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Biomedical subjects

J W Ward

Publications and source records attributed to J W Ward.

At least 127 records · Page 7Linked to original sources

Plasma concentrations of lignocaine and its metabolites during fibreoptic bronchoscopy.

Lignocaine metabolites are known to have both antiarrhythmic and toxic effects. Large plasma concentrations of these metabolites have been reported following endotracheal instillation of lignocaine. We measured plasma lignocaine monoethylglycinexylidide (MEGX), and glycinexylidide (GX) concentrations for up to 4h after fibreoptic bronchoscopy. The total dose of lignocaine required to suppress coughing varied between 230 mg and 364 mg. Small therapeutic lignocaine concentrations occurred transiently in nine of 19 patients after the bronchoscopy examination had finished. Only one patient achieved a plasma lignocaine concentration in the range of minor toxicity. Metabolite peaks occurred later and were of much smaller magnitude. They were unlikely to contribute to prophylaxis of cardiac arrhythmia or to toxicity. It would seem to be safe to use topical lignocaine in doses greater than the currently recommended maximum (200 mg) in conscious patients during fibreoptic bronchoscopy.

Aged↗

Fatty acid composition of phosphatidylinositol and phosphatidic acid in stimulated platelets. Persistence of arachidonyl-stearyl structure.

The fatty acid composition of phosphatidylinositol (PI), phosphatidic acid (PA), and the free fatty acid pool of human platelets was studied as a function of time following thrombin stimulation. Upon addition of thrombin, the total amount of fatty acids in PI decreased sharply, then rose toward basal levels, while that of PA showed an inverse pattern. However, the percentage distribution of fatty acids in stimulated as well as unstimulated PI and those in stimulated PA remained relatively constant: stearic and arachidonic acids accounted for 90 and 80% of the total in PI and PA, respectively. These data suggest that in stimulated human platelets PI and PA are interconverted via the "PI cycle." The time course of changes in PI and PA may suggest that the levels of arachidonyl-stearyl PA are involved in regulation of the resynthesis of arachidonyl-steryl PI. In contrast to PI and PA, the free fatty acid pool showed sharp increases in the five major platelet fatty acids: arachidonate, stearate, palmitate, oleate, as well as linoleate. These data suggest that most of the fatty acids liberated upon platelet stimulation are not derived via PI metabolism but by other mechanisms.

Arachidonic Acid↗

Evaluation of a syntactic pattern recognition approach to quantitative electroencephalographic analysis.

This paper reports an experiment designed to evaluate the usefulness of a syntactic pattern recognition approach to quantitative EEG analysis. This approach provides a systematic way of organizing and interpreting spatially and temporally distributed activity in an EEG record. Many automated scoring systems evaluate only background activity, ignoring the significant transient events that may occur in an EEG. In contrast, syntactic methods allow evaluation of background activity in combination with transient events. In this paper, 454 EEGs recorded from a population of renal patients are evaluated using (1) the syntactic approach, and (2) a method based on discriminant analysis. The main finding is that the syntactic approach outperforms the discriminant analysis method when each technique is compared to visual scoring.

Electroencephalography↗

Compliance with the new Food and Drug Administration regulations: an approach by industry.

Good Laboratory Practice regulations became effective on June 20, 1979. The regulations provide guidance for the proper conduct and reporting of nonclinical laboratory studies on articles regulated by the United States Food and Drug Administration. A fundamental requirement of the regulations is the establishment of a quality assurance unit within each research facility to ensure the utilization and maintenance of good laboratory practices. A second significant feature is the requirement for an archival unit responsible for maintaining all raw data, documentation, protocols, specimens, and final reports. Experience with the regulations has been mixed. The quality of reports has been upgraded dramatically. Protocols contain more information than ever, data recording is more extensive and more carefully executed, and reports are prepared more carefully and edited more thoroughly. Conversely, there is no real evidence that quality of science has been improved, and costs have increased markedly.

Dairying↗

Assessing the adequacy of dialysis.

In previous work, probes of brain function (quantified EEG and cognitive performance) objectively measured clinical differences patients with chronic renal failure before and after treatment with maintenance haemodialysis or transplantation. This study applied those measures (EEG-discriminant score; choice reaction time, CRT; continuous memory test, CMT; clinical-symptom/self-evaluation questionnaire, CSE) in a prospective experiment to determine whether our standard amount (time) of thrice weekly dialysis could be reduced without inducing some degree of clinical uraemia. In 10 patients a 6 month experimental (E) period was preceded by a 3 month control (CI) and followed by a 3--6 month control (C2) period. During E dialysis time was reduced so that residual renal (Kr) plus dialyser (Kd) urea clearance per week per litre of patients' body water approximated 50--80 percent of the control-level of 3000ml/wk/L. In response average values of all measures worsened; EEG, 54 percent; CRT, 2.5 percent; CMT, 21 percent; and CSE, 11 percent. BUN levels rose slightly, urea generation rates fell, and patients insisted that they felt better as they recorded more severe symptoms (CSE). We conclude: (i) that Kr + Kd = 3000ml/wk/L approximates a minimum level of adequate dialysis; (ii) objective measures which index the neurobehavioural syndrome of clinical uraemia detect inadequate (reduced) dialysis.

Adult↗

A software system for syntactic analysis of the EEG.

This paper describes an interlocking set of programs used for syntactic analysis of the electroencephalogram. This system constitutes a basic set of programs in the Vanderbilt EEG analysis system (VEAS). The concepts underlying the methods are explained and examples of the use of the system are given. The algorithms employed for spatial, temporal and global parsing of 'EEG sentences' are presented and examples of the use of various grammatical rules are described.

Computers↗

Disopyramide and lignocaine. A comparison of cardiac effects using echocardiography.

