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Biomedical subjects

Peter Brown

Publications and source records attributed to Peter Brown.

At least 91 records · Page 5Linked to original sources
PubMed2003

The effects of an awareness-raising program for patients and primary care physicians on the early detection of gastro-oesophageal cancer.

OBJECTIVE: To test the efficacy of education by home letter, together with improved specialist/GP liaison, in promoting the detection of treatable gastro-oesophageal cancer in patients over 40. DESIGN: Prospective non-randomized trial with matched control group. PARTICIPANTS: 37,500 individuals over 40, registered with 12 general practices, were sent yearly letters for 3 consecutive years, advising them to consult a doctor with 4 specific symptoms. A matched control population of 60,500 received no intervention. MAIN OUTCOME MEASURES: Cancer cases were identified from cancer registry data, and the stage distribution and operability rates calculated from review of hospital case notes. RESULTS: Twenty of 59 cancer patients in the study group (34%) and 42 of 125 in the control group (34%) underwent resections; 24% (14/59) of study group and 18% (23/125) of control patients had "curable" disease (odds ratio [OR]= 1.51 [95%CI 0.71-3.23], X(2) = 1.164, P = 0.28). In year 1 of the study, 11 of 20 (55%) study group patients underwent resection compared to P 10 of 38 (26%) control group patients (P = 0.045, Fisher's exact test, OR = 3.4 [95% CI 1.09-0.7]). In year 1, 8 of 20 study patients (40%) had "curable" disease compared to 10.5% (4/38) control patients (P = 0.0128 Fisher's exact test, OR = 5.67 [95% CI 1.44 - 22.3]). There was no difference in survival between the groups overall or on comparing each year of study. CONCLUSION: This intervention caused a transient marked improvement in resection rate and curability, but the longer term impact on stage and resection rate was nonsignificant, and survival was not affected. Improving the detection of curable upper GI cancer is likely to require more complex and intensive interventions.

Adult↗
PubMed2002

Persistent effects of high frequency repetitive TMS on the coupling between motor areas in the human.

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a treatment for various movement and psychiatric disorders. How rTMS may have persistent effects on cortical function remains unclear. We hypothesised that it may act by modulating cortico-cortical connectivity. To this end we assessed cortico-cortical coherence before and after high frequency rTMS of the motor cortex. Sixteen healthy subjects received a single train (5 Hz, active motor threshold, 50 stimuli) of rTMS to the left motor hand area. Spectral power and coherence estimates were calculated between different EEG signals at rest and while muscles of the distal upper limb were tonically contracted. Repetitive TMS over the left motor hand area caused a significant decrease in the intrahemispheric EEG-EEG coherence between motor and premotor cortex in the 10.7-13.6 Hz (upper alpha band) lasting a few minutes after stimulation. There was no significant change in interhemispheric EEG-EEG coherence between motor areas. Thus, high frequency rTMS of the motor cortex decreases ipsilateral cortico-cortical intrahemispheric in the upper alpha band.

Adult↗
PubMed2002

The functional role of interhemispheric synchronization in the control of bimanual timing tasks.

The aim of the present study was to investigate whether synchronized activity between the right and left primary sensorimotor cortices has a functional role in the organization of bimanual in-phase and anti-phase movement patterns, performed at different cycling frequencies. To this end we evaluated the cortical dynamics by means of task-related EEG. Both behavioral performance and coupling between the primary sensorimotor cortices in the beta frequency band were reduced with increasing movement speed, and this effect was far more powerful in the anti-phase than in-phase mode. Thus, a progressive degradation of interhemispheric connectivity with cycling rate was associated with a deteriorating behavioral output. Overall, these results support a significant role for interhemispheric synchronization in the control of bimanual movements.

Adult↗
PubMed2002

Pallidal activity recorded in patients with implanted electrodes predictively correlates with eventual performance in a timing task.

Here we seek to establish whether there are activities in the human pallidum that may predict a specific aspect of performance, timing. When recording from two patients with Parkinson's disease and primary generalised dystonia following functional neurosurgery we found that the amplitude of oscillatory pallidal activity occurring prior to the completion of a bimanual timing task was strongly correlated with eventual task duration. The frequency of this oscillatory activity was around 25 Hz. We conclude that the human pallidum may be involved in the prediction of movement timings and that such internal estimates may be reflected in amplitude modulation of oscillatory activity around 25 Hz.

