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P G Wallace

Publications and source records attributed to P G Wallace.

At least 19 recordsLinked to original sources
PubMed1992

Operation and energy dependence of the reducing-equivalent shuttles during lactate metabolism by isolated hepatocytes.

The participation and energy dependence of the malate-aspartate shuttle in transporting reducing equivalents generated from cytoplasmic lactate oxidation was studied in isolated hepatocytes of fasted rats. Both lactate removal and glucose synthesis were inhibited by butylmalonate, aminooxyacetate or cycloserine confirming the involvement of malate and aspartate in the transfer of reducing equivalents from the cytoplasm to mitochondria. In the presence of ammonium ions the inhibition of lactate utilization by butylmalonate was considerably reduced, yet the transfer of reducing equivalents into the mitochondria was unaffected, indicating a substantially lesser role for butylmalonate-sensitive malate transport in reducing-equivalent transfer when ammonium ions were present. Ammonium ions had no stimulatory effect on uptake of sorbitol, a substrate whose oxidation principally involves the alpha-glycerophosphate shuttle. The role of cellular energy status (reflected in the mitochondrial membrane electrical potential (delta psi) and redox state), in lactate oxidation and operation of the malate-aspartate shuttle, was studied using a graded concentration range of valinomycin (0-100 nM). Lactate oxidation was strongly inhibited when delta psi fell from 130 to 105 mV whereas O2 consumption and pyruvate removal were only minimally affected over the valinomycin range, suggesting that the oxidation of lactate to pyruvate is an energy-dependent step of lactate metabolism. Our results confirm that the operation of the malate-aspartate shuttle is energy-dependent, driven by delta psi. In the presence of added ammonium ions the removal of lactate was much less impaired by valinomycin, suggesting an energy-independent utilization of lactate under these conditions. The oxidizing effect of ammonium ions on the mitochondrial matrix apparently alleviates the need for energy input for the transfer of reducing equivalents between the cytoplasm and mitochondria. It is concluded that, in the presence of ammonium ions, the transport of lactate hydrogen to the mitochondria is accomplished by malate transfer that is not linked to the electrogenic transport of glutamate across the inner membrane, and, hence, is clearly distinct from the butylmalonate-sensitive, energy-dependent, malate-aspartate shuttle.

Ammonia↗
PubMed1992

Preparation of the critically ill for interhospital transfer.

Changes in monitoring and therapy during the preparation of 100 critically ill patients for interhospital transfer by a specialist team were documented prospectively with the aim of providing guidelines for nonspecialists. Severity of illness scores were recorded before and after preparation. Median duration of preparation for ambulance journeys was 50 min and for aeroplane journeys was 82 min. During preparation, a portable electrocardiogram and pulse oximeter were attached to 21 and 76 patients respectively and intra-arterial pressure monitoring was continued or instituted in 88 patients. Supplemental oxygen and intravenous fluids were the therapies most commonly increased or instituted by the transport team; mechanical ventilation, positive end-expiratory pressure and inotropic drugs were increased or instituted less frequently. Median therapeutic intervention scores before and after preparation were 21 and 23 respectively, highlighting the need to increase rather than withdraw support for transfer.

Adolescent↗
PubMed1992

Helicopters.

Explore the source record for details and available documents.

Aircraft↗
PubMed1991

Post-viral fatigue syndrome. Epidemiology: a critical review.

Numerous reports in medical journals, lay magazines, and newspapers bear witness to the level of interest in the postviral fatigue syndrome and the heated controversy about the true nature of this condition. For many, it represents a 'rag bag' diagnosis into which unsolved diagnostic problems are discarded. Others are in no doubt that there is a discrete syndrome, probably with a specific causation. The real answer almost certainly lies somewhere in between, but the truth can only be established through epidemiological studies designed to answer key questions. Does it exist at all, and, if so, how frequently does it occur? Who is most likely to get it and what is its cause? What is the nature of its implied association with viral infections and what is the role of other frequently postulated factors, such as psychiatric morbidity? What is its natural history and is there any evidence that any of the treatment/management regimes on offer can effectively lead to symptomatic relief or improve prognosis? In this chapter, we consider the evidence on these key questions, identify some of the deficiencies in our current knowledge and highlight the kind of research which is still required.

