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Biomedical subjects

R D Jones

Publications and source records attributed to R D Jones.

At least 91 records · Page 5Linked to original sources

EEG spectral topography in neurology: II. A new system and a theoretical comparison of interpolation techniques.

An EEG spectral topography system has been developed to produce maps of the time-averaged spectra of a 16-channel EEG. The design of this system is based upon the discussions of the contentious issues of topography presented in Part I and a theoretical study of two-dimensional interpolation techniques. The comparison of techniques is based upon simulated electric fields on a three-layer spherical head model. Four two-dimensional interpolation techniques are investigated: bilinear, nearest neighbour, bicubic splines, and thin-plate splines. The most accurate method, a 2nd degree thin-plate spline, is employed in the new topography system. The EEG spectral topography system adopts the following procedures: the EEG is recorded using the 16 channel ipsilateral-ears montage; spectral analysis is applied to several overlapping epochs, relatively free of artifacts, of length 5.12 s; the averaged frequency spectrum is divided into specified frequency bands; for each channel, the average spectral component of each band is mapped onto a plane representing the head; and the maps are completed using 2nd degree thin-plate spline interpolation. A particular aim of the development was to produce a topography system compatible with the present EEG recording system at Christchurch Hospital. This has been achieved and, consequently, the topography system is of immediate clinical use. The system is currently part of a major clinical study.

Biomedical Engineering↗

The effects of physostigmine on the electroretinogram in the beagle dog.

The purpose of the study was to correlate electroretinogram (ERG) parameters with increasing levels of plasma, erythrocyte and ocular tissue cholinesterase inhibition using the beagle dog as a model for human neurovisual toxicity. The anticholinesterase compound physostigmine was administered at various steady-state intravenous infusion rates based on pharmacokinetic estimates of plasma and red blood cell cholinesterase inhibition. The most sensitive parameter was the b-wave amplitude of the rod response, which was significantly depressed compared to pretreatment at all levels of acute cholinesterase depression. The overall maximal ERG response demonstrated a trend of declining a- and b-wave amplitudes, which corresponded with the increased levels of cholinesterase depression, but these differences were not significant. The depression of the electroretinogram rod and cone amplitudes appeared to parallel plasma cholinesterase inhibition more closely than erythrocyte cholinesterase activity. Ocular tissue cholinesterase activity was significantly depressed in the retina (70%), cornea (60%) and dorsal rectus extraocular muscle (46%). Electroretinography may be a useful physiological tool for evaluating the ocular toxicity of certain chemicals or pharmaceuticals associated with cholinesterase biomarker activity.

Animals↗

Fractionation of visuoperceptual dysfunction in Parkinson's disease.

There is considerable evidence that visuoperceptual function is impaired in Parkinson's disease although this view remains contentious. The issue is confounded by studies which have demonstrated impairment of visual sensation, in particular high-contrast visual acuity, in Parkinson's disease. We have measured the visuoperceptual performance of 16 patients with mild to moderate Parkinson's disease, both on and off drugs, and 16 age and sex matched control subjects on non-motor tests of visual resolution, static perception, and dynamic perception. Performance on the perceptual tasks was measured in terms of perceptual resolutions and was found impaired in the parkinsonian group. After removal of the contribution of poorer visual resolution, the overall visual perception remained impaired, although to a relatively subtle degree, such that the difference between the two groups on its static and dynamic components did not reach significance.

Adult↗

Amplification of the amoA Gene from Diverse Species of Ammonium-Oxidizing Bacteria and from an Indigenous Bacterial Population from Seawater.

Vol. 61, no. 7, p. 2705, column 2, lines 9 to 16: these sentences should read as follows. "These two sequences show 75% identity at the DNA level to the published N. europaea sequence and show 85% identity to each other. Interestingly, the regions that our primers were designed to target show 5 and 3 mismatches with the Nitrosospira sequence and 2 and 2 mismatches with the Nitrosolobus sequence for the forward and reverse primers, respectively." [This corrects the article on p. 2702 in vol. 61.].

Journal Article↗

Amplification of the amoA gene from diverse species of ammonium-oxidizing bacteria and from an indigenous bacterial population from seawater.

