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J G Jones

Publications and source records attributed to J G Jones.

At least 73 records · Page 4Linked to original sources
PubMed1997

Measurement of gluconeogenesis and pyruvate recycling in the rat liver: a simple analysis of glucose and glutamate isotopomers during metabolism of [1,2,3-(13)C3]propionate.

Simple equations that relate glucose and glutamate 13C-NMR multiplet areas to gluconeogenesis and pyruvate recycling during metabolism of [1,2,3-(13)C3]propionate are presented. In isolated rat livers, gluconeogenic flux was 1.2 times TCA cycle flux and about 40% of the oxaloacetate pool underwent recycling to pyruvate prior to formation of glucose. The 13C spectra of glucose collected from rats after gastric versus intravenous administration of [1,2,3-(13)C3]propionate indicated that pyruvate recycling was slightly higher in vivo (49%) while glucose production was unchanged. This indicates that a direct measure of gluconeogenesis and pyruvate recycling may be obtained from a single 13C-NMR spectrum of blood collected after oral administration of enriched propionate.

Animals↗
PubMed1997

Determination of acetyl-CoA enrichment in rat heart and skeletal muscle by 1H nuclear magnetic resonance analysis of glutamate in tissue extracts.

The contribution of a 13C-enriched substrate to the acetyl-CoA pool in animal tissues is typically measured by analysis of glutamate enrichment from tissue extracts. 13C NMR analysis offers the advantages of minimal sample processing and high information content, but has a low analytical sensitivity compared to other methods of tracer analysis such as GC/MS. We present a sensitive, simple, and direct 1H NMR measurement of glutamate C4 enrichment from tissue extracts. The method is demonstrated with heart and hindlimb muscle tissue extracts of rats infused with [2,4,6,8-13C4]-octanoate, a source of [2-13C]acetyl-CoA. Glutamate C4 enrichment in extracts of individual hindlimb soleus muscles weighing approximately 150 mg and containing approximately 0.3 mumol of glutamate was quantified by 1H NMR within about 40 min. Glutamate C4 enrichment measurements by 1H NMR in heart and gastrocnemius muscle were also highly correlated with independent measurements obtained from 13C NMR isotopomer analysis.

Acetyl Coenzyme A↗
PubMed1997

Propofol neuroprotection in a rat model of ischaemia reperfusion injury.

This study was designed to test the hypothesis that propofol, which possesses antioxidant properties, would produce greater protection than isoflurane in cerebral ischaemia reperfusion injury, at dose levels that produced similar affects on brain electrical activity. Twenty Sprague-Dawley rats were anaesthetized using isoflurane 1.5% in air/oxygen, and mechanically ventilated to a PaCO2 of 4.5 kPa. Following 90 min of middle cerebral artery occlusion using an intraluminal filament, rats were given, in random order, either propofol 1 mg kg-1 min-1 or isoflurane 3% (both of which have been shown to reliably produce EEG burst suppression). After a further 30 min, reperfusion was induced by withdrawing the filament. Animals were killed following 240 min of reperfusion. Rats in the propofol group showed a 21% reduction in mean hemispheric infarct volume when compared with the isoflurane group (P < 0.0001). These data suggest that propofol may act by mechanisms in addition to CMRO2 depression, and provide a basis for further studies of propofol neuroprotection.

Anesthesia↗
PubMed1997

Intra-operative gas exchange and post-operative hypoxaemia.

The relation between intra-operative gas exchange and post-operative oxygen saturation was examined using pulse oximetry (SpO2) 30 h after anaesthesia for upper abdominal surgery. The inspired oxygen partial pressure (PIO2) was varied during anaesthesia to produce a plot of PIO2 vs. SpO2. Gas exchange during anaesthesia was inferred from the relation between PIO2 and SpO2 which was described by its lateral and vertical displacement away from the position of a standard oxygen dissociation curve. With patients breathing air, the SpO2 was measured over a 10-min period at 30 h after surgery. The correlation coefficient of the lateral displacement with post-operative SpO2 was 0.7, and that of the vertical displacement with post-operative SpO2 was 0.66. The correlation coefficient of intra-operative SpO2 at PIO2 = 21 kPa with post-operative SpO2 was 0.69. It can be concluded that gas exchange abnormalities during anaesthesia deduced from the displacement of the PIO2 vs. SpO2 curve correlate with SpO2 30 h post-operatively and may help to identify patients at risk of post-operative hypoxaemia.

Abdomen↗
PubMed1997

Non-invasive measurement of cerebral blood volume in volunteers.

Invasive techniques are used for conventional measurements of cerebral blood volume and there is a need for methods which are more readily applicable clinically. We studied 13 healthy volunteers using near infrared spectroscopy and transcranial Doppler sonography. Middle cerebral artery flow velocity (vmca) and changes in cerebral oxygenated haemoglobin (HbO2), deoxygenated Hb (Hb), HbO2 - Hb (Hbdiff) [corrected] and HbO2 + Hb (total haemoglobin; Hbt) were measured at baseline and during graded reduction in arterial oxygen saturation (Spo2) to 85% at hypo-, normo- and hypercapnia. Cerebral blood volume (CBV) values, calculated from regression lines of Hbdiff/SpO2 and HbO2/SpO2 were 5.38 and 4.03 ml 100 g-1 for the two methods, respectively. CBV varied directly with FE'CO2, with mean CBV reactivities of 1.25 and 1.06 ml 100 g-1 kPa-1, respectively. Changes in Hbt were not systematically related to changes in FE'CO2. An increase in vmca and reciprocal decrease in estimated cerebrovascular resistance were observed when oxygen saturation decreased to less than 90-93%. These results suggest that cerebral haemodynamics in individual subjects may be monitored non-invasively providing the methodology is modified to account for hypoxic vasodilatation.

Adult↗
PubMed1997

Responses to simulated anaesthetic emergencies by anaesthetists with different durations of clinical experience.

We have compared the responses of four groups of anaesthetists, with different durations of clinical experience, to nine different simulated emergencies. Five anaesthetists in each group completed each of the nine simulated emergencies. Anaesthetists with less than 1 yr experience performed less well than the three other groups of anaesthetists (chi-square, P < 0.02). However, all groups made serious errors in both diagnosis and treatment, and accepted treatment guidelines were not followed. We have shown that a simple, inexpensive simulator can be used to evaluate the performance of anaesthetists of different durations of clinical experience.

Anesthesiology↗
PubMed1997

Inaccurate reporting of simulated critical anaesthetic incidents.

Eleven anaesthetists completed a simulated anaesthetic which was deliberately complicated by a slow progressive bradycardia followed by an episode of severe bronchospasm. After the simulation, each anaesthetist was asked to complete an anaesthetic chart and a critical incident report. Considerable discrepancies were found between the anaesthetists' written accounts, a videotape of their performance and actual data from the simulator. During the simulations, all of the anaesthetists reacted appropriately and treated their "patient" successfully but their written accounts showed a tendency to record "typical" rather than actual events and to ignore events not consistent with their final diagnosis. Only four anaesthetists mentioned bradycardia in their written description and none accurately described the changes in arterial pressure during the episode of bronchospasm. The findings are in keeping with other studies which suggest that people record events as "schemata" rather than as collections of discrete facts. These results have significant implications for those involved in the teaching of anaesthesia and in the analysis of critical incidents.

Anesthesiology↗
PubMed1997

Clinical and toxicological findings in two young siblings and autopsy findings in one sibling with multiple hospital admissions resulting in death. Evidence suggesting Munchausen syndrome by proxy.

A 15-month-old girl underwent several emergency department (ED) visits and two admissions for parent-reported histories of ingestions, apnea, and seizures. She was initially admitted following reports of several unusual episodes of syncope accompanied by convulsive movements and was discharged on mephobarbital with a diagnosis of atypical seizure disorder. The day after discharge, she was brought to the ED in cardiopulmonary arrest and was resuscitated after a prolonged period. She was declared brain dead 2 days later. Ante- and postmortem toxicology produced several inconclusive findings, none of which explained death. Autopsy findings, including neuropathology, failed to demonstrate any significant disease processes. Approximately 3 months later, a 4-month-old female sibling was brought to the ED with a parent-reported history of apnea and seizures similar to the deceased child. A stool specimen obtained 2 days after admission contained numerous tiny seeds, which were found by gas chromatography-mass spectrometry analysis to contain lorazepam and temazepam. The role of these benzodiazepines in the apnea episodes in this infant was unknown, but the presence of the seeds in such a young infant coupled with the parent's aberrant behavior, led to the tentative diagnosis of Munchausen syndrome by proxy. This diagnosis was strengthened when results from these studies persuaded legal authorities to remove the surviving sibling from the parents, resulting in an asymptomatic recovery.

Anti-Anxiety Agents↗
PubMed1997

Thresholds for hypoxic cerebral vasodilation in volunteers.

UNLABELLED: The effects of hypoxemia on the cerebral vasculature have been described in animal models, but data from human studies are limited and have often relied on invasive methodology. The ability to detect a threshold for hypoxic vasodilatation in humans may be clinically useful, particularly in patients with impaired intracranial compliance. Because physiology may differ among subjects, it would be advantageous to measure such thresholds using noninvasive bedside techniques that could be readily applied to individual patients. We have attempted to identify thresholds of hypoxic vasodilatation in volunteers using noninvasive methods of measurement. Thirteen healthy volunteers were studied using transcranial Doppler sonography. Time-averaged middle cerebral artery maximal flow velocity (MCA FVx), mean arterial blood pressure, peripheral oxygen saturation (Spo2), and partial pressure of endtidal CO2 were measured at baseline and during graded reduction in arterial Spo2 to 85%, at normocapnia. Flow velocity and estimated cerebrovascular resistance (CVRe) were indexed and plotted against Spo2. There was no significant change in mean arterial pressure during desaturation to 85%, although the mean heart rate increased from 65 to 82 bpm. An increase in MCA FVx and reciprocal decrease in CVRe were observed when Spo2 decreased to below 90%. These results suggest that hypoxemic cerebral vasodilatation may be measured noninvasively and that in normal human volunteers, the threshold is at an Spo2 of 90%, which is greater than that previously reported. IMPLICATIONS: The ability to detect the point at which cerebral blood vessels dilate using noninvasive techniques is clinically advantageous. We have attempted to do this using transcranial Doppler sonography in volunteers whose inspired oxygen concentrations were gradually decreased. Thresholds of cerebral vasodilatation were found to be higher than those previously reported. These thresholds are important with regard to adequate perfusion in various pathologic states.

Adult↗
PubMed1997

Patients' memories of events during general anaesthesia.

Awareness remains a serious complication of general anaesthesia with potential adverse psychological sequelae. Even during seemingly adequate general anaesthesia, implicit memory may be retained along with the ability to subconsciously process auditory stimuli. As a result behaviour may be modified and postoperative progress influenced. We shall discuss the structure of memory and the effects of increasing doses of general anaesthesia on cognitive processes. In addition methods of assessing the depth of anaesthesia will be reviewed.

Anesthesia, General↗
PubMed1997

A noninvasive method for evaluating the effect of thoracotomy on shunt and ventilation perfusion inequality.