Epidemiologic Methods↗
PubMed1990

Effective use of regional intensive therapy units.

OBJECTIVE: To determine the effectiveness of regional intensive therapy units. DESIGN: Retrospective and prospective study of patients transferred to a regional intensive therapy unit over four years. SETTING: Glasgow regional intensive therapy unit. MAIN OUTCOME MEASURES: Severity of illness was assessed at the time of referral to the unit with the acute physiological and chronic health evaluation (APACHE) scoring system. Mortality was calculated. RESULTS: A significant association was found between increasing duration of illness before transfer and mortality, which was independent of the severity of illness. Mortality also varied depending on the referring hospital. CONCLUSIONS: When transfer of critically ill patients is required this should be done as early as possible to make best use of the services available. The mortality of patients transferred after 10 days casts doubt on whether further aggressive intensive therapy is appropriate.

Hospitalization↗
PubMed1990

Current practice in transferring critically ill patients among hospitals in the west of Scotland.

OBJECTIVE: To identify the requirements of an interhospital transfer service for critically ill patients. DESIGN: Retrospective survey of the current functions of a specialist interhospital transfer team from data collected at the time of transfer and from records of intensive care unit. SETTING: Mobile intensive care unit based at a tertiary referral centre, which serves the west of Scotland. PATIENTS: All critically ill patients (378) transferred between hospitals by the unit from 1986 to 1988. RESULTS: 365 Patients were transferred by road and 13 by air. There was a wide variation in age (range 6 weeks to 87 years), diagnosis, reason for transfer, support required, and distance travelled. Most patients (232) were transferred for respiratory or cardiovascular support; 100 were trauma cases. 300 Patients (79%) were mechanically ventilated during transfer. No patient died in transit, although the eventual mortality was 28% (105 patients). Mortality was significantly higher in patients transferred from hospitals with intensive care units than from those without (38% (125 patients) v 23% (253); p less than 0.005). IMPLICATIONS: Safe interhospital transfer of critically ill patients is feasible; the high eventual mortality in some patient groups emphasises the need for accurate prediction of outcome if inappropriate transfer is to be avoided. The findings may help in organising secondary transfer services in future.

Adolescent↗
PubMed1990

Quality of life after intensive care.

An important aspect of effectiveness of intensive care services is change in the quality of life of survivors after critical illness. A questionnaire was complied using established methods for assessment of quality of life and sent to all known survivors of a regional intensive care unit. Each patient's quality of life was then quantified using disability categories. The results show that patients with a good premorbid quality of life suffered a significant decline after critical illness. Similar important decreases in quality of life were found in younger patients and trauma victims. Quality of life may be a valuable consideration in determining the appropriateness of intensive care management.

Activities of Daily Living↗
PubMed1989

Comparison of propofol and midazolam for sedation in critically ill patients.

101 critically ill patients admitted to five intensive-care units were allocated randomly to receive a continuous intravenous infusion of either propofol or midazolam for sedation for up to 24 h. In addition, morphine was given to provide analgesia. The mean duration of infusion was 20.2 h (range 3.0-24.5) in the propofol group and 21.3 h (4.0-47.0) in the midazolam group and infusion rates were 1.77 mg/kg/h (range 0.40-5.00) and 0.10 mg/kg/h (0.01-0.26), respectively. The infusion rates were adjusted as necessary, and the desired level of sedation was achieved easily in most patients in both groups. There were slight falls in arterial pressure, but there were no significant differences between the groups. Heart rate was lower in patients who received propofol. Some small changes occurred in biochemical and haematological variables in both groups, but they were not clinically significant. There was no indication that either drug substantially impaired adrenal steroidogenesis. When the infusion was discontinued, there was less variability in recovery of consciousness in patients who had received propofol. In a subgroup of patients, weaning from mechanical ventilation was achieved significantly faster after discontinuation of propofol than of midazolam. Propofol proved to be a satisfactory agent for sedation of these critically ill patients and compared favourably with midazolam.

Adolescent↗
PubMed1988

Intracellular mitochondrial membrane potential as an indicator of hepatocyte energy metabolism: further evidence for thermodynamic control of metabolism.

