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Biomedical subjects

P D Thompson

Publications and source records attributed to P D Thompson.

At least 19 recordsLinked to original sources

"Resetting" of postural tremors at the wrist with mechanical stretches in Parkinson's disease, essential tremor, and normal subjects mimicking tremor.

The response of postural wrist tremors to brief mechanical displacements was compared in two groups of patients, one with classical hereditary essential tremor (n = 18) and another with typical Parkinson's disease (n = 13). These groups were compared with an additional group of normal subjects mimicking wrist tremor (n = 9). The degree to which brief mechanical displacements of the wrist produced by torque pulses of three different sizes could modulate the timing of rhythmic electromyographic bursts in the forearm flexor muscles was quantified by deriving a resetting index, which could range between 0 (no phase resetting) and 1 (complete phase resetting). In all three groups of subjects studied, the resetting index varied significantly with the size of the mechanical perturbation and, in an inverse fashion, with the ongoing tremor amplitude. When due allowance for these factors was made, the difference in mean resetting indexes between the three groups of patients and subjects was reduced to the extent that no definitive statement could be made as to whether brief mechanical perturbations had more effect on essential tremor than parkinsonian tremor. The method is therefore unlikely to be useful in differentiating the common causes of postural wrist tremors.

Adult

Voluntary stimulus-sensitive jerks and jumps mimicking myoclonus or pathological startle syndromes.

Five patients who presented with stimulus-induced jerking as part of an apparent myoclonic or pathological startle syndrome are reported. Neurophysiological observations in these patients suggested the jerks were voluntary in origin. These included (a) variable latencies to the onset of stimulus induced jerks, (b) latencies were greater than that seen in reflex myoclonus of cortical or brainstem origin, and were (c) longer than the fastest voluntary reaction times of normal subjects, (d) variable patterns of muscle recruitment within each jerk and, (e) significant habituation with repeated stimulation. It is argued that these features are consistent with a voluntary origin for the jerks and enable them to be distinguished from the stereotyped electrophysiological characteristics of myoclonus of cortical and brainstem origin. Electrophysiological recordings may help identify patients with this form of psychogenic movement disorder.

Adult

Primary orthostatic tremor: further observations in six cases.

The clinical and physiological features of six new patients with primary orthostatic tremor are described. We suggest that use of the term primary orthostatic tremor be confined to the clinical syndrome in which unsteadiness when standing is the predominant complaint and accompanied by characteristic electrophysiological findings of a rapid (frequency around 16 Hz), regular leg tremor which is not influenced by peripheral feedback, is synchronous between homologous leg muscles, and in certain postures of the upper limbs, between muscles of the arm and leg. The fast frequency of muscle activity in primary orthostatic tremor of the legs causes unsteadiness when standing (presumably due to partially fused muscle contraction) but only a fine ripple of muscle activity is visible. In contrast, the slower frequency of other leg tremors, for example essential tremor, results in obvious leg movement which is evident in many leg postures, is variable over time and can be reset by a peripheral nerve stimulus. Essential tremor and orthostatic tremor do not respond to the same therapies, suggesting differences in the pharmacological profiles of the two conditions. Accordingly, there are clinical, physiological and pharmacological differences between primary orthostatic and essential tremor. Whether these factors are sufficient to regard these tremors as separate conditions is discussed.

Adult

Abnormal REM sleep in the irritable bowel syndrome.

Motor abnormalities of the small bowel that occur only during the waking state have been reported in the irritable bowel syndrome (IBS), suggesting that central nervous system arousal is a necessary condition for expression of the disorder and that it may reflect inappropriate brain-gut interaction. This possible relationship was explored further by synchronous polysomnography and recording of upper small bowel motility in six healthy subjects and six patients with IBS. During sleep, there was no difference in the patterns of intestinal motility between the two groups. There was no difference between the rapid eye movement (REM) latency or number of REM episodes, but the proportion of REM sleep was markedly increased (36.5% +/- 5.7% vs. 18.2% +/- 5.7%; P less than 0.01) in the IBS group, although the duration of sleep was similar (468 +/- 13 minutes in IBS vs. 444 +/- 10 minutes in controls; P greater than 0.1). Sleep apnea was detected in three of six patients with IBS but was not seen in controls. The data are consistent with the model of IBS as a disorder of brain-gut interaction.