Because the chemolithotrophic ammonium-oxidizing bacteria are an integral component of nitrogen biogeochemistry, a sensitive and accurate method to detect this ecologically important group of microorganisms is needed. The amoA gene of these organisms encodes the active site of ammonia monooxygenase, an enzyme unique to this group of nitrifying bacteria. We report here the use of the PCR technique to detect the amoA gene from pure cultures of chemolithotrophic ammonium-oxidizing bacteria, ammonium oxidizers introduced into filtered seawater, and the natural bacterial population of an unfiltered seawater sample. Oligonucleotide primers, based on the published amoA sequence from Nitrosomonas europaea, were used to amplify DNA from pure cultures of Nitrosomonas europaea, Nitrosomonas cryotolerans, and Nitrosococcus oceanus and from bacteria in seawater collected offshore near the Florida Keys. Partial sequencing of the amplification products verified that they were amoA. These primers, used in conjunction with a radiolabeled amoA gene probe from Nitrosomonas europaea, could detect Nitrosococcus oceanus inoculated into filter-sterilized seawater at 10(4) cells liter-1. Native marine bacteria containing amoA could also be detected at their naturally occurring titer in oligotrophic seawater. Amplification of the gene for ammonia monooxygenase may provide a method to estimate the distribution and relative abundance of chemolithotrophic ammonium-oxidizing bacteria in the environment.

Ammonia↗

Siggaard-Andersen algorithm-derived p50 parameters: perturbation by abnormal hemoglobin-oxygen affinity and acid-base disturbances.

The p50 and derived indexes, calculated by using the Siggaard-Andersen algorithm from a single measurement of arterial blood gas tensions and hemoglobin-oxygen saturation, are used to assess tissue oxygen availability in critical illness. We tested the accuracy of the Siggaard-Andersen p50 algorithm over a wide range of pathophysiologic conditions. Blood gases, cooximetry, and calculation of standard and in vivo p50 were performed at multiple saturations, CO2 tensions, and H+ concentrations on blood with normal (standard p50 of 26.1 and 26.7 mm Hg), increased (19.0 and 25.4), and reduced (33.9 and 38.2) hemoglobin-oxygen affinity, as well as on high-affinity blood from two patients with diabetic ketoacidosis (16.7 and 20.8). Log p50 in vivo/pH plots were constructed to determine the Bohr effect. Except in the normal affinity specimens (coefficient of variation < 1.7%), standard p50 values showed high variability (coefficient of variation > 5.9%), with saturation-linked bias and distortion of the Bohr effect. Standard p50 was overestimated by up to 11 mm Hg as saturation approached 97%. Although base deficit correction of the stored specimens (6.9 < pH < 7.1) restored the Bohr effect and improved the accuracy of standard p50 calculations (coefficient of variation = 4.4% and 2.9%), saturation-linked bias persisted. We conclude that Siggaard-Andersen p50 calculations may be misleading when there are disturbances of hemoglobin-oxygen affinity and acid-base balance, owing to changes in shape of the hemoglobin-dissociation curve. When metabolic acidosis occurs with high hemoglobin-oxygen affinity, as can occur in critical illness, indexes derived by the Siggaard-Andersen algorithm on arterial blood may greatly overestimate oxygen availability.

Acid-Base Imbalance↗

Peri-operative administration of rectal diclofenac sodium. The effect on renal function in patients undergoing minor orthopaedic surgery.

In a randomized, double-blind study, we administered placebo and diclofenac sodium 100 mg suppositories 1 h pre-operatively and on the first post-operative morning to 22 adult patients undergoing minor orthopaedic surgery. A standardized post-operative intravenous fluid regimen was instituted until oral fluids were tolerated. Renal function was assessed pre-operatively, and on the first and second post-operative days by the measurement of urine output, creatinine, urea, sodium, potassium and NAG (N-acetyl-b-D-glucosaminidase) levels and serum creatinine, urea, sodium and potassium concentrations. On the first post-operative day, the diclofenac group demonstrated a reduced urinary sodium excretion. On the second post-operative day, a reduced urinary NAG/creatinine ratio was observed in the diclofenac group when compared to placebo. We conclude that peri-operative administration of diclofenac causes changes in renal function consistent with prostaglandin inhibition on the first post-operative day but had no lasting adverse effects in this group of patients. Our results reinforce the need for caution when administering this drug in the context of pre-existing renal impairment.

Acetylglucosaminidase↗

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.

Alpha Rhythm↗

An electroretinogram protocol for toxicological screening in the canine model.