Beta Rhythm↗
PubMed2002

Repetitive transcranial magnetic stimulation of the supplementary motor area (SMA) degrades bimanual movement control in humans.

Moving the upper limbs at a common tempo according to an in-phase or anti-phase mode represents elementary coordination dynamics. Previously, the role of the supplementary motor area (SMA) has been emphasized for successful production of these patterns. The objective of this study was to investigate whether repetitive transcranial magnetic stimulation (rTMS) of the SMA at 5 Hz can interfere with these isofrequency configurations in the post-stimulation stage. Results showed a deterioration of temporal control as a function of coordinative complexity. This effect was associated with a decrease in the functional coupling between the primary motor cortices, as measured by electroencephalographic coherence. These data suggest that rTMS of the SMA can modify interhemispheric communication and accordingly modulate interlimb behavior.

Adult↗
PubMed2002

Arvanil-induced inhibition of spasticity and persistent pain: evidence for therapeutic sites of action different from the vanilloid VR1 receptor and cannabinoid CB(1)/CB(2) receptors.

Activation of cannabinoid receptors causes inhibition of spasticity, in a mouse model of multiple sclerosis, and of persistent pain, in the rat formalin test. The endocannabinoid anandamide inhibits spasticity and persistent pain. It not only binds to cannabinoid receptors but is also a full agonist at vanilloid receptors of type 1 (VR1). We found here that vanilloid VR1 receptor agonists (capsaicin and N-N'-(3-methoxy-4-aminoethoxy-benzyl)-(4-tert-butyl-benzyl)-urea [SDZ-249-665]) exhibit a small, albeit significant, inhibition of spasticity that can be attenuated by the vanilloid VR1 receptor antagonist, capsazepine. Arvanil, a structural "hybrid" between capsaicin and anandamide, was a potent inhibitor of spasticity at doses (e.g. 0.01 mg/kg i.v.) where capsaicin and cannabinoid CB(1) receptor agonists were ineffective. The anti-spastic effect of arvanil was unchanged in cannabinoid CB(1) receptor gene-deficient mice or in wildtype mice in the presence of both cannabinoid and vanilloid receptor antagonists. Likewise, arvanil (0.1-0.25 mg/kg) exhibited a potent analgesic effect in the formalin test, which was not reversed by cannabinoid and vanilloid receptor antagonists. These findings suggest that activation by arvanil of sites of action different from cannabinoid CB(1)/CB(2) receptors and vanilloid VR1 receptors leads to anti-spastic/analgesic effects that might be exploited therapeutically.

Animals↗
PubMed2002

Effect of treatment with intravenous immunoglobulin on quality of life in patients with stiff-person syndrome.

The therapeutic effects of intravenous immunoglobulin (IVIG) on the stiff-person syndrome (SPS) have been described exclusively in case reports or open-label studies in terms of clinical outcomes. We investigate whether IVIG improves quality of life (QoL) in the SPS. Six patients with the classic form of SPS completed a generic QoL instrument, the SF-36, and a Visual Analogue Scale (VAS) before treatment as well as 2 weeks after completion of a course of IVIG. There was significant improvement in the SF-36 subscores for pain, social functioning, general mental health, and energy-vitality with treatment. The VAS also improved significantly. We conclude that treatment with IVIG improves QoL in the SPS.

Aged↗
PubMed2002

Bilaterally coherent tremor resembling enhanced physiological tremor: report of three cases.

The contribution of the central nervous system to tremor pathogenesis is unclear. Poor side-to-side coherence in physiological, essential, and parkinsonian tremors suggests distinct bilateral generators. By contrast, significant bilateral coherence demonstrated in orthostatic tremor and in enhanced physiological tremor (EPT) in patients with persistent mirror movements favours single or closely linked bilateral oscillators. We describe three patients (aged 21-37 years) who developed unusual bilateral postural and kinetic tremors at 6-13 Hz resembling EPT. The tremor involved all limbs, and in two cases the face or jaw, in the absence of other significant neurological features. Significant side-to-side coherence was demonstrated in each case using cross-correlation of electromyographic recordings from homologous muscle pairs. We postulate that these unusual tremors originate from a single brainstem source or from bilateral oscillators closely linked at or below this level.