A new noninvasive method was used to evaluate gas exchange in 12 patients undergoing thoracotomy for a variety of surgical procedures. A plot of inspired oxygen partial pressure versus oxygen saturation was analysed to calculate the independent contribution of shunt and intermediate ventilation/perfusion ratio which occurs during general anaesthesia for thoracotomy. A model based on the inspired to arterial oxygen difference involving the shunt equation was used to show how the relationship between inspired oxygen partial pressure and oxygen saturation could be used to derive two parameters of oxygen exchange, the virtual shunt and an index of low ventilation/perfusion ratio. In all cases, there was a very good fit of the data to the model. Thoracotomy caused a mean increase in shunt from 13.8% to 20.8% and a worsening ventilation/perfusion ratio from 0.5 to 0.2, the magnitude of which depended on the underlying pathology. In two patients, the ventilation/perfusion ratio decreased to less than 0.1. The method enables the prediction of oxygen saturation at different inspired oxygen partial pressures and allows the two components of gas exchange to be isolated using simple routine measurements of inspired oxygen and pulse oximetry.

Anesthesia, General↗
PubMed1997

The need for basic sciences in the understanding and practice of anaesthesia.

We conducted a survey using an unstructured, then a structured, questionnaire to determine the attitudes of 78 postfellowship anaesthetists to the Basic Sciences component of the part I examination for the FRCA. Seventy-two per cent replied. These anaesthetists felt that about 65% of the basic science syllabus was essential to the understanding and practice of everyday anaesthesia, but there was varying opinion as to the importance of specific topics. Cardiovascular, respiratory, central nervous system and renal physiology were all regarded as essential, as was the pharmacology of anaesthetic drugs. Topics regarded as irrelevant included biochemistry, endocrinology, membrane theory and immunology. Paradoxically, there were many topics which anaesthetists regarded as essential but on which they were unable to give a tutorial. There was little difference between the responses of consultants and trainees. This survey may help to identify a core syllabus on which the majority of anaesthetists agree but also suggests that the current syllabus is overloaded with detail that has no place in clinical practice.

Anesthesiology↗
PubMed1997

Ecophysiological Evidence that Achromatium oxaliferum Is Responsible for the Oxidation of Reduced Sulfur Species to Sulfate in a Freshwater Sediment.

Achromatium oxaliferum is a large, morphologically conspicuous, sediment-dwelling bacterium. The organism has yet to be cultured in the laboratory, and very little is known about its physiology. The presence of intracellular inclusions of calcite and sulfur have given rise to speculation that the bacterium is involved in the carbon and sulfur cycles in the sediments where it is found. Depth profiles of oxygen concentration and A. oxaliferum cell numbers in a freshwater sediment revealed that the A. oxaliferum population spanned the oxic-anoxic boundary in the top 3 to 4 cm of sediments. Some of the A. oxaliferum cells resided at depths where no oxygen was detectable, suggesting that these cells may be capable of anaerobic metabolism. The distributions of solid-phase and dissolved inorganic sulfur species in the sediment revealed that A. oxaliferum was most abundant where sulfur cycling was most intense. The sediment was characterized by low concentrations of free sulfide. However, a comparison of sulfate reduction rates in sediment cores incubated with either oxic or anoxic overlying water indicated that the oxidative and reductive components of the sulfur cycle were tightly coupled in the A. oxaliferum-bearing sediment. A positive correlation between pore water sulfate concentration and A. oxaliferum numbers was observed in field data collected over an 18-month period, suggesting a possible link between A. oxaliferum numbers and the oxidation of reduced sulfur species to sulfate. The field data were supported by laboratory incubation experiments in which sodium molybdate-treated sediment cores were augmented with highly purified suspensions of A. oxaliferum cells. Under oxic conditions, rates of sulfate production in the presence of sodium molybdate were found to correlate strongly with the number of cells added to sediment cores, providing further evidence for a role for A. oxaliferum in the oxidation of reduced sulfur.

Journal Article↗
PubMed1997

Oxidation of lactate and acetate in rat skeletal muscle: analysis by 13C-nuclear magnetic resonance spectroscopy.