Adult

High-density apolipoprotein A-I and A-II kinetics in relation to regional adiposity.

High-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations decrease with increasing central adiposity. The present study investigated possible mechanisms for these effects by examining the relationship between body mass index, regional adiposity, and HDL apo A-I and A-II metabolism. Fifteen sedentary men and 10 male endurance athletes aged 22 to 44 served as subjects. HDL apo A-I and A-II metabolism was examined using 125I-labeled autologous HDL. Chest and thigh skinfold thickness and the ratio of chest to thigh skinfold thickness were used as indices of regional adiposity. The relationship of adiposity to HDL metabolism was examined using correlational and multiple regression analysis. In both subject groups, the fractional catabolic rate of apo A-I and A-II increased with increasing chest skinfold thickness and chest to thigh skinfold ratio (.43 < r2 < .66). This effect was partially independent of triglyceride or HDL cholesterol concentrations. Apo A-I and A-II fractional catabolic rates increased with increasing body mass index only in the sedentary men. Concentrations and synthetic rates (mg.d-1.kg-1) of apo A-I and A-II were not consistently related to body mass index or regional adiposity. Peripheral adiposity assessed by thigh skinfold thickness was not correlated with any parameter of apo metabolism. We conclude that HDL apo A-I and A-II catabolism increases with increasing central adiposity.

Adipose Tissue

Left ventricular function is not impaired in weight-lifters who use anabolic steroids.

Recent reports suggest that anabolic steroid use might deleteriously affect left ventricular function. To examine this possibility, the present study measured left ventricular size and function with use of Doppler echocardiographic techniques in 23 weight lifters: 12 who were currently using anabolic steroids and 11 who reported that they had never used these drugs. Drug users had administered anabolic steroids to themselves for at least three cycles over the past year. All studies were interpreted by blind review and group assignment was confirmed by urine testing. Average age, years of exercise training and body weight, as well as heart rate and blood pressure at rest were similar in both groups. Cardiac dimensions (mean +/- SD) including left ventricular diastolic cavity diameter (57 +/- 3 vs. 56 +/- 5 mm), septal thickness (10 +/- 2 vs. 9 +/- 1 mm), posterior wall thickness (8 +/- 1 vs. 8 +/- 1 mm) and myocardial mass (149 +/- 27 vs. 135 +/- 21 g) did not differ between the anabolic steroid users and nonusers, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The auditory startle response in the Steele-Richardson-Olszewski syndrome and Parkinson's disease.

The startle response to an unexpected auditory stimulus was studied in eight patients with a clinical diagnosis of the Steele-Richardson-Olszewski syndrome (SRO), 11 patients with idiopathic Parkinson's disease (PD) and 12 normal subjects. The patients with PD were studied 'on' at the time of maximal effect of their treatment; five of these patients were also studied in their 'off' state without treatment. The auditory startle response was absent in three patients with SRO: in the remaining five the latency to onset of earliest electromyography activity (EMG) of the auditory startle response was delayed and few muscles (orbicularis oculi, sternocleidomastoid and rectus abdominis) were recruited in the response. In PD the auditory startle response was similar to that recorded in normal subjects, both in terms of the pattern of muscles recruited and the amplitude of the EMG responses, but the latency of responses in orbicularis oculi and sternocleidomastoid muscles were significantly delayed. This result was not influenced by treatment with L-dopa. In patients with SRO the finding of an abnormal startle response is consistent with loss of neurons in the lower pontine reticular formation. This region is intimately involved in the startle response in animal studies. In patients with PD the late auditory startle response might be related to withdrawal of facilitatory input to brainstem centres and reticulospinal pathways from basal ganglia. The similarity of the responses in patients when 'on' and 'off' suggests these pathways are not under potent dopaminergic control.

Adult

Effect of digital nerve stimuli on responses to electrical or magnetic stimulation of the human brain.

