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Biomedical subjects

S J Graham

Publications and source records attributed to S J Graham.

At least 19 recordsLinked to original sources
PubMed2006

Magnetoencephalographic study of vibrotactile evoked transient and steady-state responses in human somatosensory cortex.

Somatosensory responses to vibrotactile stimulation applied to the index fingertip were recorded with whole-head MEG in eleven healthy young adult participants. Stimulus trains were produced by a pneumatically driven membrane oscillating at 22 Hz for a trial duration of 1 s, separated by interstimulus intervals (ISIs) of 0.5, 1.0, 3.0, and 7.0 s. Data analysis was performed in two frequency bands. Transient onset responses in the lower frequency band (<20 Hz) contained a clearly expressed P50 component. The higher frequency band (18-30 Hz) revealed a gamma-band response (GBR) within the first 200 ms followed by rhythmic activity at the stimulus frequency that continued throughout the stimulus duration, known as the steady-state response (SSR). Dipoles associated with the transient responses and SSRs were localized in two distinct regions within the primary somatosensory cortex (SI), with transient responses located on average 3 mm more medial and inferior than the SSRs. The transient and GBR peak amplitudes increased with ISI, whereas the SSR amplitude showed no ISI dependence. These results may reflect functionally and spatially distinct neural populations. Further investigations are required to assess the implications of these findings for probing the somatosensory system using other functional neuroimaging methods such as fMRI.

Adult↗
PubMed2005

Assessing linear time-invariance in human primary somatosensory cortex with BOLD fMRI using vibrotactile stimuli.

The assumption of linear time-invariance (LTI) in the human primary somatosensory cortex (SI) is assessed for fMRI signals generated by variable-duration vibrotactile stimuli. Predictions based on time-shifted summation (TSS) of responses to 2 s stimuli overestimate observed BOLD signal amplitudes in response to longer-duration stimuli, in agreement with previous findings in other primary sensory cortices. To interpret these results, we undertook an alternative approach for LTI assessment by characterizing BOLD signals using two biophysical models. The first model assumes that the input stimulus envelope is proportional to neural activity. The second assumes that neural activity exhibits both transient and steady-state components, consistent with extensive electrophysiological data, and fits the experimental data better. Although nonlinearity remains evident for short stimulus durations, the latter model shows that the TSS procedure to assess LTI overestimates the BOLD signal because the temporal characteristics of neural activity have not been considered adequately. Further research to investigate the BOLD response to time-varying neural activity is required.

Adaptation, Physiological↗
PubMed2005

Effects of lorazepam on fear-potentiated startle responses in man.

Sudden intense sensory stimuli elicit a cascade of involuntary responses, including a short-latency skeletal muscular response ('eyeblink startle response') and longer-latency autonomic responses. These responses are enhanced when subjects anticipate an aversive event compared to periods when subjects are resting ('fear potentiation'). It has been reported previously that the anxiolytic diazepam can suppress fear-potentiation of the eyeblink startle response in human volunteers. The present experiment aimed to confirm and extend these observations by examining the effect of another benzodiazepine, lorazepam, on the eyeblink and skin conductance components of the acoustic startle, and on fear-potentiation of these responses. Eighteen male volunteers participated in three weekly sessions in which they received oral treatment with placebo, lorazepam (1 mg) and lorazepam (2 mg), according to a balanced three-period, crossover, double-blind design. Two hours after ingestion of the treatments, electromyographic responses of the orbicularis oculi muscle and skin conductance responses were evoked by sound pulses during alternating periods in which the threat of an electric shock (electrodes attached to the subject's wrist) was present (THREAT) and absent (SAFE). The THREAT condition was associated with significant increase in the amplitude of the electromyographic (EMG) and skin conductance responses; there were also increases in baseline skin conductance, the number and amplitude of 'spontaneous' skin conductance fluctuations and self-rated anxiety. Lorazepam attenuated the effect of THREAT on self-rated anxiety and on the amplitude of the EMG response, but had no significant effect on fear-potentiation of the skin conductance responses. These results extend previous findings of the effect of diazepam on the fear-potentiated eyeblink startle response to lorazepam, and suggest that fear-potentiation of the later autonomic component of the startle response may be less sensitive to benzodiazepines than the fear-potentiated eyeblink response and self-rated anxiety.

Acoustic Stimulation↗
PubMed2004

The effect of ureteric stents on urine flow: reflux.