Adult↗
PubMed2002

Descending control of muscles in patients with cervical dystonia.

It was reported recently that specific features in the frequency analysis of electromyographic (EMG) activity in the sternocleidomastoid (SCM) and splenius (SPL) muscles were able to distinguish between rotational idiopathic cervical dystonia (CD) and voluntary torticollis in individual subjects. Those with CD showed an abnormal drive to muscles at 5 to 7 Hz and an absence of the normal 10 to 12 Hz peak in the autospectrum of SPL. We sought to determine whether the same abnormalities in the frequency domain are found in complex CD, in which the head is displaced in more than two planes. EMG activity was recorded in the SCM, SPL, trapezius, and levator scapulae muscles bilaterally in 10 patients with complex CD. Frequency analysis of EMG was compared with conventional clinical and polymyographic assessment. The autospectrum of SPL during free dystonic contraction showed an absence of a significant peak at 10 to 12 Hz in 8 of the 10 patients. The presence of a 5 to 7 Hz frequency drive showed a significant association with muscle pairs determined as dystonic by means of polymyography (P < 0.005). The neck posture predicted blindly, based on the low-frequency drive, correlated significantly with the clinical assessment of posture (P < 0.01). Conventional assessment and the results of frequency analysis correlated, suggesting that a low-frequency drive to neck muscle may be a general feature of simple rotational and more complex cervical dystonia. The pattern of coherence between the EMG in different neck muscles may provide a means of identifying leading dystonic muscles, especially in patients with complex cervical dystonia.

Adult↗
PubMed2002

Corticobasal degeneration syndrome with basal ganglia calcification: Fahr's disease as a corticobasal look-alike?

A 57-year-old man with a 5-year history of progressive left-sided rigidity and apraxia had extensive bilateral calcification of basal ganglia, centrum semiovale, dentate nuclei, and cerebellar white matter on brain imaging. The case is an example of radiological Fahr's disease accompanying a clinical syndrome of corticobasal degeneration. Possible pathogenetic and nosological implications of this association are discussed.

Basal Ganglia Diseases↗
PubMed2002

Major and minor form of hereditary hyperekplexia.

Hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses. Within the disorder two clinical forms can be distinguished. The major form is characterized by continuous generalized stiffness in the first year of life and an exaggerated startle reflex, accompanied by temporary generalized stiffness and falls, whereas in the minor form only excessive startle and hypnic jerks have been described. Mutations in the gene encoding the alpha-1 subunit of the glycine receptor (GLRA1) are responsible for the major form of hyperekplexia but no mutation was detected in patients with the minor form in the large Dutch pedigree originally described by Suhren and colleagues. Here we describe the genetic analysis of the GLRA1 gene of two English families in which both forms of hyperekplexia were present. Mutation analysis revealed no genetic defect in the GLRA1 gene in patients carrying either the minor or major forms. This is further evidence that the minor form of hyperekplexia is seldom due to a genetic defect in the GLRA1 gene.

Adolescent↗
PubMed2002

EMG-EMG coherence in writer's cramp.

We investigated the extent to which oscillatory drives to muscle, believed to arise mainly from the motor cortex, are exaggerated and/or fail to react normally to peripheral stimulation in writer's cramp. We used the coherence between active forearm flexor and intrinsic hand muscles as our index of such drives before and after digital nerve stimulation of the dominant hand. The results in 8 patients with writer's cramp were compared with those in eight age- and sex-matched healthy subjects. We found no significant difference in either the strength of intermuscular coherence or its modulation by cutaneous stimulation between patients and healthy subjects during voluntary flexion of the wrist and extension-abduction of the fingers. Therefore, we were unable to provide evidence for a pervasive disturbance of oscillatory cortical motor outflow in writer's cramp.

Adult↗
PubMed2002

Quality of life in stiff-person syndrome.