1. Reflexes were elicited in the first dorsal interosseous muscle of seven normal subjects by electrical stimulation of the digital nerves of the index finger at 3 times perceptual threshold while subjects maintained a constant voluntary contraction of the muscle. The average response in the surface-rectified electromyogram (EMG) consisted of an early inhibitory (I1) component followed by a later excitation (E2). 2. Low intensity anodal electrical or magnetic scalp stimuli were given over the motor cortex in order to elicit muscle responses within the period of the I1 and E2 reflex components. 3. Compared with control responses elicited in the absence of digital nerve stimulation, responses to electrical cortex stimulation were suppressed in the I1 period and facilitated during the E2 period of the reflex. In contrast, responses evoked by magnetic stimulation were suppressed during I1 and also for the first 10 ms or so of the E2 response. Magnetically evoked responses were facilitated during the later part of the E2 reflex. 4. Similar effects were seen when the probability of firing of single motor units was studied. 5. In three subjects, small taps were given to the abducted index finger in order to stretch the first dorsal interosseous muscle and evoke reflexes which were of comparable size to the E2 reflex evoked by digital nerve stimulation. In contrast to the experiments in which digital nerve stimuli were given, responses evoked by magnetic stimulation over motor cortex were facilitated at all times during the course of the reflex evoked when the muscle was stretched. 6. We conclude that single electrical stimuli applied to the digital nerves can reduce for a short period the excitability of motor cortex to magnetic stimulation. This occurs at a time when the same stimulus is evoking an excitatory (E2) reflex in the average surface-rectified EMG.

Adult

Propriospinal myoclonus in multiple sclerosis.

The clinical and electrophysiological features of segmental myoclonus affecting the right arm and upper trunk are described in a patient with multiple sclerosis. Electrophysiological studies suggested that the myoclonus was propagated from a generator site in the cervical cord, where lesions were found using MRI. The spread of electromyographic activity in each myoclonic jerk was slow and variable. These findings are characteristic of propriospinal myoclonus, which has not been associated with multiple sclerosis previously.

Adult

"Isolated" postinfectious myoclonus.

Two cases are reported who developed myoclonus as the only manifestation of a post-infectious syndrome without evidence of encephalitis or the opsoclonus-myoclonus syndrome. Case 1 had generalised myoclonus following an influenza-like illness, while case 2 had right upper limb segmental myoclonus following uncomplicated chicken pox. Neither had any localising neurological signs or abnormality on investigation. Both recovered completely within six months of the onset. Similar cases are reviewed from the literature and it is suggested that such cases be called "isolated" post-infectious myoclonus.

Adolescent

Isolated tremor and disruption of the nigrostriatal dopaminergic system: an 18F-dopa PET study.

We measured striatal 18F-dopa influx constants (Ki) for 20 patients with isolated, predominantly postural, tremor (eight familial, 12 sporadic) and 11 with predominantly rest tremor. Results were compared with 30 controls and 16 Parkinson's disease (PD) patients. The eight familial essential tremor (ET) patients had normal striatal 18F-dopa uptake. Two of the 12 sporadic postural tremor patients had subnormal putamen 18F-dopa Ki, one (who later became akinetic) falling in the PD range. The mean putamen 18F-dopa uptake of the 11 rest tremor patients was reduced to PD levels (51% of normal). Our findings argue against an association between ET and PD, but support the existence of a "benign" tremulous variant of PD. The presence of low-amplitude rest tremor, cogwheel rigidity, reduced arm swing, and short tremor duration was not a useful predictor of nigral dysfunction in patients with postural tremor. In contrast, patients with predominantly rest tremor, particularly with onset in the leg, consistently showed reduced putamen 18F-dopa uptake.

Adult

Botulinum toxin treatment of spasmodic torticollis.

