequent involuntary tremor and again while they were holding a pen in the same supinated arm without tremor. SETTING: Research hospital. PATIENTS OR OTHER PARTICIPANTS: Seven patients with essential tremor, six patients with writing tremor, and six matched control subjects. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Regional cerebral blood flow. RESULTS: Essential tremor was associated with abnormal bilateral cerebellar, red nuclear, and thalamic activation. Writing tremor was also associated with abnormal bilateral cerebellar activation. Voluntary wrist oscillation in control subjects caused only ipsilateral cerebellar activation. These findings were evident in single patients, when positron emission tomography images were coregistered with magnetic resonance images and on group analysis of the pooled positron emission tomography data after transformation into stereotaxic space. CONCLUSION: These results indicate that both essential and writing tremors are associated with abnormal bilateral overactivity of cerebellar connections.

Adult↗
PubMed1995

The bereitschaftspotential preceding stepping in patients with isolated gait ignition failure.

The cerebral activity preceding voluntary, self-paced ankle dorsiflexion movements while seated was compared with that before a stepping movement of the same foot while standing in four patients with isolated gait ignition failure. Results within the patients group were variable, but all exhibited some increase in the Bereitschaftspotential (BP) amplitude when stepping as compared with sitting, similar to that seen in normal subjects. This differs from previous results in patients with Parkinson's disease in which stepping was not accompanied by a normal increase in BP amplitude. This difference suggests that the mechanisms responsible for the start hesitation that is common to both Parkinson's disease and gait ignition failure may differ in the two conditions.

Aged↗
PubMed1995

The movement-related cortical potential is abnormal in patients with idiopathic torsion dystonia.

Voluntary movements, such as the self-paced finger extension task used in the present experiments, are preceded by a slowly rising negative electroencephalographic potential [the movement-related cortical potential (MRCP)]. The early NS1 component of the potential was no different in patients with primary dystonia affecting the arm (n = 6) compared with matched controls. In contrast, the peak amplitude of the MRCP was smaller in the patients, despite the fact that the movements made by the two groups were very similar; it was of equal size over both left and right hemispheres, rather than being larger on the side contralateral to the movement. These results are similar to those observed by others in patients with symptomatic dystonia secondary to lesions of the basal ganglia or their output pathways and may reflect abnormal basal ganglia input to motor areas of cortex before the onset of a self-paced movement.

Adult↗
PubMed1995

Variations in plasma volume affect total and low-density lipoprotein cholesterol concentrations during the menstrual cycle.

Serum lipids are known to vary during the menstrual cycle. To determine if changes in plasma volume contribute to this effect, we determined serum lipids, lipoproteins, and estimated changes in plasma volume in 18 premenopausal women at the start of and at 5-day intervals after menstruation. Eleven men served as a comparison group. Changes in plasma volume were estimated from changes in hemoglobin and hematocrit. Total and low-density lipoprotein (LDL) cholesterol (mean +/- SD) increased 15 +/- 14 mg/dL (9% +/- 10%) and 11 +/- 13 (11% +/- 14%) within 10 days after the start of menstruation (P < .05) and then decreased toward baseline during the rest of the cycle. High-density lipoprotein (HDL) cholesterol increased 3 mg/dL, or 5%, (P < .05) on days 10 and 15 after menstruation. Plasma volume decreased 4% +/- 9% (P < .06) 10 days after the start of menstruation, and this maximum decrease in plasma volume coincided with peak increases in total, LDL, and HDL cholesterol. Except for an 8-mg/dL increase in LDL cholesterol at day 5, lipid changes were no longer significant after adjusting for changes in plasma volume. We conclude that alterations in plasma volume account for approximately half of the increase in total and LDL cholesterol during the menstrual cycle.

Adult↗
PubMed1995

New understanding of the molecular mechanism of receptor-mediated genomic actions of the vitamin D hormone.