1 The cardiac effects of disopyramide (D) and lignocaine (L) were measured and compared in normal volunteers (D n=4; L n=3) following the establishment of a series of three steady-state drug plasma concentrations spanning the therapeutic range (1.5-5 micrograms base ml-1). 2 During control and steady-state periods multiple measurements were made of heart rate, blood pressure, drug concentrations and echocardiographic measurement of cardiac dimensions and estimated left ventricular function. 3 No change in heart size or estimated function occurred with L except for a small increase in estimated cardiac output (+0.5 1 min-1) secondary to a small rise in heart rate (maximum +7 beats min-1). Blood pressure rose slightly (maximum +11 mmHg). 4 D caused an increase in heart size, marked at end systole (+0.63 cm), and a decrease in echo indices of ventricular function (25-33%). These changes were related to plasma drug concentration but were not reflected in cardiac output estimation since heart rate rose (+15 beats min-1). Blood pressure also rose (+10 mmHg). 5 Significant differences were shown between D and L at similar plasma drug concentrations. The negative inotropic effect of D may be greater than previously suggested and clinically important.

Adult↗

The use of choline chloride in ataxic disorders.

Fourteen patients with a variety of ataxic disorders were given choline chloride, double blind for six weeks, in an attempt to improve gait and manual dexterity. One patient withdrew before receiving the active drug, twelve patients showed no functional improvement, but one achieved greater mobility; his response, which was dose dependent, ceased when choline was stopped and was reproducible.

Adult↗

Phospholipid metabolism in stimulated human platelets. Changes in phosphatidylinositol, phosphatidic acid, and lysophospholipids.

Endogenous phospholipid metabolism in stimulated human platelets was studied by phosphorus assay of major and minor components following separation by two-dimensional thin-layer chromatography. This procedure obviated the use of radioactive labels. Extensive changes were found in quantities of phosphatidylinositol (PI) and phosphatidic acid (PA) as a consequence of thrombin or collagen stimulation. Thrombin addition was followed by rapid alterations in the amount of endogenous PI and PA. The decrease in PI was not precisely reciprocated by an increase in PA when thrombin was the stimulus. This apparent discrepancy could be explained by removal of a transient intermediate in PI metabolism, such as diglyceride, formed by PI-specific phospholipase C (Rittenhouse-Simmons, S., J. Clin. Invest.63: 580-587, 1979). Diglyceride would be unavailable for PA formation by diglyceride kinase, if hydrolyzed by diglyceride lipase (Bell, R. L., D. A. Kennerly, N. Stanford, and P. W. Majerus. Proc. Natl. Acad. Sci. U. S. A.76: 3238-3241, 1979) to yield arachidonate for prostaglandin endoperoxide formation. Thrombin-treated platelets also accumulated lysophospho-glycerides. Specifically, lysophosphatidyl ethanolamines accumulated within 15s following thrombin addition. Fatty acid and aldehyde analysis indicated phospholipase A(2) activity, with an apparent preference for diacyl ethanolamine phosphoglycerides. In the case of collagen, these changes occurred concomitantly with aggregation and consumption of oxygen for prostaglandin endoperoxide formation.THESE STUDIES OF ENDOGENOUS PHOSPHOLIPID METABOLISM PROVIDE INFORMATION SUPPORTING THE EXISTENCE OF TWO PREVIOUSLY POSTULATED PATHWAYS FOR LIBERATION OF ARACHIDONIC ACID FROM PLATELET PHOSPHOLIPIDS: (a) the combined action of PI-specific phospholipase C plus diglyceride lipase yielding arachidonate derived from PI; and (b) a phospholipase A(2) acting primarily on diacyl ethanolamine phosphoglyceride.

Arachidonic Acids↗

Quantitative indices of clinical uremia.

The disabling, dialysis-responsive symptoms of clinical uremia primarily represent impaired functions of the nervous system. Accordingly, these studies used several quantitative electrophysiologic and cognition-dependent probes of nervous system function: peripheral nerve-conduction velocity, response latency and amplitude; electroencephalographic (EEG) power-spectrum analysis; visual evoked response latency; EEG responses to photic driving; and measures of integrated behavioral performance that stressed sustained and selective attention, reaction time, speed of decision-making, short-term memory, and mental manipulation of symbols. Probes of quanitified central nervous system function consistently revealed impairments that varied directly with the degree of renal failure, that improved following onset of maintenance dialysis, and that improved still further after successful renal transplantation. In contrast, measures of peripheral nerve function were generally unchanged. Neurobehavioral measures that are relevant to uremic symptomatology provide quantitative estimates of the clinically significant, whole-organism biologic effects of renal failure and its several treatments. Applications of such measures in studies of symptomatic states other than uremia are indicated also.

Adolescent↗

Visually evoked cortical potentials in renal failure: transient potentials.

Transient visually evoked cortical potentials (VECPs) were recorded from patients with renal disease. Changes in VECP latencies are described for undialyzed patients, patients receiving dialysis therapy, and patients who received kidney transplants. Characteristics of VECP latencies in these patient groups as well as examples of changes in latency values with respect to time for two individual patients are examined. The basic overall finding is that the VECP latencies increase as a patient's clinical condition deteriorates and normalize as the condition improves.

Adolescent↗

Quantitative assessment of photic driving in renal failure.

Photically driven EEGs were recorded from patients with renal disease using photic stimulation at integer rates between 3 and 12 flashes/sec. Changes in the structure of the power spectrum of the potentials produced by this stimulus paradigm are described as a function of a patient's clinical state. The basic overall findings are that (1) harmonic activity is attenuated while activity below the fundamental driving frequency is increased as a patient's clinical condition deteriorates, and (2) that these effects are substantially reversed and controlled by means of dialysis and renal transplantation.

Adolescent↗