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Biomedical subjects

R D Jones

Publications and source records attributed to R D Jones.

At least 73 records · Page 4Linked to original sources

Inhibition of hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries by diphenyleneiodonium (DPI).

The NADPH oxidase inhibitor, diphenyleneiodonium (DPI), is known to selectively inhibit hypoxic pulmonary vasoconstriction (HPV) in isolated rat and rabbit lungs. We have investigated whether DPI has similar effects in rat pulmonary arteries in vitro. Vessels (n=38, internal diameters 327+/-41 microM) were mounted in an automated myograph and preconstricted with prostaglandin F2alpha (PGF2alpha, 5 microM) before an acute hypoxic challenge. The effects of DPI (10 microM), or the vehicle DMSO, were studied on the first contractile phase of HPV. DPI (10 microM) was found to significantly inhibit HPV; 1.83+/-0.42 mN/mm (pre-DPI) compared to 0.11+/-0.22 mN/mm (post-DPI,P<0.01). However, the vehicle DMSO (0.2%) also resulted in a reduction of HPV, although this was significantly different from inhibition via DPI (P<0.05), implying a DPI-sensitive component. The effects of DPI (0.1-300 microM) were also studied on the second contractile phase of HPV. DPI (300 microM) caused a significant reversal of 45% (0.50-0.27 mN/mm) compared to 9% reversal (0.38-0.35 mN/mm) seen with DMSO (P<0.0001). The fact that an inhibitor of NADPH oxidase, the enzyme responsible for producing reactive oxygen species from oxygen, attenuated the pulmonary vascular response to hypoxia, may indicate that this, or a similar, enzyme is involved in oxygen sensing.

Animals↗

Validation of air as an equilibration medium in gastric tonometry: an in vitro evaluation of two techniques for measuring air PCO2.

This laboratory-based bench study was undertaken to evaluate the accuracy and equilibration characteristics of air and saline respectively as CO2 equilibrating media in the silicone balloon of a gastric tonometer and to compare two methods of measuring air PCO2. Two gastric tonometers were suspended in a bath containing 0.9% saline maintained at 37 degrees C. Certified calibration gases at three different CO2 concentrations were bubbled into the bath. When the bath PCO2 measurement was stable the tonometers were primed with 5 ml of air and 2.5 ml normal saline respectively and allowed to equilibrate for 30 and 90 minutes. Following equilibration, samples were aspirated and analysed in duplicate in a blood gas analyser. Bias and precision were calculated from the measured and expected PCO2 values. A consistent negative bias (21-23%) was seen with air at all three CO2 concentrations at 30 and 90 minutes with a coefficient of variation between 2.7 and 3.3%. Imprecise data were obtained with saline at different levels of CO2. A similar experimental set-up was used to compare air PCO2 measurement by a blood gas analyser and an infra-red analyser (Tonocap). Similar bias was obtained with the blood gas analyser with respect to air PCO2 measurement as in experiment 1. The infra-red analyser measurement was highly precise with negligible bias. Air appears to be a better CO2 equilibration medium during bench testing of tonometry producing a systematic negative offset and requiring a uniform correction factor of 1.25. This correction factor is independent of equilibration time and equilibrating CO2 concentration. The use of the infra-red analyser eliminates any bias in the measurement of air PCO2 and obviates the need for a correction factor.

Air↗

Letter and semantic fluency in Alzheimer's, Huntington's, and Parkinson's dementias.

A pattern of semantic fluency worse than letter fluency has been presented as evidence of impaired semantic networks in "cortical" dementias (e.g., Alzheimer's disease), distinguishing them from "subcortical" dementias (e.g., Parkinson's disease, Huntington's disease). However, there have been few systematic studies of this propositions. The present study compared Alzheimer's, Parkinson's, and Huntington's disease subjects with mild dementia to each other and to matched normal controls on letter and semantic fluency tasks. Results revealed parallel semantic/letter fluency patterns for all groups, suggesting that there is no unique pattern of semantic/letter fluency deficits for "cortical" or "subcortical" dementias. Qualitative errors (repetitions, intrusions) were also evaluated. Huntington's subjects had significantly more repetition errors than all other groups, and Alzheimer's subjects had significantly more repetition errors than Parkinson's subjects and normal controls. There were no differences in number of intrusion errors. Findings suggest that semantic fluency deficits are not unique to Alzheimer's dementia and may not help to differentiate between different etiologies of dementia.