The nuclear vitamin D receptor (VDR) binds the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]hormone with high affinity and elicits its actions to regulate gene expression in target cells by binding to vitamin D-responsive elements (VDREs). VDREs in positively controlled genes such as osteocalcin, osteopontin, beta 3-integrin, and vitamin D-24-OHase are direct hexanucleotide repeats with a spacer of three nucleotides. The VDR associates with these VDREs with the greatest affinity as a heterodimer with one of the family of retinoid X receptors (RXRs). VDR consists of an N-terminal zinc finger domain that determines DNA binding, a "hinge" segment and a C-terminal hormone binding domain which also contains two conserved regions that engage in heterodimerization with an RXR on the VDRE. The role of the 1,25(OH)2D3 ligand in transcriptional activation by the VDR-RXR heterodimer is to alter the conformation of the hormone-binding domain of VDR to facilitate strong dimerization with RXR, which results in ligand-enhanced association with the VDRE. Thus RXR is recruited into a heterocomplex by liganded VDR. The natural ligand for the RXR coreceptor, 9-cis retinoic acid, suppresses both VDR-RXR binding to the VDRE and 1,25(OH)2D3-stimulated transcription, indicating that 9-cis retinoic acid diverts RXR away from being the silent partner of VDR to instead form RXR homodimers. Recent data reveal that after binding RXR, a subsequent target for VDR in the vitamin D signal transduction cascade is basal transcription factor IIB (TFIIB).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Progressive myoclonic ataxia associated with coeliac disease. The myoclonus is of cortical origin, but the pathology is in the cerebellum.

We report four patients with a progressive myoclonic ataxic syndrome and associated coeliac disease. The onset of the neurological syndrome followed the gastrointestinal and other manifestations of coeliac disease while on a gluten-free diet, in the absence of overt features of malabsorption or nutritional deficiency. The condition progressed despite strict adherence to diet. The neurological syndrome was dominated by action and stimulus sensitive myoclonus of cortical origin with mild ataxia and infrequent seizures. Plasmapharesis and immunosuppressive treatment were tried in two patients but were not beneficial. Post-mortem examination of the brain in one case showed selective symmetrical atrophy of the cerebellar hemispheres with Purkinje cell loss and Bergmann astrocytosis, and with preservation of the cerebral hemispheres and brainstem. Coeliac disease should be considered in the differential diagnosis of all patients presenting with a progressive myoclonic ataxic syndrome.

Adult↗
PubMed1995

Primary writing tremor.

Primary writing tremor (PWT) is considered to be a type of task-specific tremor in which tremor predominantly occurs and interferes with handwriting. We describe the clinical and neurophysiological features of 21 patients (20 male and one female) with PWT. Mean age at tremor onset was 50.1 years. A family history of PWT was obtained from seven patients. Ten patients obtained benefit from drug treatment (mainly propranalol or primidone) and seven responded to alcohol. The writing speeds of the patients (mean +/- SEM: 73.1 +/- 6.6 letters per minute) when using their preferred hand were significantly reduced (Student's t test: P < 0.001) compared with those of healthy control subjects (mean +/- SEM: 127.7 +/- 6.4). Surface polymyography performed during writing showed 4.1-7.3 Hz rhythmic activity predominantly in the intrinsic hand and forearm muscles. Alternating, extensor activation alone, skipping from alternating to extensor activation, and co-contracting EMG patterns were recorded from the flexor and extensor muscles of the forearm. There was no evidence for excessive 'overflow' of this rhythmic EMG activity, as similar activity was detected in comparable muscle groups of healthy control subjects. Accelerometry confirmed that the frequency of PWT ranged from 4.1-7.3 Hz (median 5.5 Hz) and that normal subjects wrote with a 4.0-7.7 Hz oscillation (median 4.6 Hz). Forearm reciprocal inhibition was normal in PWT (n = 13), and thus patients with PWT can be distinguished from those with writer's cramp in whom decreased presynaptic inhibition has been found. Patients were sub-classified as having either type A (n = 11) or B (n = 10) PWT depending on whether tremor appeared during writing (type A: task induced tremor) or whilst writing and adopting the hand position used in writing (type B: positionally sensitive tremor). However, the only differences between these two groups were that a co-contracting EMG pattern and tremor induced by tendon taps to the volar aspect of the wrist were present in type B but not type A cases.

Adult↗
PubMed1995

Exacerbation of postural tremor with emergence of parkinsonism after treatment with neuroleptic drugs.

Neuroleptic medication in three patients with prior isolated postural arm tremor led to a conspicuous deterioration; the postural tremor increased in amplitude, tremor appeared at rest, and other signs of mild parkinsonism developed. Withdrawal of neuroleptic drugs led to improvement in tremor and disappearance of parkinsonism. Positron emission tomography showed no reduction in uptake of [18F]dopa into nigrostriatal terminals suggesting that these patients did not have Parkinson's disease. Neuroleptic drugs can convert postural essential arm tremor into that characteristic of Parkinson's disease in patients with no evident nigrostriatal lesion.

Adult↗
PubMed1995

A highly conserved region in the hormone-binding domain of the human vitamin D receptor contains residues vital for heterodimerization with retinoid X receptor and for transcriptional activation.

Residues located between amino acids 244 and 263 in the human vitamin D receptor (hVDR) show extensive homology with other members of the steroid/thyroid/retinoid hormone receptor superfamily. The corresponding region of the glucocorticoid receptor has been shown to interact with the 90-kilodalton heat shock protein (hsp90), yet hVDR does not appear to bind to hsp90. Herein we report a study of hVDR in which the functional role of five conserved residues was tested by replacing Phe-244, Lys-246, Leu-254, Gln-259, and Leu-262 with glycines by site-directed mutagenesis. Initial screening of these mutants indicated that all were significantly impaired in their ability to activate transcription from a vitamin D-responsive reporter construct when expressed in transfected VDR-deficient COS-7 cells. Further characterization revealed two classes of mutants: the predominant class binds the 1,25-dihydroxyvitamin D3 ligand normally but is defective in its ability to form a heterodimeric complex with the retinoid X receptor (RXR) on a vitamin D responsive element (VDRE). A second unique class, represented by a single mutant at Lys-246, is normal both with respect to ligand binding and complex formation but still very impaired in transactivation ability. The distinction between these two classes was confirmed by the demonstration that a member of the first class, with a mutation at Gln-259, could be restored to near wild type transactivation ability by supplying excess RXR, while the Lys-246 mutant could not be so rescued. We therefore conclude that the primary function of this conserved domain in hVDR is the mediation of heterodimerization with RXR, leading to VDRE binding and transactivation. The possibility also exists that the Lys-246 mutant may be impaired in a step of transactivation that is distal to complex formation with RXR on the VDRE, perhaps in interactions with the transcriptional machinery itself.

Amino Acid Sequence↗
PubMed1994

Effect of tonic voluntary activity on the excitability of human motor cortex.

1. The threshold for obtaining EMG responses after transcranial magnetic stimulation of the brain is reduced by voluntary contraction of the target muscle. The present experiments tested whether some of this effect is due to increased cortical, as opposed to spinal, excitability during the contraction. 2. Magnetic stimulation was delivered with a figure-of-eight coil oriented with the junction region along the interaural line and also (in 4 of 7 subjects) with a circular coil centred at the vertex. The intensity of the conditioning stimulus was subthreshold for evoking a motor response in the relaxed wrist flexor muscles of the forearm. The presence of a small descending corticospinal volley in both the relaxed and active conditions was detected by measuring the facilitation of test H reflexes elicited in the flexor muscles of the forearm. 3. In all subjects, magnetic stimulation with either coil facilitated the H reflex at conditioning-test intervals of -1 to -3 ms (median nerve stimulus before magnetic). This was followed by a long-lasting facilitation. In three of the seven subjects stimulation with the figure-of-eight coil elicited an additional, earlier peak of facilitation at a conditioning-test interval of -3 to -5 ms. 4. In all subjects, the threshold for obtaining facilitation of the H reflex using a conditioning-test interval of -1 to -3 ms was reduced, and the amount of facilitation was larger, if subjects performed a weak tonic voluntary contraction. In contrast, with a conditioning-test interval of -3 to -5 ms voluntary contraction had no effect on the threshold. 5. It is suggested that H reflex facilitation at the conditioning-test interval of -1 to -3 ms was produced by indirect activation of corticospinal neurones by the magnetic stimulus, whereas at -3 to -5 ms, the facilitation was produced by direct activation of corticospinal axons. It is concluded that tonic voluntary contraction of a target muscle decreases the threshold for indirect activation of corticospinal neurones but not for direct stimulation of their axons.

Conditioning, Psychological↗
PubMed1994

Red nuclear and cerebellar but no olivary activation associated with essential tremor: a positron emission tomographic study.