The balance between carbohydrate and fatty acid utilization in skeletal muscle previously has been studied in vivo by using a variety of methods such as arteriovenous concentration differences and radioactive isotope tracer techniques. However, these methodologies provide only indirect estimates of substrate oxidation. We used 13C-nuclear magnetic resonance (NMR) spectroscopy and non-steady-state isotopomer analysis to directly quantify the relative oxidation of two competing exogenous substrates in rat skeletal muscles. We infused [1,2-13C]acetate and [3-13C]lactate intravenously in anesthetized rats during the final 30 min of 35 (n = 10) or 95 (n = 10) min of intense, unilateral, rhythmic hindlimb contractions. 13C-NMR spectroscopy and isotopomer analysis were performed on extracts of gastrocnemius and soleus muscles from both the contracting and contralateral resting hindlimbs. We found that 1) [13C]lactate and [13C]acetate were taken up and oxidized by both resting and contracting skeletal muscles; and 2) high-intensity muscle contractions altered the pattern of substrate utilization such that the relative oxidation of acetate decreased while that of lactate remained unchanged or increased. Based on these findings, we propose that 13C-NMR spectroscopy in combination with isotopomer analysis can be used to study the general dynamics of substrate competition between carbohydrates and fats in rat skeletal muscle.

Acetates↗
PubMed1996

Contribution of various substrates to total citric acid cycle flux and anaplerosis as determined by 13C isotopomer analysis and O2 consumption in the heart.

A simple relationship between parameters derived from a 13C NMR isotopomer analysis and O2 consumption is presented that allows measurement of the absolute rate of acetyl-CoA oxidation and anaplerotic flux in tissues oxidizing a mixture of four substrates. The method was first applied in a study of the effects of work state and beta-adrenergic stimulation on net acetate oxidation and anaplerosis in the isolated working rat heart. The results demonstrate that the anticipated ratio of 2 between O2 consumption and TCA cycle flux for hearts oxidizing only acetate holds at low workload when anaplerosis is low, but deviates toward a factor of 3 under high workload conditions when anaplerosis is increased. This analysis was also extended to hearts that oxidize a more physiological mixture of substrates including long-chain fatty acids, acetoacetate, lactate, pyruvate, and glucose. We show that the contribution each substrate makes to total TCA cycle flux can be determined by combined 13C NMR and O2 consumption measurements. The present study also demonstrates that stimulation of anaplerosis (by addition of propionate) can significantly alter the relative contribution each substrate makes to total TCA cycle flux. We conclude if 13C labeling patterns are selected appropriately, a comprehensive picture of flux through all major metabolic pathways feeding the cycle can be determined in a single experiment even when complex physiological mixtures of substrates are provided.

Acetates↗
PubMed1996

Effects of different oxidative insults on intermediary metabolism in isolated perfused rat hearts.

13C and 31P NMR were used to evaluate exogenous substrate utilization and endogenous phosphate metabolites in perfused rat hearts exposed to tert-butylhydroperoxide (tert-BOOH) and hydrogen peroxide (H2O2). Both reagents caused a reduction in developed pressure compared to controls and, in agreement with previous 31P NMR data, had different effects on intracellular high-energy phosphates and glycolysis. 13C Isotopomer analysis of tissue extracts showed that H2O2 and tert-BOOH also had significantly different effects on substrate utilization by the citric acid cycle. The contribution of exogenous lactate and glucose to acetyl-CoA was 43% in controls and increased to over 80% in the presence of either oxidant. With tert-BOOH, exogenous glucose and lactate were both significant contributors to acetyl-CoA (44 +/- 2 and 41 +/- 3%). However, with H2O2, exogenous lactate supplied a much higher fraction of acetyl-CoA (72 +/- 2%) than glucose (9 +/- 1%). Also, when [2-(13)C] glucose was supplied, accumulation of [2-(13)C] and [5-(13)C] fructose 1,6-bisphosphate was observed in the presence of H2O2, indicating inhibition of glyceraldehyde-3-phosphate dehydrogenase. These results indicate that despite this glycolytic inhibition, H2O2 increased the utilization of pyruvate precursors when lactate was present as an alternative carbohydrate substrate.

Animals↗