If the ureter becomes blocked, the resultant increased pressure may be relieved by inserting a double-J stent (a polymer tube, usually punctuated with holes). A major clinical problem associated with stent use is reflux (retrograde flow of urine from the bladder to the kidney), which may result in infections, scarring, and even renal failure. We develop a mathematical model, treating the ureter as an elastic tube and the stent as a permeable rigid tube within it. We investigate how the number of holes in the stent wall affects the total amount of reflux that occurs when bladder pressure rises, by considering the limits of a highly-permeable stent, and an impermeable stent. We find that, in the scenarios we consider, the highly-permeable stent gives rise to less total reflux than the impermeable one.

Humans↗
PubMed2004

Effects of quetiapine and haloperidol on prepulse inhibition of the acoustic startle (eyeblink) response and the N1/P2 auditory evoked response in man.

Contraction of the orbicularis oculi muscle in response to a sudden loud sound (acoustic startle response) and the N1/P2 component of the auditory evoked potential are both attenuated when a brief low-intensity stimulus is presented 30-500 ms before the 'startle-eliciting' stimulus (PPI). Here, we report the effects of the 'atypical' antipsychotic drug quetiapine and the 'conventional' antipsychotic haloperidol on these responses. Sixteen males (aged 19-38 years) participated in four sessions at 7-day intervals, in which they received quetiapine 12.5 mg, quetiapine 25 mg, haloperidol 3 mg and placebo, according to a balanced double-blind design. Electromyographic (EMG) responses of the orbicularis oculi muscle and N1/P2 auditory evoked potentials were recorded in a 20-min session, 2 h after treatment. Subjects received 40 trials in which 1-kHz sounds were presented: (i) 40 ms, 115 dB ('pulse alone' trials) and (ii) 40 ms, 85 dB, followed after 120 ms by 40 ms, 115 dB ('prepulse/pulse' trials). Mean amplitudes of the EMG response and the N1/P2 potential were derived from the pulse-alone trials and, in each case, percentage PPI was calculated. Serum prolactin was measured after each treatment, and autonomic (heart rate, blood pressure, salivation) and psychological (visual analogue self-ratings of mood and alertness, critical flicker fusion frequency) measures were taken before and after each treatment. Quetiapine 12.5 mg and 25 mg significantly reduced the amplitude of the EMG response without altering its inhibition by prepulses; haloperidol had no effect on EMG response amplitude or PPI. Neither drug affected N1/P2 amplitude or PPI of this response. Quetiapine, but not haloperidol, reduced subjective alertness and critical flicker fusion frequency. Haloperidol, but not quetiapine, elevated serum prolactin level. The ability of quetiapine to attenuate the startle response may reflect its sedative action.

Acoustic Stimulation↗
PubMed2002

Veterinary Products Committee working group report on feline and canine vaccination.

* The working group was set up by the Veterinary Products Committee in response to current concern in both the public domain and in the scientific community about possible health risks related to the routine vaccination of cats and dogs. The working group concluded that vaccination plays a very valuable role in the prevention and control of the major infectious diseases in cats and dogs. Although adverse reactions to vaccination, including lack of efficacy, occasionally occur, the working group concluded that the overall risk/benefit analysis strongly supports their continued use. * Although for some diseases there is evidence of a longer duration of immunity following vaccination than the one year which is typically recommended on the product literature, there is currently insufficient information to propose revaccination intervals other than those proposed by the manufacturer and approved by the regulatory process. * Notwithstanding this, in view of the occasional occurrence of adverse reactions, the working group recommends that the product literature indicates that the regime for booster vaccinations is based on a minimum duration of immunity rather than a maximum. The working group further recommends that the product literature should state that a risk/benefit assessment should be made for each individual animal by the veterinary surgeon in consultation with the owner with respect to the necessity for each vaccine and the frequency of its use. * The evidence suggests that cats appear to be susceptible to the occasional development of sarcomas at sites of injection and there is some further evidence to suggest that, although other products may be involved, this may be more associated with the use of vaccines containing aluminium-based adjuvants. The working group therefore recommends that a generic warning to this effect should appear on the product literature for all feline vaccines administered by injection. The working group also highlighted the need for professional and educational bodies in the UK to bring to the attention of veterinary practitioners appropriate methods for prevention, diagnosis and treatment of this serious condition. * The working group considered in depth the monitoring of adverse reactions, including the advantages and disadvantages of surveillance schemes. A range of options for carrying out further epidemiological (analytical) studies was also considered. However, the working group emphasised that surveillance schemes, and the UK Veterinary Medicines Directorate (VMD) Suspected Adverse Reaction (SAR) Surveillance Scheme in particular, provided a very valuable resource. The large database within the VMD scheme (collected since 1985) was analysed as part of this report. Figures were derived in terms of incidence (reporting rate) of certain clinical signs per 10,000 doses, and risk factors as identified by statistical analysis. However, due to a number of constraints, the analysis was not fully comprehensive and the interaction of possible risk factors was not determined. * Product-related control charts were developed in order to detect changes in incidence rates of adverse reactions (per 10,000 doses sold) both within and between different vaccines. Such charts provide a powerful way to detect changing trends in incidence and, when used in conjunction with product characteristics, they may identify possible causes. In general, the data showed that the incidence of adverse reactions to cat and dog vaccines per 10,000 doses of product sold was relatively low. Although under-reporting is a feature of such surveillance schemes, it does appear that, overall, vaccination of cats and dogs should be considered safe and effective. * Finally, the working group was conscious, while preparing this report, of the extensive media coverage that has been given to the issue of the safety of human vaccines, in particular the mumps, measles and rubella (MMR) vaccine. The working group emphasises that the conclusions and recommendations included in this report relate only to the vaccines used in cats and dogs. The issues identified are specific to the diseases and species examined and no attempt should be made to draw analogous conclusions in relation to vaccines administered to humans.

Animal Welfare↗
PubMed2002

Effects of ketanserin and haloperidol on prepulse inhibition of the acoustic startle (eyeblink) response and the N1/P2 auditory evoked response in man.

Contraction of the orbicularis oculi muscle in response to a sudden loud sound (acoustic startle response) and the N1/P2 component of the auditory evoked potential are both attenuated when a brief low-intensity stimulus is presented 30-500 ms before the 'startle-eliciting' stimulus (prepulse inhibition). Here, we report the effects of the serotonin (5-HT)2 receptor antagonist ketanserin and the D2 dopamine receptor blocking antipsychotic drug haloperidol on these responses. Fifteen males (aged 18-35 years) participated in four sessions at 7-day intervals, in which they received ketanserin 20 mg, ketanserin 40 mg, haloperidol 3 mg and placebo, according to a balanced double-blind design. Electromyographic (EMG) responses of the orbicularis oculi muscle and N1/P2 auditory evoked potentials were recorded in a 20-min session, 3 h after ingestion of haloperidol or 1 h after ingestion of ketanserin. Subjects received 40 trials in which 1-kHz sounds were presented: (i) 40 ms, 115 dB ('pulse alone' trials), and (ii) 40 ms, 85 dB, followed after 120 ms by 40 ms, 115 dB ('prepulse/pulse' trials). Mean amplitudes of the EMG response and the N1/P2 potential were derived from the pulse-alone trials and, in each case, percentage prepulse inhibition was calculated. Serum prolactin was measured after each treatment, and autonomic (heart rate, blood pressure, salivation) and psychological (visual analogue self-ratings of mood and alertness, critical flicker fusion frequency) measures were taken before and after each treatment. Ketanserin 40 mg significantly reduced the amplitude of the EMG response and both doses of ketanserin significantly suppressed prepulse inhibition of the response; haloperidol had no effect on EMG response amplitude or prepulse inhibition. Neither drug affected N1/P2 amplitude or prepulse inhibition of this response. Ketanserin, but not haloperidol, reduced subjective alertness and critical flicker fusion frequency. Haloperidol, but not ketanserin, elevated serum prolactin level. These results confirm that prepulse inhibition of the startle response and of the N1/P2 complex have different pharmacological sensitivities. The ability of ketanserin to attenuate the startle response may reflect its sedative action, as other drugs with sedative properties have also been found to attenuate the startle response in man. The ability of ketanserin to suppress prepulse inhibition of the startle response is consistent with previous evidence for the involvement of 5-HTergic mechanisms in the regulation of prepulse inhibition in man.

Acoustic Stimulation↗
PubMed2001

Bilateral movement enhances ipsilesional cortical activity in acute stroke: a pilot functional MRI study.

Functional MRI was performed in two acute stroke patients and six control subjects performing unilateral and bilateral repetitive gripping tasks. Patients were tested at three time points during recovery. Initially, bilateral movement enhanced activation in the primary motor cortex (M1) of the affected hemisphere compared with unilateral paretic hand movement. With recovery, activation of M1 in the affected hemisphere did not differ between unilateral paretic hand and bilateral movement. These preliminary data may have potential implications for acute stroke motor rehabilitation.

Acute Disease↗
PubMed2001

New devices to deliver somatosensory stimuli during functional MRI.

A new class of devices are described for improving investigation of somatosensory neuronal activation using fMRI. Dubbed magnetomechanical vibrotactile devices (MVDs), the principle of operation involves driving wire coils with small oscillatory currents in the large static magnetic field inherent to MRI scanners. The resulting Lorentz forces can be oriented to generate large vibrations that are easily converted to translational motions as large as several centimeters. Representative data demonstrate the flexibility of MVDs to generate different well-controlled vibratory and tactile stimuli to activate special proprioceptive and cutaneous somatosensory afferent pathways. The implications of these data are discussed with respect to the literature on existing devices for producing sensorimotor activation, as well as expanding the scope of current fMRI investigations.

Adult↗
PubMed2001

Magnetization transfer in MRI: a review.

This review describes magnetization transfer (MT) contrast in magnetic resonance imaging. A qualitative description of how MT works is provided along with experimental evidence that leads to a quantitative model for MT in tissues. The implementation of MT saturation in imaging sequences and the interpretation of the MT-induced signal change in terms of exchange processes and direct effects are presented. Finally, highlights of clinical uses of MT are outlined and future directions for investigation proposed.

Biophysical Phenomena↗
PubMed2001

Quantifying head motion associated with motor tasks used in fMRI.

In functional magnetic resonance imaging (fMRI) studies, long experiment times and small intensity changes associated with brain activation frequently lead to image artifacts due to head motion. Methods to minimize and correct for head motion by restraint, fast imaging, and retrospective image registration are typically combined but do not completely solve the problem, particularly for specific patient populations. As an initial step toward optimizing future designs of head restraints and improving motion correction techniques, the head motion characteristics of groups of stroke subjects, age-matched controls, and young adults were investigated with the aid of an MR simulator and a highly accurate position tracking system. Position measurements were recorded during motor tasks involving either the hand or the foot. Head motion was strongly dependent on the subject group and less upon the task conditions based on ANOVA calculations (P < 0.05). The stroke subjects exhibited approximately twice the head motion compared to that of age-matched controls, and the latter's head motion was about twice that of young adults. Moreover, the range of head motion in stroke subjects over all tasks was approximately 2 +/- 1 mm, with the motion occurring predominantly as translation in the superior-inferior direction and pitch rotation (nodding). These results lead to several recommendations on the design of fMRI motor experiments and suggest that improved motion correction strategies are required to examine such patient populations comprehensively.

Adult↗
PubMed2001

Effects of haloperidol and clozapine on prepulse inhibition of the acoustic startle response and the N1/P2 auditory evoked potential in man.

Contraction of the orbicularis oculi muscle in response to a sudden loud sound (acoustic startle response) and the N1/P2 component of the auditory evoked potential are both attenuated when a brief low-intensity stimulus is presented 30-500 ms before the 'startle-eliciting' stimulus (prepulse inhibition). Here, we report the effects of the 'conventional' antipsychotic drug haloperidol and the 'atypical' antipsychotic clozapine on these responses. Fifteen males (aged 19-54 years) participated in four sessions at 7-day intervals, in which they received clozapine 3 mg, clozapine 6 mg, haloperidol 3 mg and placebo, according to a balanced double-blind design. Electromyographic (EMG) responses of the orbicularis oculi muscle and N1/P2 auditory evoked potentials were recorded in a 20-min session, 3 h after treatment. Subjects received 40 trials in which 1-kHz sounds were presented: (i) 40 ms, 115 dB ('pulse alone' trials) and (ii) 40 ms, 85 dB, followed after 120 ms by 40 ms, 115 dB ('prepulse/pulse' trials). Mean amplitudes of the EMG response and the N1/P2 potential were derived from the pulse-alone trials and, in each case, percentage prepulse inhibition was calculated. Serum prolactin was measured after each treatment, and autonomic (heart rate, blood pressure, salivation) and psychological (visual analogue self-ratings of mood and alertness, critical flicker fusion frequency) measures were taken before and after each treatment. Clozapine 6 mg significantly reduced the amplitude of the EMG response without altering its inhibition by prepulses. Clozapine 6 mg did not affect the amplitude of the N1/P2 potential, but significantly attenuated prepulse inhibition of that response. Clozapine 3 mg and haloperidol had no significant effect on either response. Clozapine 3 mg and 6 mg, but not haloperidol, reduced subjective alertness and critical flicker fusion frequency. Clozapine 6 mg reduced salivation. Haloperidol, but not clozapine, elevated serum prolactin levels. These results confirm that prepulse inhibition of the startle response and of the N1/P2 complex have different pharmacological sensitivities. The abililty of clozapine to attenuate the startle response may reflect its sedative action. The basis of the abililty of clozapine to suppress prepulse inhibition of the N1/P2 potential remains uncertain.