Journal Article↗

The effect of hydrogen peroxide on hypoxia, prostaglandin F2 alpha and potassium chloride induced contractions in isolated rat pulmonary arteries.

We have investigated the action of the product of the enzyme NADPH oxidase; hydrogen peroxide (H2O2), on the first phase of the hypoxic contraction, prostaglandin F2 alpha (PGF2 alpha)-induced contractions and potassium chloride (KCl)-induced contractions, in isolated rat pulmonary arteries in a wire myograph. Both concentrations of H2O2 (0.03 and 0.5 mM) produced initial contractions, and the higher concentration of H2O2 produced a significant inhibition of both the priming concentration of PGF2 alpha (5 microM) and the hypoxic contraction (P < 0.01 for both contractions). These effects were shown to be reversible, with contractions of a similar size to control values being seen to both PGF2 alpha (5 microM) and hypoxia following washout of H2O2 (P > 0.1 for both contractions). H2O2 (0.03 mM) was shown to have no significant effect upon either contraction (P > 0.1 for both contractions). H2O2 (0.5 mM) was also shown to have a significant inhibitory effect upon the efficacy (Emax) of the PGF2 alpha and KCl concentration-response curves (P < 0.01 for both contractions). This inhibition was again shown to be reversible. The higher concentration of H2O2 (0.5 mM) is clearly shown to be having a dual action, producing an initial contraction followed by inhibition of contractions to both PGF2 alpha and KCl. The mechanism by which H2O2 produces vasoconstriction is unclear, but it is suggested that H2O2 may inhibit the release of Ca2+ ions from intracellular stores as this is a common link between the modes of action of these two contractile agents. In addition to this, as an elevation in intracellular Ca2+ from intracellular stores appears to be a prerequisite for hypoxic pulmonary vasoconstriction (HPV), then this apparent mode of action of H2O2 could play an important role in the regulation of HPV and suggests a possible role for NADPH oxidase or a similar oxidoreductase as an oxygen sensor.

Animals↗

WCALive: broadcasting a major medical conference on the Internet.

Live video and sound from the 11th World Congress of Anaesthesiology in Sydney, Australia were broadcast over the Internet using the CuSeeme software package as part of an ongoing evaluation of Internet-based telecommunication in the delivery of Continuing Medical Education (CME). This was the first time such a broadcast had been attempted from a medical convention. The broadcast lasted for four days, during which a functioning combination of computer hardware and software was established. Technical issues relating to broadcast of these real time signals over ISDN links and the Internet itself were addressed. Over 200 anaesthetists from around the world were able to 'attend' the plenary sessions via the Internet. Evidenced by feedback received audio reception was quite good. Video reception was less successful for those receiving the broadcast via a modem based Internet connection. The received signal in such circumstances was adequate to provide a video presence of the speaker but inadequate to allow details of 35 mm slides to be visualised. We conclude that this technology will be of use in the delivery of CME materials to remote areas provided simultaneous viewing of high resolution still images is possible using another medium, such as the World Wide Web.

Anesthesiology↗

Multireference adaptive noise canceling applied to the EEG.

The technique of multireference adaptive noise canceling (MRANC) is applied to enhance transient nonstationarities in the electroeancephalogram (EEG), with the adaptation implemented by means of a multilayer-perception artificial neural network (ANN). The method was applied to recorded EEG segments and the performance on documented nonstationarities recorded. The results show that the neural network (nonlinear) gives an improvement in performance (i.e., signal-to-noise ratio (SNR) of the nonstationarities) compared to a linear implementation of MRANC. In both cases an improvement in the SNR was obtained. The advantage of the spatial filtering aspect of MRANC is highlighted when the performance of MRANC is compared to that of the inverse auto-regressive filtering of the EEG, a purely temporal filter.

Algorithms↗

Motor power pharmacodynamics of subarachnoid hyperbaric 5% lidocaine in the sitting position.

