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Biomedical subjects

R D Hughes

Publications and source records attributed to R D Hughes.

At least 19 recordsLinked to original sources
PubMed1992

In vitro plasma perfusion through adsorbents and plasma ultrafiltration to remove endotoxin and cytokines.

In vitro plasma perfusion experiments were performed using small columns containing either resin or charcoal adsorbents to assess the removal of cytokines and endotoxin. 125I-labelled tumor necrosis factor-alpha (TNF-alpha; 500 pg/ml) and interleukin-6 (IL-6; 10 ng/ml) were added individually to human plasma. Over 4 hr of perfusion, Amberlite XAD-7 resin removed 32.5% +/- 3.3% (n = 5) of the initial amount of TNF-alpha and 71.4% +/- 3.8% (n = 5) of the initial amount of IL-6. DHP-1 polyhema-coated activated charcoal removed 17.2% +/- 6.2% (n = 5) of TNF-alpha and 48.5% +/- 7.4% (n = 5) of IL-6. Preliminary experiments were performed with lipopolysaccharide (LPS; 100 ng/ml) and interleukin-1 alpha (IL-1 alpha; 500 pg/ml), which showed that, over 4 hr, Amberlite XAD-7 removed 10.3% of the initial LPS and 29.1% of IL-1 alpha, whereas DHP-1 charcoal removed 23.2% of the initial LPS and 65.3% of IL-1 alpha. In vitro plasma ultrafiltration with either polysulfone or polyacrylonitrile membranes, as used clinically in haemodialysis, was performed with recirculation of plasma containing LPS or TNF-alpha. Neither of the substances was filtered to a significant degree. In conclusion, direct removal of these inflammatory mediators from the circulation of patients with multiorgan failure due to fulminant hepatic failure or sepsis would be possible by perfusion of plasma through adsorbents but not by haemodialysis.

Adsorption↗
PubMed1979

Adsorption of human serum albumin to Amberlite XAD-7 resin.

In the present study the conditions leading to tight binding of human serum albumin to the Amberlite XAD-7 resin without the use of chemical coupling agents have been defined. Optimal binding (10.97 mm/kg dry XAD-7) was achieved at pH 5.0 and adsorption conformed to a Langmuir isotherm. Theoretical analysis of the data suggest adsorption of a monolayer of albumin which is supported by the absence of visual surface coating on scanning electron micrographs. Binding of human serum albumin was reduced when two chemical coupling agents, glutaraldehyde and carbodiimide were included in the human serum albumin solution, the elution of adsorbed HSA from the resins under severe flow conditions was reduced, and the amount eluted was minimal in all instances.

Acrylic Resins↗
PubMed1979

Albumin-coated Amberlite XAD-7 resin for hemoperfusion in acute liver failure. Part I: adsorption studies.

Platelets adhere to most foreign surfaces. As a result, polymers and albumin have been suggested as possible coatings to improve the blood compatibility of such surfaces. Amberlite XAD-7 has a high affinity for human serum albumin (HSA) and several protein-bound toxic metabolites. In the present study it is shown that HSA can be tightly bound to Amberlite XAD-7 without the use of chemical coupling agents. Optimal binding was achieved at pH 5.0 and the adsorption conforms to Langmuir's isotherm. Theoretical analysis of data and absence of a residual surface coating visible with scanning electron microscopy suggest a monolayer of albumin. The amount of HSA eluted from the resin under severe flow conditions was negligible (approximately 1%). Furthermore, in stirred batch studies with human plasma, the HSA coating did not decrease the adsorptive capacity of XAD-7 for bile acids and bilirubin.

Acrylic Resins↗
PubMed1979

The use of prostacyclin, PGI2, in the prevention of platelet aggregation during charcoal haemoperfusion.

In previous studies severe side effects, including irreversible hypotension, platelet losses and rises in Swank screen filtration pressure, have been recorded during the treatment by charcoal haemoperfusion of patients with fulminant hepatic failure. It has also been demonstrated that rises in Swank screen filtration pressure in an in vitro test circuit are due to the presence of platelet aggregates. In this study Prostacyclin was infused at a constant rate, to give a blood concentration of 5 ng/ml, into the in vitro circuit just prior to the charcoal column. Rises in Swank screen filtration pressure were prevented, and it was also shown that the giving of a bolus dose of Prostacyclin (400 ng/ml blood concentration) reversed rises in Swank screen filtration pressure that have already occurred. On the basis of these findings, Prostacyclin would be expected to be of considerable clinical value in the prevention of adverse platelet reactions to charcoal haemoperfusion when carried out in patients with fulminant hepatic failure.

Adenosine Diphosphate↗
PubMed1978

The use of an in vitro haemoperfusion circuit to evaluate the blood compatibility of albumin-coated Amberlite XAD-7 resin.

We have developed an in vitro haemoperfusion circuit, which closely simulates the conditions encountered in a clinical haemoperfusion, for testing the blood compatibility of new adsorbent materials. Fresh heparinised human blood is perfused for 2 hours over two model columns arranged in parallel closed circuits. The present study was performed to investigate the blood compatibility of human serum albumin-coated Amberlite XAD-7 resin. Mean platelet losses over 2 hours were greater following perfusion of the uncoated resin (44 +/- SE 5.6%) than the albumin-coated resin (17 +/- SE 2.2%) (p less than 0.01). Mean white cell losses were similar (55%) for both resins. No rises in Swank screen filtration pressure, which detects the presence of cellular aggregates in blood, were observed. Coating of XAD-7 resin with HSA therefore improves its blood compatibility with respect to platelet losses and we thus intend to use this preparation in a clinical trial of resin haemoperfusion in fulminant hepatic failure.

Acrylic Resins↗
PubMed1978

Effects of arm training on retention of training effects derived from leg training.