The lipophilic triphenylmethylphosphonium cation (TPMP+) has been employed to measure delta psi m, the electrical potential across the inner membrane of the mitochondria of intact hepatocytes. The present studies have examined the validity of this technique in hepatocytes exposed to graded concentrations of inhibitors of mitochondrial energy transduction. Under these conditions, TPMP+ uptake allows a reliable measure of delta psi m in intracellular mitochondria, provided that the ratio [TPMP+]i/[TPMP+]e is greater than 50:1 and that at the end of the incubation more than 80% of the hepatocytes exclude Trypan blue. Hepatocytes, staining with Trypan blue, incubated in the presence of Ca2+, do not concentrate TPMP+. The relationships between delta psi m and two other indicators of cellular energy state, delta GPc and Eh, or between delta psi m and J0, were examined in hepatocytes from fasted rats by titration with graded concentrations of inhibitors of mitochondrial energy transduction. Linear relationships were generally observed between delta psi m and delta GPc, Eh or J0 over the delta psi m range of 120-160 mV, except in the presence of carboxyatractyloside or oligomycin, where delta psi m remained constant. Both the magnitude and the direction of the slope of the observed relationships depended upon the nature of the inhibitor. Hepatocytes from fasted rats synthesized glucose from lactate or fructose, and urea from ammonia, at rates which were generally linear functions of the magnitude of delta psi m, except in the presence of oligomycin or carboxyatractyloside. Linear relationships were also observed between delta psi m and the rate of formation of lactate in cells incubated with fructose and in hepatocytes from fed rats. The linear property of these force-flow relationships is taken as evidence for the operation of thermodynamic regulatory mechanisms within hepatocytes.

Adenine Nucleotides↗
PubMed1988

Evidence that stimulation of gluconeogenesis by fatty acid is mediated through thermodynamic mechanisms.

We have studied the stimulatory effects of palmitate on the rate of glucose synthesis from lactate in isolated hepatocytes. Control of the metabolic flow was achieved by modulating the activity of enolase using graded concentrations of fluoride. Unexpectedly, palmitate stimulated gluconeogenesis even when enolase was rate-limiting. This stimulation was also observed when the activities of phosphoenolpyruvate carboxykinase and aspartate aminotransferase were modulated using graded concentrations of quinolinate and aminooxyacetate, respectively. Linear force-flow relationships were found between the rate of gluconeogenesis and indicators of cellular energy status (i.e. mitochondrial membrane and redox potentials and cellular phosphorylation potential). These findings suggest that the fatty acid stimulation of glucose synthesis is in part mediated through thermodynamic mechanisms.

Aminooxyacetic Acid↗
PubMed1988

Assessing alcohol consumption in general practice patients--a comparison between questionnaire and interview (findings of the Medical Research Council's general practice research framework study on lifestyle and health).

A self-administered questionnaire, the Health Survey Questionnaire (HSQ) was distributed to patients registered with 47 group general practices. The HSQ assesses alcohol consumption using a quantity frequency scale and includes the four CAGE questions and a question on whether respondents think they have an alcohol problem. A random stratified sample of those patients who returned an HSQ (2666 men and 1537 women) were subsequently invited to attend their general practice for an interview with the practice nurse, where weekly alcohol consumption was estimated using both a quantity frequency scale and a systematic enquiry about alcohol consumption for the week immediately preceding the interview. The latter method was taken as the 'gold standard'. Excessive drinkers were defined as men whose weekly consumption by this method was not less than 35 units per week and women drinking at least 21 units per week. After weighing the results to take account of the sampling bias in favour of the excessive drinkers, 11.7% of men and 2.9% of women were excessive drinkers according to the estimate of alcohol consumption at interview. This compares with the 7.6% of men and 2.7% of women who were heavy drinkers by the HSQ quantity frequency scale. The two interview estimates were comparable but in general the HSQ tended to underestimate consumption compared with these estimates. The questionnaire was found to be most effective in screening for excessive drinkers if all the patients who indicated concern about their drinking (i.e. those who were with CAGE positive or had a self-assessed drinking problem), as well as all of those who were above the limits for the trial on the quantity frequency scale, were selected as being potentially excessive drinkers. In the weighted sample, 14.8% of men and 6.9% of women were in this group. Using these selection criteria and taking the interview as the standard for determining the excessive drinkers a sensitivity of 58.6% and specificity of 91.08% was obtained for men, with a positive predictive value of 46.1% and a negative predictive value of 94.3%. For women the test was more sensitive (69.7%) and more specific (95.0%) and had a better negative predictive value (99.1%) than for men. The positive predictive value for women at 29.6% was not as good as that obtained for men. This analysis shows that the HSQ is a fairly effective tool for detecting excessive drinkers in general practices with a small proportion of false positive results. It is both economical and acceptable to patients in a wide range of practice settings.