Stiff person syndrome (SPS) is a rare, chronic disorder characterized by painful spasm and stiffness. We investigated the quality of life (QoL) in SPS patients, and identified factors associated with impairment in patients' QoL. Twenty-four SPS patients (10 men, 14 women; mean age +/- S.D., 52.6 +/- 9.5 years) completed the medical outcomes study Short Form health survey (SF-36), the Beck Depression Inventory (BDI), and a questionnaire asking for sociodemographic and clinical details. Extent of the disease was assessed using a distribution of stiffness score. SPS patients showed markedly reduced mean scores for all dimensions of the SF-36 when compared to norms from the general population of the United Kingdom. QoL scores showed a strong correlation with the extent of the disease. Depression was a common finding; 14 of 24 patients had depressive symptoms as evidenced by the BDI. There was a significant and strong correlation between the BDI score and several SF-36 subscores. This is the first study to address QoL in patients with SPS. We have shown that SPS has a significant impact on patients' reported QoL. The association between depression and QoL highlights the importance of recognizing and treating depression in SPS.

Chronic Disease↗
PubMed2002

In vivo GABA editing using a novel doubly selective multiple quantum filter.

A novel multiple quantum filtering method is proposed that uses a doubly selective pulse termed Delays Alternating with Nutations for Tailored Excitation (DANTE) for multiple quantum preparation. This method selectively prepares GABA-3 and GABA-4 into a multiple quantum state and suppresses all other resonances at 3.0 ppm in each single scan. Phantom tests demonstrated excellent GABA signal retention and complete suppression of overlapping metabolites. It is shown using numerical simulations that overlapping macromolecules are suppressed because the frequency of the first upfield 2pi rotation of the doubly selective DANTE pulse coincides with that of the macromolecules at 1.72 ppm. Excellent suppression of overlapping macromolecules was demonstrated in vivo. Using this method the concentration of GABA in the occipital lobe of healthy volunteers was measured to be 1.21 +/- 0.28 micromol/mL (mean +/-SD, N = 9).

Adult↗
PubMed2002

Oscillatory local field potentials recorded from the subthalamic nucleus of the alert rat.

Hitherto, high-frequency local field potential oscillations in the upper gamma frequency band (40-80 Hz) have been recorded only from the region of subthalamic nucleus (STN) in parkinsonian patients treated with levodopa. Here we show that local field potentials recorded from the STN in the healthy alert rat also have a spectral peak in the upper gamma band (mean 53 Hz, range 46-70 Hz). The power of this high-frequency oscillatory activity was increased by 30 +/- 4% (+/-SEM) during motor activity compared to periods of alert immobility. It was also increased by 86 +/- 36% by systemic injection of the D2 dopamine receptor agonist quinpirole. The similarities between the high-frequency activities in the STN of the healthy rat and in the levodopa-treated parkinsonian human argue that this oscillatory activity may be physiological in nature and not a consequence of the parkinsonian state.

Animals↗
PubMed2002

The effects of subthreshold 1 Hz repetitive TMS on cortico-cortical and interhemispheric coherence.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) shows promise as a treatment for various movement and psychiatric disorders. Just how rTMS may have persistent effects on cortical function remains unclear. We hypothesised that it may act by modulating cortico-cortical and interhemispheric connectivity. To this end we assessed cortico-cortical and interhemispheric coherence before and after low frequency, subthreshold rTMS of the left motor cortex. METHODS: Fifteen healthy subjects received one train (1Hz, 90% of active motor threshold, 1500 stimuli) of rTMS to the left motor hand area. Spectral power and coherence estimates were calculated between different electroencephalogram (EEG) signals at rest and while muscles of the distal upper limb were tonically contracted. RESULTS: rTMS over the left motor hand area caused a significant increase in ipsilateral EEG-EEG coherence and in the interhemispheric coherence between motor areas in the alpha band. The effects of rTMS lasted up to 25 min post-stimulation. There was no significant change in EEG-EEG coherence over the hemisphere contralateral to stimulation. CONCLUSIONS: Low frequency, subthreshold rTMS of the motor cortex increases ipsilateral cortico-cortical and interhemispheric coherence in the alpha band. This may, in part, mediate the inhibitory effects of low frequency rTMS.

Adult↗