This study examined the effects of arm training on retention of training effects produced by leg training. Thirteen adult male subjects leg trained on bicycle ergometers for 8 weeks. During the subsequent 4 week control period group AT (N = 4) arm trained by cranking an ergometer, group DT (N = 4) discontinued training and group LT (N = 5) continued leg training. Metabolic response to maximal and submaximal (80% initial Vo2max) leg work was observed before (Test I) and after (Test II) the 8 week leg training program and at the conclusion of the control period (Test III). With the initial 8 weeks of leg training Vo2max and maximal Ve increased while Vo2, HR, Ve and blood lactate decreased during submaximal work (p less than .05). R was decreased during both maximal and submaximal work (p less than .05). Analysis of covariance of the Test III means (Test II as covariate) yielded significant (p less than .05)F-ratios for Vo2max and R at Vo2max. Post hoc testing indicated that Vo2max was greater in LT than in AT or DT but that there was no difference between AT and DT. R at Vo2max was greater in DT than in LT or AT. These data suggest that arm training does not significantly affect the deterioration in metabolic response to leg work which occurs with cessation of leg training.

Adolescent↗
PubMed1977

Studies on plasma cytotoxicity and liver regeneration in fulminant hepatic failure.

The possibility that the blood of patients with fulminant hepatic failure might contain substances which prevent or delay liver regeneration was investigated using a microcytotoxicity assay system based on the culture of isolated rabbit hepatocytes in vitro. Results showed significant cytotoxicity of the plasma as compared to controls, an effect which was reduced by charcoal haemoperfusion. The effect was also reduced in vitro by heating and dialysis. The bile acids chenodeoxycholic and lithocholic acid were cytotoxic when added to control human plasma. Evidence was also obtained from a completely different in vivo assay system that high blood levels of ammonia may inhibit hepatic regeneration.

Ammonia↗
PubMed1977

Early prediction of the outcome of a paracetamol overdose based on an analysis of 163 patients.

Clinical and biochemical data obtained from 163 patients who had taken an overdose of paracetamol were examined to determine which factors or measurements were of value in predicting the severity of ensuing liver damage early after ingestion of tablets. Although the overall severity of hepatic necrosis was found to increase with the dose of paracetamol ingested, correlation was not sufficiently close to provide an accurate prognostic index in individuals. Severe hepatic damage was less likely if the patient had vomited or had a stomach wash-out within 6 hr of overdose. The plasma concentrations of paracetamol, measured at known times after overdose, distinguished those who developed hepatic dysfunction from those who did not, but there was a poor correlation, particularly in the first 6 hr after ingestion of tablets, between these values and the severity of ensuing liver damage. Estimates of early plasma paracetamol half-lives from three or more samples taken within 4 hr of admission showed that all patients developing moderate or severe liver damage had half-lives greater than 4 hr, but this was also the case in nearly one-third of those with minimal liver lesions only. It is concluded that there is no completely reliable early prognostic test for individual patients with paracetamol overdose. If each patient is selected for treatment with cysteamine (mercaptamine) or other agents on the basis of plasma paracetamol levels, up to 30% may receive this agent who are at risk from trivial hepatic damage only.

Acetaminophen↗
PubMed1977

Affinity chromatography systems for artificial liver support.

The physical, adsorptive, and flow properties of two albumin conjugated agarose materials have been investigated in vitro to determine whether they could be used in artificial liver support systems to enhance the removal of toxic protein-bound substances. The results of binding of chenodeoxycholic acid and unconjugated bilirubin and flow experiments with blood and saline suggested that there could be advantages in using the SepharoseR rather than Bio--GelR albumin agarose in future haemoperfusion systems. However, further modifications are needed before the former can be successfully scaled up for human use.

Chromatography, Affinity↗
PubMed1976

The cytotoxicity of plasma from patients with acute hepatic failure to isolated rabbit hepatocytes.

The cytotoxicity of plasma from patients with various types of liver disease to rabbit hepatocytes maintained in vitro has been investigated using a microcytotoxicity assay system. Plasma from patients with fulminant hepatic failure and uncomplicated viral hepatitis showed significant cytotoxicity compared to controls. The cytotoxic effect of plasma from patients with fulminant hepatic failure was reduced by charcoal haemoperfusion, or heating and dialysis. The bile acids chenodeoxycholic acid and lithocholic acid were cytotoxic when added to control human plasma. Such toxic factors may be responsible for the delay in liver regeneration often seen in patients with fulminant hepatic failure.

Animals↗
PubMed1975

Resin column perfusion with whole blood or plasma separated by the continuous flow celltrifuge.

1. The aim of this study was to define the factors influencing plasma separation from the continuous flow celltrifuge and to evaluate plasma as an alternative to whole blood for perfusion of exchange resins as part of a system of artificial liver support. 2. Studies in vitro showed the importance of packed cell volume, centrifugal force and duration of centrifugation on the degree of plasma separation. From these data it was possible to calculate plasma flow rates likely to be obtained from the celltrifuge when used in vivo. These predicted values correlated closely with plasma flow rate obtained in twenty-six studies in dogs. 3. Comparison of whole blood perfusion with plasma perfusion of exchange resins in another series of dog experiments showed that with whole blood perfusion there was often a considerable rise in pressure across the resin column but that this did not occur with plasma perfusion. 4. Measurements of platelet losses in the same series of experiments showed a 50% reduction of arterial platelet counts over a 31/2 h period of perfusion when whole blood was perfused. Although the fall was lower with plasma perfusion, the difference was not statistically significant. 5. Use of the celltrifuge provides a means of resin perfusion free of the mechanical difficulties of whole blood perfusion, but platelet losses still remain a problem.

Animals↗