We reviewed the efficacy and adverse effects of repeated botulinum toxin injections into hyperactive neck muscles of 107 successive patients with spasmodic torticollis. They received 510 injection treatments over a median period of 15 months (range 3-42 months). One patient failed to benefit at all, but 101 (95%) patients reported considerable (moderate or excellent) benefit from at least one treatment. On a global subjective response rating, 93% of 429 treatments resulted in some improvement and 76% in moderate or excellent improvement. Pain reduction followed 89% of 190 treatments with moderate or excellent reduction after 66%. Median duration of benefit was 9 weeks. All torticollis types responded equally well and injections into two (or more) involved neck muscles were more effective than injection into a single muscle. The most frequent adverse effect was dysphagia, occurring after 44% of all treatments, but this was severe after only 2%. Antibodies to botulinum toxin were detected in the serum of three out of the five patients in whom loss of treatment efficacy occurred. We conclude that botulinum toxin treatment is the most effective available therapy for spasmodic torticollis and practical advice is provided for anyone wishing to set up the technique.

Adult

The preparticipation sports examination. Cardiovascular considerations for screening.

Physicians performing cardiovascular screening examinations in young and adult athletes should be aware of the rarity of exercise complications and the difficulty in separating cardiac adaptations to training from pathologic conditions. Coronary artery disease is the predominant cause of cardiac events during exercise in adults, whereas congenital abnormalities are the primary cause of exercise deaths in children. The preparticipation cardiac examination should include blood pressure measurements, visual inspection for the Marfan habitus, and auscultation designed to detect ventricular outflow obstruction. Other cardiovascular testing should be used when symptoms or findings warrant further evaluation.

Age Factors

The blood pressure response to exercise in anabolic steroid users.

We measured blood pressure at rest and during exercise in nine weight lifters using anabolic steroids, 10 weight lifters not using these drugs, and 10 sedentary controls. BP was measured using standard sphygmomanometry and an appropriately sized cuff. Maximal treadmill tests and leg press exercise were conducted in random order on separate days. Systolic blood pressure in the anabolic steroid users was higher at rest and during both forms of exercise. Diastolic blood pressure during exercise was also higher in the anabolic steroid users than in the other two groups. The maximal systolic and diastolic blood pressure change from rest to exercise was not different among the groups, suggesting that the higher exercise pressure in the drug users was primarily due to higher resting values. Body weight and biceps circumference were greatest in the anabolic steroid users. Adjusting rest and exercise blood pressure for body weight or biceps size eliminated statistically significant differences between groups, but had little impact on the absolute group differences. We conclude that the higher rest and exercise blood pressure values noted in anabolic steroid users may be related to their larger body mass or may be an artifact of the larger arm circumference in these subjects. Other factors may also be operative, however, because blood pressure remained nonsignificantly higher even after body weight and biceps size were adjusted for statistically.

Adult

Conversion of arginine to lysine at position 70 of human dihydrofolate reductase: generation of a methotrexate-insensitive mutant enzyme.

Arginine-70 of human dihydrofolate reductase (hDHFR) is a highly conserved residue which X-ray crystallographic data have shown to interact with the alpha-carboxylate of the terminal L-glutamate moiety of either folic acid or methotrexate (MTX). The rationale for this study was to introduce a conservative amino acid residue change at position 70 (Arg----Lys) which might function as a titratable group and, thus, reveal possible quantitative changes in ligand binding and kinetic parameters as a function of pH. Such a mutant enzyme (R70K) has been constructed and expressed by using site-directed mutagenesis techniques. This substitution has a dramatic effect on the binding of MTX, which displays a 22,600-fold increase in the dissociation constant (KD) at pH 7.5 compared to that of the reported wild-type enzyme value. At this pH, the KD value for dihydrofolate (FAH2) for the R70K enzyme shows only a 7-fold increase over that for the wild-type hDHFR. The pH profiles of the Michaelis and dissociation constants for FAH2 and KD values for MTX for the mutant enzyme all show a 7-8-fold increase from pH 7.5 to 8.5 as compared to its wild-type counterpart. The binding of NADPH or the nonclassical inhibitor trimetrexate (TMQ) to either the wild-type or the mutant enzyme does not show such pH-dependent characteristics. Thus, since FAH2 and MTX interact with the guanidinium side chain of arginine-70 in the wild-type hDHFR, the replacement of this residue with a lysine in the R70K mutant appears to have resulted in the introduction of a titratable group with a perturbed pKa value of ca. 8.3.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine