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Biomedical subjects

M F James

Publications and source records attributed to M F James.

At least 37 records · Page 2Linked to original sources

Pharmacological magnetic resonance imaging: a new application for functional MRI.

Various methods, including functional magnetic resonance imaging (fMRI), have recently been developed to allow investigators to study functional activity in the living brain. Such techniques are now being used to investigate regionally specific brain activity associated with the administration of CNS-active drugs. fMRI in particular is increasingly recognized as being a relatively non-invasive way to perform pharmacological investigations in experimental animals, healthy human volunteers, and individuals with CNS disease. This use of fMRI, dubbed 'pharmacological MRI' or 'phMRI', holds the promise of providing relatively straightforward pharmacodynamic assays and can be used to establish brain-penetrability parameters, or dose-ranging information for novel therapeutic compounds.

Anesthetics↗

Mapping of the cerebral response to hypoxia measured using graded asymmetric spin echo EPI.

Graded asymmetric spin echo-echo planar imaging (ASE-EPI) was used to measure transient alterations in cerebral oxygenation resulting from 60 seconds of anoxia in alpha-chloralose anaesthetised rats. The anoxic period induced a transient fall ( approximately 1 min) in signal intensity followed by a prolonged signal overshoot consistent with an autoregulatory response to oxygen deprivation. The magnitude of signal response, integrated over the entire brain, increased linearly with the echo asymmetry (t(ge)). However, that increase in sensitivity was offset by a reduced signal to noise ratio and quality of the image data. The responses of four regions of interest within the brain to the anoxic stimulus, and the effect of increasing the echo asymmetry, were compared. A comparable magnitude of signal decrease was observed in all brain regions except the superficial cortex that included pial vessels. As t(ge) was incremented differences in signal attenuation between regions became more pronounced. The signal overshoot observed upon restoration of normal breathing gases showed similar trends, producing similar normalised vascular responses for all regions of interest studied. Different regions of interest showed comparable time courses of the signal overshoot suggesting that similar autoregulatory vascular mechanisms operate in all brain regions. These findings additionally show that the use of graded ASE-EPI produced a characteristic profile of maximum signal change measured during and following the anoxic period for each brain region. They suggest that the shape of this profile was determined by the local vasculature within each region of interest; this feature could be exploited in activation studies to eliminate regions with significant signal changes originating from large draining vessels. Finally, the consistent physiological response observed, when the overshoot was compared to the magnitude of the signal drop, demonstrated that modification of the spin echo offset parameter did not mask or detrimentally alter the signal change resulting from the underlying physiological perturbation.

Animals↗

Porphyrias.

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Acute Disease↗

The effects on increasing cardiac output with adrenaline or isoprenaline on arterial haemoglobin oxygen saturation and shunt during one-lung ventilation.

Theoretically, if the cardiac output were increased in the presence of a given intrapulmonary shunt, the arterial haemoglobin oxygen saturation (SaO2) should improve as the venous oxygen extraction per ml of blood decreases. To test this hypothesis, eight pigs were subjected to one-lung ventilation and adrenaline and isoprenaline infusions used to increase the cardiac output. The mixed venous oxygen, shunt fraction and oxygen consumption were measured. With both adrenaline and isoprenaline, although there was a small rise in mixed venous oxygen content, there was a fall in SaO2. With adrenaline, the mean shunt rose from 48% to 65%, the mean oxygen consumption rose from 126 ml/min to 134 ml/min and the mean SaO2 fell from 86.9% to 82.5%. With isoprenaline, the mean shunt rose from 45% to 59%, the mean oxygen consumption rose from 121 ml/min to 137 ml/min and the mean SaO2 fell from 89.5% to 84.7%. It is concluded that potential improvement in SaO2, which might occur from a catecholamine-induced increase in mixed venous oxygen content during one-lung ventilation, is more than offset by increased shunting and oxygen consumption which reduce SaO2.