BACKGROUND: Repetitive dynamometric measurement using a plantar flexion power device (PFPD) provides detailed data describing the onset and offset of motor block following spinal administration of lidocaine. The aim of this study was to evaluate administration of two doses of spinal lidocaine in the sitting position to determine whether our dynamometric model produces data consistent with our current understanding of the pharmacokinetics of subarachnoid, hyperbaric, 5% lidocaine. METHODS: Twenty male patients (54 to 80 yr) undergoing cystoscopy received spinal anaesthesia with either 75 mg (n = 10) or 100 mg of hyperbaric lidocaine 5%, in the sitting position, under standardised conditions. Plantar flexion muscle power was recorded during onset and offset of anaesthesia using a load cell interfaced with a computer (PFPD). RESULTS: Onset of paralysis following spinal block in the sitting position was rapid and complete with motor power declining exponentially to 5% of preoperative values by 8.5 min in all patients. There was no difference in decay or recovery of plantar flexion motor power data between dosage groups in the sitting position. Measurement using the PFPD shows that onset of motor paralysis is described by an exponential decay and that motor recovery occurs at a fixed rate. Extent of block to cold and pinprick was similar in both dosage groups in the sitting position (median T4). CONCLUSION: This study shows that in the sitting position, doses less than 75 mg of 5% hyperbaric lidocaine are required to significantly improve ambulatory times.

Aged↗

Physicochemical compatibility of propofol with thiopental sodium.

The physicochemical compatibility of propofol and thiopental sodium when mixed together in various ratios and stored was studied. Mixtures of propofol and thiopental sodium in five volume ratios from 1:3 to 3:1 were refrigerated (4 degrees C) for up to seven days and then centrifuged at 2000g for two hours. Droplet sizes were determined at intervals by optical microscopy and laser diffraction, and chemical stability of the 1:1 mixture was evaluated by high-performance liquid chromatography (HPLC). Optical microscopy and laser diffraction indicated negligible changes in droplet size within 48 hours of mixing. A small increase in the width of the frequency distribution of droplet sizes occurred 24-48 hours after mixing for the two mixtures with the lowest propofol concentration. Some coalescence of droplets occurred on centrifugation. These results indicated negligible formation of droplets that might cause embolism after i.v. injection of fresh mixtures (not more than six hours old). A yellow color appearing after 24-48 hours indicated anticipated chemical changes. HPLC of samples stored at 25 degrees C indicated clinically unimportant drug loss after six hours. The mixtures were considered physically stable for not more than 48 hours. Droplet size in mixtures of propofol and thiopental sodium did not increase until at least 24 hours. Drug loss from mixtures containing propofol 5 mg/mL and thiopental sodium 12.5 mg/mL was insignificant for up to eight hours.

Anesthetics, Intravenous↗

A technique for removal of the visuoperceptual component from tracking performance and its application to Parkinson's disease.

Although it is well established that subjects with Parkinson's disease perform poorly on complex sensory-motor tasks, the extent to which this is due to visuoperceptual deficits is unclear. We measured the performance of 16 patients with Parkinson's disease, both on and off drugs, and 16 age and sex matched control subjects on preview and nonpreview tracking tasks and a nonmotor test of dynamic visuoperception. Order effects were controlled for by a randomized cross-over design. Performance on the perceptual task was measured in terms of perceptual resolution and was found impaired in the Parkinsonian group. The contribution of visuoperceptual function to tracking performance was removed using the concept of a visuoperceptual buffer-zone. The mean tracking error remained impaired on all tracking tasks and demonstrated that limitations is visuoperceptual function play only a minor role in the tracking errors in both Parkinsonian and control subjects. It is clear that the technique for determining the visuoperceptual component of performance on complex sensory-motor tasks has considerable scope for application in studies of a variety of brain disorders.

Adult↗

Patient-controlled alfentanil. Target-controlled infusion for postoperative analgesia.

We have compared the opioid effects of a patient-demand, target-controlled infusion of alfentanil (n = 10), with patient-controlled bolus administration of morphine (n = 10) following major spinal surgery in Chinese patients aged from 11 to 67 years. The same general anaesthesia regimen was used in all patients. One group of patients were given intra-operative morphine analgesia followed by postoperative intravenous morphine patient-controlled analgesia, while the other group received an intra-operative target-controlled infusion of alfentanil. Following surgery, the alfentanil group were given control of a handset and were able to increase the target alfentanil plasma level in 5 ng.ml-1 increments with a 2-min lockout interval. If analgesia was not demanded within a 15-min period, the computer reduced the target concentration by 5 ng.ml-1. All patients had continuous pulse oximetry monitoring and hourly recording of pain, sedation, nausea scores and respiratory rate. Patients receiving alfentanil had the target concentration noted hourly and four blood samples taken during the first 24 h for measurement of plasma alfentanil concentrations by high performance liquid chromatography. The alfentanil infusion system was equally effective as an analgesic technique when compared with morphine patient-controlled analgesia. There were no hypoxaemic episodes (oxygen saturation < 94%), no difference in sedation scores and the incidence of nausea (30%) was the same in both groups. There was a significantly (p < 0.001) lower respiratory rate in the alfentanil group compared with patients receiving morphine at, clinically assessed, equianalgesia. The predicted plasma alfentanil concentrations increased rapidly from about 30 ng.ml-1 during the first 4 h to around 100 ng.ml-1 at the end of the 24-h study period. The precision of the target-controlled infusion system was 75.4% and the mean prediction error (bias) 58.1%, suggesting an underestimation of the measured alfentanil concentrations by the alfentanil infusion system in these Chinese patients.

