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Biomedical subjects

C J French

Publications and source records attributed to C J French.

9 recordsLinked to original sources

Cryoprecipitate for the correction of coagulopathy associated with liver disease.

In patients with liver disease at risk of pulmonary oedema, cryoprecipitate (small volume) might be a viable alternative to fresh frozen plasma (FFP, large volume) in the correction of coagulopathy. However, the efficacy of cryoprecipitate in these patients has not been tested. We evaluated the role of cryoprecipitate in the correction of the coagulopathy of liver disease. To establish initial evidence of efficacy, six consecutive patients with hepatic failure and coagulopathy received five units of cryoprecipitate. Then, using a crossover design, 11 consecutive patients were randomized to receive either four units of FFP or five units of cryoprecipitate. Pre and post infusion International Normalized Ratio (INR), activated Partial Thromboplastin Time (aPTT), fibrinogen D-dimers, Factors V and IX, and reptilase time were measured. In the first six patients, cryoprecipitate improved the INR, aPTT and fibrinogen concentration (P = 0.03). In the crossover study, FFP administration produced a greater improvement in INR (P = 0.007) and aPTT (P = 0.005) than cryoprecipitate. However, there were no differences in any of the other measured variables. One patient developed acute pulmonary oedema while receiving FFP. Cryoprecipitate improves the coagulopathy of liver disease. Four units of FFP are more efficacious than five units of cryoprecipitate. Cryoprecipitate may have a role in correction of the coagulopathy associated with liver disease where concerns about pulmonary oedema exist.

Adult↗

Effect of ventilation equipment on imposed work of breathing.

OBJECTIVE: To determine the imposed work of different ventilation systems at 3 levels of pressure support. DESIGN: Laboratory study. SETTING: Teaching hospital respiratory laboratory. PARTICIPANTS: Healthy, human volunteers. INTERVENTIONS: Measurement of imposed work of breathing (WOB(i)) in six ventilators with alteration of ventilatory settings, humidification device, and triggering mechanisms. RESULTS: At 0 cmH2O CPAP and 0 cmH2O PSV, clinically significant (> 0.1 joules per litre or J/L) WOB(i )occurred in all systems. At 5 cmH2O pressure support ventilation (PSV) median WOB(i) ranged from 0.01 to 0.11 J/L. Removal of the pleated membrane heat and moisture exchanger (HME) significantly reduced WOB(i) (0.38 vs. 0.11 J/L, p < 0. 0001). Drawover humidification marginally increased WOB(i) (0.16 vs. 0.11 J/L, p = 0. 0001). Flow triggering reduced WOB(i) with the Servo (p < 0.0001) and Bennett ventilators (p = 0.001) but not with the Bear 1000 ventilator. CONCLUSIONS: Up to 7 cmH2O of PSV may be required to reduce WOB(i) related to the ventilator, circuit and humdification devices. This pressure support does not address the additional resistive effect of the endotracheal or tracheotomy tube. Higher levels of PSV may therefore be required to offset WOB(i).

Journal Article↗

Work of breathing measurement in the critically ill patient.

Weaning patients from mechanical ventilation in the intensive care unit can be difficult. In patients requiring prolonged ventilatory support it has been demonstrated that conventional weaning criteria are frequently incorrect. In this group measurement of respiratory work may be of benefit. Until recently, estimation of the work of breathing in patients receiving mechanical ventilation was logistically difficult. The availability of a computerized bedside monitoring device potentially allows easier estimation of the work of breathing at the bedside. The results of preliminary studies utilizing such monitoring are provocative: they highlight the phenomenon of nosocomial respiratory failure and challenge our clinical ability to determine patient workloads and timing of extubation. The potential benefits of work of breathing measurement, in particular the avoidance of respiratory muscle fatigue, earlier extubation, reduced duration of mechanical ventilation, reduction in ICU and hospital length of stay, and most importantly, a reduction in patient morbidity are yet to be demonstrated and concerns still exist about the monitor's accuracy.

Critical Illness↗

Metabolic organization of liver during spawning migration of sockeye salmon.