Adrenergic beta-Agonists↗

Can insertion length for a double-lumen endobronchial tube be predicted?

It has been suggested that the appropriate length of insertion for double-lumen tubes can be estimated by external measurement. This study examined the accuracy of external measurement in estimating the actual length of insertion required in 130 patients. It also examined the relationship between the length inserted and the patient's height in 126 patients and their weight in 125 patients. Although there was a fair correlation between the measured external length and the final inserted length (r = 0.61), the 95% confidence intervals of slope and intercept allowed a large variation and the prediction was too wide to be clinically useful. Height was reasonably well correlated with the final length (r = 0.51) but an equally wide 95% confidence interval rendered it of little clinical value. There was no correlation between weight and final tube length. It is concluded that external measurement alone is not adequate to predict a clinically acceptable position of the double-lumen tube.

Adolescent↗

Cortical spreading depression in the gyrencephalic feline brain studied by magnetic resonance imaging.

1.Time-lapse diffusion-weighted magnetic resonance imaging (DWI) was used to detect and characterize complex waves of cortical spreading depression (CSD) evoked with KCL placed upon the suprasylvian gyrus of anaesthetized cats. 2. The time-lapse representations successfully demonstrated primary CSD waves that propagated with elliptical wavefronts selectively over the ipsilateral cerebral hemispheres with a velocity of 3.8 +/- 0.70 mm min(-1) (mean +/- S.E.M. of 5 experiments). 3. In contrast, the succeeding secondary waves often remained within the originating gyrus, were slower (velocity 2.0 +/- 0.18 mm min(-1), more fragmented and varied in number. 4. Computed traces of the apparent diffusion coefficients (ADCs) showed negative deflections followed by monotonic decays (amplitudes: primary wave, -19.9 +/- 2.8%; subsequent waves, -13.6 +/- 1.9% duration at half-maximal decay, 150-200 s) when determined from regions of interest (ROIs) through which both primary and succeeding CSD waves propagated. 5. The passage of both the primary and the succeeding waves often correlated with transient DC potential deflections recorded from the suprasylvian gyrus. 6. The detailed waveforms of the ADC and the T2*-weighted (blood oxygenation level-dependent: BOLD) traces showed a clear reciprocal correlation. These imaging features that reflect disturbances in cellular water balance agree closely with BOLD measurements that followed the propagation velocities of the first and subsequent CSD events. They also provide a close physiological correlate for clinical observations of cortical blood flow disturbances associated with human migraine.

Anesthesia↗

Eltanolone (5-beta-pregnanolone) does not trigger, and attenuates halothane triggering of, malignant hyperthermia in malignant hyperthermia susceptible swine.

Eltanolone is the lipid emulsion formulation, for intravenous use, of the steroid anaesthetic 5-beta-pregnanolone. We have screened this agent in malignant hyperthermia susceptible (MHS) Landrace swine to assess its potential to trigger the Malignant Hyperthermia (MH) syndrome in MHS subjects or to influence halothane triggering of MH in such patients. Administered in anaesthetic concentration, eltanolone did not trigger the MH syndrome in MHS swine. When co-administered in low dosage with halothane, the drug prevented initiation of the MH syndrome in four of eight pigs and attenuated its progress in the remainder.

Anesthetics, Inhalation↗

The effect of eltanolone on pulmonary vascular resistance in landrace swine.

This paper reports on the haemodynamic effects of eltanolone observed in Landrace swine during the investigation of the drug with respect to safety in malignant hyperthermia-susceptible individuals. Pigs were sedated with intramuscular ketamine, followed by induction of anaesthesia employing thiopentone administered via an ear-vein. After intubation, anaesthesia was maintained using nitrous oxide in oxygen. A total of eight pigs were then further anaesthetised on two separate occasions using one of two dose schedules. A bolus of 1.5 mg kg(-1) of eltanolone was administered, followed by a continuous infusion at either 2 or 10 mg kg(-1) h(-1). There were no significant changes in heart rate, mean arterial pressure, cardiac output or systemic vascular resistance following eltanolone. In all cases eltanolone induced marked rises in pulmonary artery pressure and pulmonary vascular resistance (P<0.01) at all measuring points and in right ventricular stroke work at 6-10 min after drug exposure. We conclude that the selective influence of eltanolone on the pulmonary vasculature is probably species-specific, but may have clinical significance in patients with pulmonary hypertension.