A five-step electroretinogram protocol was developed for the dog to be used as a painless screening test for ocular effects of drugs or pesticides. Standard conditions of frequency band width, stimulus intensity, dark adaptation time and non-confounding anesthesia method were selected to allow analysis of wave components. The protocol demonstrated an acceptable level of inter-subject variability for compiling an age appropriate database, and for the detection of possible retinal component toxicities in chronic dog studies. This electrophysiologic procedure may serve to corroborate biochemical, clinical and pathology data, in establishing a compound's no-observable-effect-level (NOEL).

Animals↗

A quantitative electroencephalographic method for xenobiotic screening in the canine model.

A method, using quantitative electroencephalography (qEEG), was developed for screening xenobiotics in conjunction with neurological examinations, for defining toxicodynamic profiles of certain drugs and chemicals in the dog. The standard 10-channel montage was used to evaluate normotonic, auditory, visual, and somatosensory cortical activity. Compressed spectral analysis and Fourier Transformation determined spectral edge frequencies, distribution of the total, fractional and absolute powers of delta, theta, alpha, and beta frequencies as parameters. The alpha 2-agonist, xylazine, was used to detect treatment-related differences, threshold effect levels, and qEEG-target parameters. An increase in theta and alpha activity, and a shift to lower spectral edge frequency were noted. Visual stimulation was the least sensitive test condition in detecting significant changes in measured parameters. Data derived by qEEG may make a reliable contribution to the physiologic interpretation, along with biochemical, clinical, and pathological data collected during a regulatory study.

Animals↗

Use of two oximeters to investigate a method of movement artefact rejection using photoplethysmographic signals.

Oxygen haemoglobin saturations and plethysmograph signal amplitudes were recorded from two oximeters placed on the fingers and toes of 10 patients undergoing oesophagectomy, to assess a method of removing motion artefact from saturation recordings. By examining changes in the plethysmograph amplitude that preceded changes in saturation, episodes of desaturation caused by movement artefacts were removed from the data. The reliability of the method was then determined by scrutinizing two concurrent oximetric profiles from each patient. A total of 1600 h of data were evaluated. Desaturations occurring contemporaneously in both oxygen saturation profiles were presumed genuine, whereas a desaturation occurring in only one of the profiles was classified as artefactual. Our method had a sensitivity of 96%, a positive predictive power of 98% and a specificity of 60%. We modified the method to increase specificity and re-evaluated our data. We found that a useful increase in specificity was associated with a considerable decline in sensitivity.

Aged↗

Bioavailability and pharmacokinetics of metoclopramide in cattle.

The bioavailability of metoclopramide was investigated in three steers following administration of 8 mg/kg by the oral, abomasal (cannula), and intravenous routes, using a Latin square design. The mean (+/- SD) oral and abomasal bioavailabilities were 51.3 +/- 30.7% and 76.2 +/- 15.5%, respectively. The mean value for clearance (Cl) was 20.1 +/- 5.9 ml/min and the volume of distribution (Vd) was 0.51 +/- 0.19 l/kg. Additional pharmacokinetic parameters for metoclopramide were determined following intravenous administration to seven cows. A predominate two-compartment model of distribution was found in six cows with a t 1/2 alpha harmonic mean of 24.2 min and a range of 11.2-72.4 min, a t 1/2 beta harmonic mean of 53.1 min and a range of 31.1-134.1 min, a Cl of 42.2 +/- 8.7 ml/min, and a Vd of 2.1 +/- 0.8 l/kg. To better define the relationship between metoclopramide concentration and release of prolactin, a treatment-by-subjects infusion study was conducted in which four different loading doses followed by constant infusion were used. A steady-state metoclopramide concentration (MCPss) of 8.8 +/- 2.6 ng/ml was associated with a three-fold elevation of prolactin to a mean value of 12.1 +/- 3.1 ng/ml in six yearling steers. Steady state serum prolactin concentrations (PRLss) did not rise significantly above 23.3 +/- 6.9 ng/ml, even when MCPss reached a concentration of 518.5 +/- 151.2 ng/ml. The short half-life, moderate Vd, low minimum pharmacologically effective concentration, and rapid Cl found for metoclopramide in cattle in this study, suggest that a continuous release device could potentially be useful in the application of this drug in the prevention and treatment of fescue toxicosis.

Abomasum↗

A central executive deficit in patients with Parkinson's disease.