Acoustic Stimulation↗
PubMed2000

Prevalence of Huntington disease in New South Wales in 1996.

OBJECTIVE: To estimate the prevalence of Huntington disease (HD) in New South Wales on Australian Census Day (6 August) 1996. DESIGN: Survey of records of the Huntington Disease Service and major hospitals, and of neurologists, psychiatrists, clinical geneticists and genetic counsellors. SUBJECTS AND SETTING: All patients in NSW who, on Census Day 1996, either had a definite diagnosis of HD (motor signs of chorea or ataxia and family history of HD or positive DNA test result) or would have had signs and later received a definite diagnosis (assessed 1 April 1997 to 1 July 1999). MAIN OUTCOME MEASURES: Prevalence (HD patients per 100,000 population); patient characteristics; year and basis of diagnosis. RESULTS: 380 patients with definite HD were identified, giving a prevalence of HD in NSW in 1996 of 6.29 per 100,000 population (95% CI, 5.68-6.96). A third of HD patients were aged 60 years or older. Diagnosis was confirmed by DNA testing for 171 patients (45%), including 30 (8%) with no recorded family history. Average numbers of new diagnoses per year were 11.8 (1984-1988), 21.8 (1989-1993) and 28.6 (1994-1998). Estimated number of people with a 50% risk of inheriting the HD mutation was 25.2 per 100,000 population. Estimated incidence of HD in 1996 was 0.65 per 100,000 population. CONCLUSIONS: Prevalence of HD in NSW is similar to estimated prevalence in other Australian and Western populations. Increasing numbers of cases are being diagnosed, and the 18 chronic care beds currently designated for HD patients in NSW are unlikely to be sufficient.

Adult↗
PubMed1999

Quantifying tissue damage due to focused ultrasound heating observed by MRI.

Focused ultrasound heating of ex vivo bovine kidney and liver was monitored using magnetic resonance imaging (MRI) to investigate the quantitative relationship between time-dependent temperature elevations and altered contrast in MR images due to thermal coagulation. Proton resonance frequency shift MR thermometry was performed during heating at 10 sec intervals (single-slice fast spoiled GRASS [FSPGR], theta/TE/TR 30 degrees/11/39 msec, field of view 8 cm, 256 x 256, 3 mm slice thickness, 1 NEX); post-heating MR images were T1-weighted (3D-FSPGR, theta/TE/TR 60 degrees/25/200 msec, 1 mm slice thickness, 3 NEX). Analysis of the resulting temperature versus time data using the Arrhenius relationship and a simple binary discrimination model showed that thermal coagulation occurred with heating at approximately 54 degrees C for 10 sec in both tissues and could be predicted with approximately 625 microm spatial resolution. These results suggest that quantitative MR guidance of thermal coagulation therapy is feasible, and they provide information useful for designing future investigations in vivo.

Animals↗
PubMed1999

Analysis of changes in MR properties of tissues after heat treatment.

To characterize changes in the MR parameters of tissues due to thermal coagulation, a series of T(1), T(2), diffusion, and magnetization transfer measurements were performed on a variety of ex vivo tissues: murine slow twitch skeletal muscle, murine cardiac muscle, murine cerebral hemisphere, bovine white matter, murine liver tissue, bovine retroperitoneal adipose tissue, hen egg white, human prostate and human blood. Standardized heat treatments were performed for each tissue type, over the temperature range from 37 degrees C to 90 degrees C. For all tissues, changes in each MR measurement resulting from thermal coagulation were observed above a threshold temperature of approximately 60 degrees C. These changes are explained based on biophysical knowledge of thermal damage mechanisms and the MR properties of normal tissues, and are particularly relevant for interpreting the changes in image contrast that are observed when MRI is used to guide and monitor thermal coagulation therapy procedures. Magn Reson Med 42:1061-1071, 1999.

Adipose Tissue↗
PubMed1999

Pulsed magnetization transfer imaging: evaluation of technique.

With use of an established physical model, numeric simulations were performed to evaluate current imaging protocols for the two primary applications of magnetization transfer: cerebral magnetic resonance angiography and neuroimaging of white matter disease. The authors found that the current technique is appropriate in the former but suboptimal in the latter. Further clinical investigations could potentially improve magnetization protocols for neuroimaging.

Animals↗