Animals↗

A study of rotationally invariant and symmetric indices of diffusion anisotropy.

This study investigated the properties of a class of rotationally invariant and symmetric (relative to the principal diffusivities) indices of the anisotropy of water self-diffusion, namely fractional anisotropy (FA), relative anisotropy (RA), and volume ratio (VR), with particular emphasis to their measurement in brain tissues. A simplified theoretical analysis predicted significant differences in the sensitivities of the anisotropy indices (AI) over the distribution of the principal diffusivities. Computer simulations were used to investigate the effects on AI image quality of three magnetic resonance (MR) diffusion tensor imaging (DTI) acquisition schemes, one being novel: the schemes were simulated on cerebral model fibres varying in shape and spatial orientation. The theoretical predictions and the results of the simulations were corroborated by experimentally determined spatial maps of the AI in a normal feline brain in vivo. We found that FA mapped diffusion anisotropy with the greatest detail and SNR whereas VR provided the strongest contrast between low- and high-anisotropy areas at the expense of increased noise contamination and decreased resolution in anisotropic regions. RA proved intermediate in quality. By sampling the space of the effective diffusion ellipsoid more densely and uniformly and requiring the same total imaging time as the published schemes, the novel DTI scheme achieved greater rotational invariance than the published schemes, with improved noise characteristics, resulting in improved image quality of the AI examined. Our findings suggest that significant improvements in diffusion anisotropy mapping are possible and provide criteria for the selection of the most appropriate AI for a particular application.

Animals↗

Effect of 20% in vitro haemodilution with warmed buffered salt solution and cerebrospinal fluid on coagulation.

We have conducted an in vitro coagulation study consisting of two separate groups of 20 subjects using the thrombelastograph. In the first group, haemodilution was performed with a physiological balanced salt solution similar to plasma, with the exception of calcium, and buffered to a normal pH (Plasmalyte B) at 37 degrees C on blood obtained from consenting volunteers. In the second group, a protein-poor body fluid (cerebrospinal fluid (CSF)) obtained from parturient patients undergoing spinal anaesthesia for Caesarean section was used as the diluent. There were statistically significant differences between the warmed Plasmalyte B treated samples and their untreated controls for all variables measured by the thrombelastograph, except for maximum amplitude, and between the CSF treated samples and their untreated controls for all variables. We conclude that electrolyte and acid-base composition of the diluent fluid had no effect on the observation that crystalloid haemodilution produces hypercoagulability. The marked increase in coagulability produced by addition of CSF cannot be explained on a simple haemodilution basis and confirms previous suggestions of the presence of a procoagulant factor in CSF.

Blood Coagulation↗

Pro-coagulant effect of in vitro haemodilution is not inhibited by aspirin.

We have conducted an in vitro coagulation study, using the thrombelastograph (TEG), to determine if the enhanced coagulability of whole blood after haemodilution with normal saline can still be demonstrated after administration of an antiplatelet agent. Aspirin inhibits the platelet-endothelial interaction that is part of the coagulation process. We investigated the role of aspirin in the phenomenon of haemodilution-induced coagulability to identify if the platelet-endothelial system is involved in the process. Previous work showed that the TEG is not altered by oral ingestion of aspirin. Blood from 20 volunteers was divided into two aliquots of 4 ml each. One sample was diluted by 20% by addition of 0.9% saline 1 ml while the other was not diluted and served as a control. Coagulation studies were performed using the TEG and enhanced coagulation was seen in the saline diluted samples. Subjects then received soluble aspirin 375 mg daily for 3 days, after which the tests were repeated. There was no difference in the control TEG values and saline enhancement of coagulation was preserved in all subjects after 3 days of aspirin administration. We conclude that aspirin had no effect on the observation that haemodilution with saline enhances the coagulability of whole blood.