Adolescent↗

Pharmacodynamics of subarachnoid hyperbaric 5% lignocaine.

Twenty male patients (55 to 85 yr) undergoing cystoscopy received spinal anaesthesia with either 75 mg (n = 10) or 100 mg of hyperbaric lignocaine 5% under standardised conditions. Plantar flexion muscle power was recorded during onset and offset of anaesthesia using a load cell interfaced with a computer (PFPD) and these data were compared with intermittent clinical assessments of spinal anaesthesia. Onset of paralysis was rapid and complete with motor power declining exponentially to 5% of preoperative values by 5 minutes in all patients. Extent of block to cold and pinprick was similar in both dosage groups (median T4), as was the rate of block onset. Block regression was complete by three hours in all patients and restitution of plantar flexion motor power was associated with normal thermosensibility at L1 and recovery of the patient's ability to walk and micturate. Recovery of plantar flexion motor power occurred at 95.5 +/- 7.38 min in patients given 75 mg compared with 129 +/- 9.5 min in those given 100 mg lignocaine (P < 0.05). The time between onset and full motor recovery in the 75 mg group (7.2 +/- 1.2 min) was less than the 100 mg lignocaine group (29 +/- 5.1 min) (P < 0.001). The larger dose of lignocaine did not confer any clinical advantage in block onset or intensity and made the onset of recovery less predictable. The Bromage grading, while clinically appropriate during anaesthesia onset, does not provide data relating to the density of block and the PFPD was therefore useful for describing the anaesthesia recovery phase.

Aged↗

Method for screening drug and chemical effects in laboratory rats using computerized quantitative electroencephalography.

A minimally-invasive method of quantitative electroencephalography (qEEG) that requires no anesthetics and parallels techniques of naturalistic stimulation was developed and validated for regulatory testing of drugs and chemicals in rats. Male and female Fischer 344 rats were utilized in a randomized-block design to measure qEEG target parameters associated with a range of cholinesterase inhibition. For this study, physostigmine was administered ip at doses of 0.05, 0.2 or 1.0 mg/kg, resulting in average cholinesterase inhibition in plasma (28, 38 and 70%), erythrocytes (19, 24 and 36%), and brain (2, 10 and 31%) which correlated well with increased total power and amplitude changes. Additional treatment-related effects consisted of decreased relative alpha and beta, increased relative delta, and a left-shift in the spectral-edge frequency. In a second study, male and female Sprague-Dawley rats were utilized in a treatment-by-subjects design to determine qEEG target parameter changes due to the M2 autoreceptor agonist oxotremorine. Repeated incremental doses (0.05, 0.1, 0.2 mg/kg; ip) of oxotremorine resulted in increased beta contribution, a right-shift in the spectral-edge frequency and decreased alpha contribution. These qEEG results with physostigmine and oxotremorine correlate well with receptor-specific and general muscarinic effects, making it a reliable contribution to analysis of agonist and antagonist effects of cholinergic compounds.

Analysis of Variance↗

EEG spectral topography in neurology: I. A review of techniques.

As researchers investigate methods of automated interpretation of the electroencephalogram (EEG), spectral topography is emerging as an important and popular technique in applied clinical neurophysiology. Several computer-based EEG topography systems have been developed to produce topographic maps showing the spatial distributions of pre-defined frequency bands in the EEG. However, there is ongoing debate as to which technical approaches to EEG topography generate maps that can be most accurately interpreted by clinicians. This paper reviews existing topographic techniques, particularly as they apply to diagnostic neurology, and discusses some of the technical choices that must be addressed by topography users. These choices include the selection of montage, epoch length, interpolation scheme, graphical display method, and artifact removal technique. The points summarised here highlight the general opinion that although EEG topography has many benefits, it should be invoked with care and the user should possess an indepth understanding of the procedures used to produce the topographic maps.

Biomedical Engineering↗