Although earlier studies have established broad outlines of biochemical changes during salmon spawning migration, the metabolic organization of specific organs has hitherto remained unknown. In this study, we assessed the performance of isolated liver cells from anorexic female sockeye salmon (Oncorhynchus nerka) at four sampling sites along their 1,150-km spawning migration. Isolated hepatocytes maintain high rates of gluconeogenesis and CO2 release from amino acids and lactate throughout the migration. Alanine, derived from proteolysis of white muscle, constitutes the single most important source for de novo synthesis of glucose. Just before spawning, when glycogen reserves reach a maximum, gluconeogenesis from alanine is specifically inhibited, whereas its conversion to CO2 and the utilization of other substrates are relatively unchanged. Spawning, apparently supported by carbohydrate catabolism, is accompanied by depletion of glycogen reserves from muscle as well as liver and a stimulation of gluconeogenesis from amino acids. At the onset of migration, palmitate oxidation accounts for about half the CO2 released by liver cells; its contribution decreases during the migration and is negligible after spawning.

Amino Acids↗

Amino acid utilisation in isolated hepatocytes from rainbow trout.

The utilisation (conversion to CO2 and/or glucose) of a series of amino acids by isolated trout hepatocytes was investigated and compared to the utilisation of lactate and palmitate. In fed fish, several amino acids (alanine, serine, asparagine and glycine) and lactate produced CO2 at considerably higher rates than palmitate. During starvation plus exercise, the rate of CO2 production from palmitate increased while that from lactate and most of the amino acids decreased. Gluconeogenesis from amino acids in fed fish was lower than from lactate. Serine and asparagine were the most effective substrates; alanine gave lower rates of incorporation. During prolonged starvation plus exercise, the rates of gluconeogenesis from amino acids increased twofold and, simultaneously, there was a corresponding increase in phosphoenolpyruvate carboxykinase activity in liver. It is concluded that several amino acids (dietary or released from muscle protein) are potentially major oxidative substrates in trout. In addition, amino acids appear to have the capability to maintain supplies of glucose during a period of prolonged starvation and exercise. No evidence could be found to support the contention that alanine is the most important glucogenic amino acid.

Amino Acids↗

Hydrogen shuttles in air versus water breathing fishes.

1. The malate-aspartate cycle was demonstrable in subcellular preparations of hearts from Arapaima, Lepidosiren, and Synbranchus (obligate air breathers), Hoplerythriunus (facultative air breather), and Osteoglossum and Hoplias (obligate water breathers). 2. Although no respiratory evidence for significant alpha-glycerophosphate cycle participation could be shown in the air breathers, this cycle was demonstrable in hearts of water breathers. 3. In agreement with the O2 uptake studies, it was possible to reconstruct the malate-aspartate, but not the alpha-glycerophosphate cycle, in isolated mitochondria from air breathers, while both shuttles could be reconstructed with heart mitochondria in the case of water breathing fishes.

Air↗

Pressure effects on water-swollen elastin. A model for hydrophobic interactions in proteins.

The effect of pressure on the swelling of elastin in pure water was investigated. Because elastin is a very non-polar protein, and because the swelling of elastin can be directly related to changes in the strength of hydrophobic interactions, we have used elastin as a model to study the effect of pressure on hydrophobic interactions in proteins. The elastin swelling model is particularly useful because it is based on a macromolecular system very similar to a globular protein and not on dilute aqueous solutions of small non-polar compounds. Increased pressure causes elastin to increase its swollen volume, and the observed swelling changes were analyzed in terms of the Flory-Rehner theory (Flory, P.J. and Rehner, Jr., J (1943) J. Chem. Phys. 11, 521--526) for the swelling of kinetically free, random polymer networks. Our calculations provide a measure of the volume change for the process of transferring 1 mol of an average non-polar amino acid side chain from a region where the side chains are surrounded by other non-polar groups and have no contact with water (i.e. a hydrophobic region) into contact with water. The results indicate that there is a small, negative volume change associated with this process, and quantitative estimates indicate that the volume change is of the order of --6 ml/mol side chain. The results support the hypothesis that the free energy required to transfer a non-polar side chain from a hydrophobic region into water becomes less positive (i.e. the hydrophobic interaction becomes weaker) as hydrostatic pressure is increased.

Elastin↗