Alcohol Drinking↗
PubMed1987

Linear relationships between mitochondrial forces and cytoplasmic flows argue for the organized energy-coupled nature of cellular metabolism.

We have studied rates of formation of glucose, urea and lactate by isolated hepatocytes incubated with a variety of inhibitors of energy transduction. Linear relationships have been found between these metabolic rates and mitochondrial forces (membrane, redox and phosphorylation potentials). The findings are suggestive of extensive enzyme organization within these metabolic pathways.

Animals↗
PubMed1987

Are general practitioners doing enough to promote healthy lifestyle? Findings of the Medical Research Council's general practice research framework study on lifestyle and health.

The health survey questionnaire was used to collect information about cigarette smoking, alcohol consumption, physical exercise, and dieting and weight. Completed questionnaires were received from 25,496 men and 36,657 women registered with 47 group practices in England and Scotland. The proportions of respondents who stated that they had a problem ranged from 1% (women and drinking, n = 406) to 34% (women and weight, n = 12,526). Between 49% (women and drinking, n = 18,048) and 67% (men (n = 17,095) and women (n = 24,550) and weight) thought that their general practitioners should be interested in their lifestyle. The proportions who could recall having received relevant advice ranged from 2% (women and drinking, n = 591) to 24% (women and weight, n = 8946). Advice about smoking had been given to 4055 (40%) of the women and 2941 (39%) of the men who smoked. Only 96 (10%) of the 989 women and 331 (17%) of the 1948 men who drank excessively could recall having received advice about alcohol consumption. These results suggest that patients are concerned about their lifestyle, that most would welcome relevant counselling, and that doctors should become more concerned with prevention of this kind.

Alcohol Drinking↗
PubMed1987

Propofol infusion for sedation in intensive care.

Ten patients, with a range of illness severity, received a continuous 8-hour infusion of undiluted propofol for sedation while undergoing mechanical ventilation in a general intensive care unit. The level of sedation was assessed hourly and measurements were made of haemodynamic, respiratory, haematological and biochemical variables. Sedation remained satisfactory in most patients throughout the study period, with only occasional alterations in infusion rate, and eight patients required further sedative therapy within 45 minutes of discontinuation of the propofol infusion. Arterial pressure tended to decrease from baseline values; mean and diastolic pressures demonstrated a significant decrease (p less than 0.05) at 4, 7 and 8 hours during the infusion. Adrenal steroidogenesis was not inhibited significantly. Propofol infusion proved to be a useful and readily controllable sedative agent, and discontinuation of the drug was followed by rapid recovery in most cases. The critically ill may be particularly sensitive to the cardiovascular depressant properties of the drug.

Aged↗
PubMed1987

Effects of thyroid state on respiration of perfused rat and guinea pig hearts.

The effects of thyroid state on the respiration of the isolated heart were investigated using retrograde perfused rat and guinea pig hearts. In both species, hypothyroidism caused a marked depression in circulating thyroid hormone concentrations and in the respiration of the isolated, retrograde perfused heart. The effects on myocardial respiration could be attributed to changes in the contraction frequency and in the oxygen consumption per beat, with little contribution from basal respiration. Treatment of animals with thyroxine elevated plasma thyroid hormones to a similar extent in rats and guinea pigs. In the latter, thyroxine treatment was associated with substantial increases in the contraction frequency and the oxygen consumption per beat of the isolated heart. In contrast, only small changes were apparent in the retrograde perfused rat heart, observations that were confirmed in rat hearts perfused at near physiological work loads. It was concluded that rat hearts isolated from normal animals function at near maximal thyroid state, in contrast to the guinea pig heart, which requires higher circulating concentrations of thyroid hormones to attain maximal responses.

Animals↗