Aspirin↗

Nitrous oxide: still useful in the year 2000?

The risk-benefit ratio of using nitrous oxide has been debated for many years. In this article the adverse effects of nitrous oxide on patient well-being, including its role in postoperative nausea and vomiting, its toxic effects and adverse physiological changes are reviewed. Guidelines for the rational use of the drug are suggested.

Journal Article↗

The effect of magnesium sulfate on cerebral blood flow velocity, cardiovascular variables, and arterial carbon dioxide tension in awake sheep.

Although there are data demonstrating reversal of cerebral vasospasm with magnesium sulfate, there is little information on the effects of magnesium on the normal intact cerebral vasculature. This study investigated the actions of magnesium on cerebral blood flow (CBF) velocity, cardiovascular variables, and arterial gas tensions. Magnesium sulfate was infused into awake, adult sheep at rates of 3 and 6 mmol/min to a total of 15 and 30 mmol, respectively. Direct arterial pressure, cardiac output, and CBF velocity were measured using chronically implanted catheters and a sagittal sinus Doppler flow probe. Arterial blood was sampled for magnesium concentrations and blood gas analysis. Infusion of both 15 and 30 mmol of magnesium increased CBF velocity by 14% (P = .056) and 24% (P = .023), respectively. These increases were accompanied by increases in arterial carbon dioxide tension (PaCO2) of 12% (P = .033) and 17% (P = .048). Multiple linear regression analysis revealed that both PaCO2 (P = .00037) and magnesium (P = .0012) were important predictors of CBF velocity.

Animals↗

Anaesthesia of the common marmoset (Callithrix jacchus) using continuous intravenous infusion of alphaxalone/alphadalone.

A safe means of anaesthetizing common marmosets (Callithrix jacchus) for a study using magnetic resonance imaging (MRI) to investigate cerebral ischaemia was required. Continuous infusion of alphaxalone/alphadalone was used to anaesthetize 37 marmosets for non-recovery and recovery experiments. This was found to give safe, reliable anaesthesia when coupled with pulse oximetry and electrocardiographic (ECG) monitoring.

Alfaxalone Alfadolone Mixture↗

The role of the College of Medicine of South Africa Diploma in Anaesthesia in southern Africa.

OBJECTIVE: To determine the role that the College of Medicine Diploma in Anaesthesia (DA) plays in health services in southern Africa. DESIGN: A postal questionnaire. MAIN INFORMATION SOUGHT: Reasons for doing the DA, percentage of diplomates still actively involved in anaesthesia, career pathways of diplomates, perceived value of the DA, geography and type of anaesthetic practice of diplomates, and participation in continuing medical education. SUBJECTS: The 1,096 candidates who passed the DA between 1974 and 1993. METHODS: Questionnaires were sent to all 861 diplomates with known addresses. RESULTS: The response rate was 62.1% (535/861). Over 70% of diplomates are still actively involved in anaesthesia. Approximately one-third of all diplomates specialize in anaesthesia. The majority of GP anaesthetists with the DA have trained in anaesthesia for more than 1 year. Thirty-three per cent of GP anaesthetists work in small towns or rural areas. Nearly 20% of GP anaesthetists spend more than 75% of their time in anaesthetic practice. Twenty-eight diplomates are working in southern African countries outside South Africa. The DA is perceived to have been of value by the majority of specialist and non-specialist diplomates. CONCLUSIONS: Diplomates are playing a valuable role in anaesthesia throughout the southern African region.

Adult↗