There has been debate as to whether essential tremor has a central origin and over the possible role of the inferior olivary nucleus in its genesis. We used positron emission tomography with radioactive water (H2(15)O) to detect abnormal patterns of cerebral activity associated with this condition, at rest, without tremor, and on posture when the tremor was present. At rest, cerebellar blood flow was significantly increased bilaterally in the group with essential tremor (30-40%) but no increased olivary activity was evident. Essential tremor during arm extension was associated with further abnormal increases in bilateral cerebellar and abnormal red nuclear activation. Again, no olivary overactivity was evident. Voluntary wrist oscillation in control subjects caused only ipsilateral cerebellar activation. We conclude that essential tremor is associated with abnormal bilateral overactivity of cerebellar and red nuclear connections but found no evidence of intrinsic overactivity of the inferior olivary nucleus, as evidenced by raised blood flow.

Adult↗
PubMed1994

The syndrome of painful legs and moving toes.

The clinical presentation, symptoms, and signs in 20 new patients with the painful legs and moving toes syndrome are presented. Painful legs and moving toes may develop in the setting of spinal cord and cauda equina trauma, lumbar root lesions, injuries to bony or soft tissues of the feet, and peripheral neuropathy. In 4 of the 20 cases in the present study, no definite cause was found. Pain preceded the onset of toe movements in 18 cases, but in 2 the reverse sequence occurred. The pain had many of the characteristics of causalgia, but none of the patients exhibited the full picture of reflex sympathetic dystrophy, and peripheral trauma was the trigger in only 5 cases. Several patients reported that the occurrence of toe movements was closely related to the pain, although abolition of pain with lumbar sympathetic blocks was not necessarily associated with disappearance of the movements. Several features suggest a central origin for the movements. Symptoms may begin on one side and become bilateral; movements may be momentarily suppressed by voluntary action or exacerbated by changing posture; and electromyography reveals complex patterns of rhythmic activity with normal recruitment of motor units involving several myotomes. Three other patients with similar moving toes but no pain are also described. The occurrence of similar movements in the absence of pain raises the possibility that these cases represent examples at one end of a spectrum of disorders, with pain alone (causalgia) at the other end and the syndrome of painful legs and moving toes in between.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Unusual focal dyskinesias: the ears, the shoulders, the back, and the abdomen.

Fourteen patients with focal or segmental involuntary movements affecting the ears, back, shoulder girdle, and upper extremity, as well as the abdomen and pelvic girdle, are presented. The unusual locations and appearance of these dyskinesias distinguishes them from recognized movement disorder syndromes. It is argued that the slow, sinuous, and semirhythmic character of the movements and the variable long-duration bursts of motor unit activity responsible for them most closely fit into the spectrum of dystonia. A history of pain in the affected region and/or peripheral trauma in some cases also suggests that peripheral factors may play a role in their pathogenesis.

Abdominal Muscles↗
PubMed1994

Propriospinal myoclonus: evidence for spinal "pattern" generators in humans.

The clinical and electrophysiological characteristics of eight patients with propriospinal myoclonus are described. Myoclonus developed within days or weeks of cervical trauma in half the patients. Seven cases had axial flexion jerks, and one axial extension jerks. Myoclonic EMG activity consisted of repetitive bursts with a frequency of 1-7 Hz. The jerks in three of the cases were comprised of alternating and rhythmic bursts of EMG activity in rectus abdominis and the paraspinal muscles. From these new observations, it is proposed that cervical trauma can lead to the partial release of a spinal pattern generator. The latter is capable of recruiting muscles through long propriospinal pathways into complex rhythmic activity.

Adult↗
PubMed1994

Cortical myoclonus in Huntington's disease.

We describe three patients with Huntington's disease, from two families, in whom myoclonus was the predominant clinical feature. The diagnosis was confirmed at autopsy in two cases and by DNA analysis in all three. These patients all presented before the age of 30 years and were the offspring of affected fathers. Neurophysiological studies documented generalised and multifocal action myoclonus of cortical origin that was strikingly stimulus sensitive, without enlargement of the cortical somatosensory evoked potential. The myoclonus improved with piracetam therapy in one patient and a combination of sodium valproate and clonazepam in the other two. Cortical reflex myoclonus is a rare but disabling component of the complex movement disorder of Huntington's disease, which may lead to substantial diagnostic difficulties.

Adult↗