Eight patients with Parkinson's disease and eight matched controls were tested for concurrent task performance to examine whether Parkinson's disease produces deficits in the coordinating and integrating function of the central executive component of Baddeley's working memory model. Consistent with this prediction, the patients showed a significant decline in performance on a random pursuit tracking task while recalling digit span forward sequences, whereas the controls showed no such change. Performance on the component pursuit and digit span tasks, which did not differ between groups, was equated across subjects by varying the size of a target square and by using individual subjects' digit spans. The patient group also produced poorer word fluency scores and reported higher levels of depression, but there was no significant impairment on the Wisconsin card sort test. There was no association between dual task performance and any psychometric measure, target size, or disease related variables. Baddeley's working memory model is advantageous in providing a rich conceptual basis to explore and characterise cognitive abilities in patients with Parkinson's disease.

Aged↗

Survey of antimony workers: mortality 1961-1992.

The mortality of a census population and a prospective cohort of men employed on an antimony smelter in the north east of England was followed up from 1961-1992. The workers studied were exposed to a variety of agents including antimony and its oxides, arsenic and arsenic oxides, sulphur dioxide, and polycyclic aromatic hydrocarbons. The regional mortality rates were used to calculate expected deaths and a group of zircon sand workers employed on the site were used as a comparison group. For the census population of men working on the smelter before 1961 a significant increase in deaths from lung cancer was found (32 observed v 14.7 expected, P < 0.001). A similar excess was seen among maintenance men (12 observed v 5.3 expected P = 0.016). No such excess was found in the cohort recruited after 1960 (5 observed v 9.2 expected, maintenance workers 3 observed v 2.8 expected). There was evidence of a minimum latency period of around 20 years between first exposure and death from lung cancer. No evidence was found for a correlation between length of time worked and mortality from lung cancer. The results show that an increased risk of lung cancer existed in the workers employed before 1961, but it was not possible to attribute this excess to any particular agent. Mortality analysed by five year calendar periods of first exposure show a lessening of effect after 1955. Although the power of the study is clearly less for more recent periods of exposure the absence of any excess in the population after 1960 is encouraging.

Adult↗

Preoperative and postoperative oxygen saturation in the elderly following spinal or general anaesthesia--an audit of current practice.

We have compared the incidence of preoperative and postoperative oxygen desaturation in 20 elderly patients undergoing dynamic hip screw insertion for fractured neck of femur, allocated randomly to two groups to receive subarachnoid anaesthesia (SA, n = 10) or a general anaesthetic (GA, n = 10). Oximetry data were recorded during the preoperative night and the first 48 hours after surgery using Satmaster. Data associated with zero amplitude signal were automatically invalidated by the software and decreases in SpO2 which were preceded by contemporaneous changes in signal amplitude which conformed to a previously described template were assumed to be artefactual and were discarded from final data analysis. Data demonstrated a wide interpatient variability. However, those patients who desaturated preoperatively continued to do so in the postoperative period. The differences between the preoperative and postoperative oximetry profiles were examined for each patient and demonstrated a significantly longer time spent with SpO2 < 90% in the GA group compared with the SA group, in all the recorded time periods, except on the day of surgery. The SA group showed an improvement in oxygen saturation postoperatively when compared to the preoperative night, spending less time with an SpO2 < 85%. We conclude that the subarachnoid anaesthetic technique was associated with a lower incidence of postoperative oximetry desaturation when compared with general anaesthetic for these elderly patients undergoing repair of fractured neck of femur.

Aged↗

Premedication with oral midazolam in children--an assessment of psychomotor function, anxiolysis, sedation and pharmacokinetics.

We studied 30 children, aged 4 to 12 years, undergoing elective circumcision, premedicated with midazolam 0.5 mg.kg-1 and atropine 0.02 mg.kg-1 by mouth. A modified postbox test and the coding component of the Wechsler intelligence scale (WISC-R) was used to assess the preoperative effect of premedication on psychomotor function. Mood and sedation were also scored and related to serum midazolam concentrations. The children showed a significant decline in psychomotor performance 30 and 60 minutes after premedication when compared with their best unmedicated performance recorded the previous evening. This decline in psychomotor performance was only weakly associated with serum midazolam concentrations (r = 0.1). The postbox toy ratio is a suitable measurement of psychomotor performance in children because of its simplicity and ease of use in the clinical environment, although it may suffer the "test-retest" limitations of similar types of assessment. The sedative and anxiolytic effects of midazolam provide a quiet environment for a smooth induction of anaesthesia.

Administration, Oral↗