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Biomedical subjects

C A Ward

Publications and source records attributed to C A Ward.

At least 55 records · Page 3Linked to original sources

Activation of complement at plasma-air or serum-air interface of rabbits.

The possibility of the air-plasma interface giving rise to complement activation is investigated. After incubation of the plasma of a group of rabbits with zymosan and measurement of the degree of autologous polymorphonuclear leukocyte aggregation that follows the injection of a sample of the incubated plasma into a leukocyte suspension, it is found that the rabbits can be divided into two groups, sensitive and insensitive, depending on the degree of leukocytes aggregation. For the sensitive group it is found that both the plasma-air interface and the serum-air interface give rise to significant leukocyte aggregation. If the animal is decomplemented before the plasma is incubated in the presence of the air interface, there is no longer any significant leukocyte aggregation. It would appear that the complement system is activated by the presence of the air interface in plasma, but that fibrinogen does not play a pivotal role in the process.

Air↗

DNA methylation: sequences flanking C-G pairs modulate the specificity of the human DNA methylase.

Synthetic single-stranded oligodeoxynucleotides of known sequence have been used as in vitro substrates for a partially purified HeLa cell DNA methylase. Although most oligonucleotides tested cannot be used by the HeLa DNA methylase in vitro, we have found a unique 27mer, containing 2 C-G pairs, that is an excellent substrate for the enzyme. Analysis of the methylation of the 27mer, its derivatives and other oligomer substrates reveal that the HeLa DNA methylase does not significantly methylate an oligomer which contains just one C-G pair. In addition, only one of the two C-G pairs in the 27mer is methylated and this methylation is abolished if the other C-G pair is converted to a C-A pair. Furthermore, the HeLa enzyme apparently cannot methylate C-G pairs located in compounds containing a high A + T content. The most efficient methylation occurs with multiple separated C-G pairs in a compound with a high G + C content (greater than 65%). The results suggest that clustering of C-G pairs in regions of the DNA high in G + C content may be the preferred site for DNA methylation in vivo.

Base Composition↗

The effect of flanking sequences on the de novo methylation of C-G pairs by the human DNA methylase.

The HeLa DNA methylase can methylate selected cytosine residues in oligodeoxynucleotides as small as 12-16 nucleotides in length in vitro. The maximum methylation rate seems to require oligomers having more than one C-G in the molecule even when only one of the C-G pairs is methylated. Compounds which contain a high G+C content also seem to be favored substrates. The use of defined synthetic oligodeoxynucleotides permits one to demonstrate that flanking DNA sequences can be critical in determining whether a C-G site can be methylated.

Base Composition↗

Reduction in complement activation from biomaterials by removal of air nuclei from the surface roughness.

The activation of the rabbit complement system by each of three different synthetic materials is reported. Samples of each type of material were subjected to one of two different priming procedures. One priming procedure was intended to remove the air nuclei from the surface roughness of the materials; the other procedure was just the normal one. It was found that the removal of the air nuclei during priming reduced the complement activation by each of the two materials of lower surface tension, but not by a statistically significant amount for the material of highest surface tension, cellophane. For the denucleated samples of the three materials, the amount of complement activation was found to correlate with the critical surface tension of the materials; if the samples of the materials were normally primed, there was no correlation of the amount of complement activation with the critical surface tension of the material.

Air↗

Fracture studies on a mammalian semicircular canal.

In the present work the pressures necessary to fracture the semicircular canal of the mammalian inner ear, specifically the squirrel monkey, have been investigated experimentally. The results indicate that individual canals can fracture when subjected to internal pressures of approximately 1.6 +/- 0.4 MPa. Simulation testing using Plexiglas and polycarbonate specimens, to represent the location of a possible osteoclast site within the bone forming a semicircular canal, demonstrates further that fracture of the canal can be initiated at this or even lower pressures when the pressure is generated within a simulated osteoclast site. These results provide useful information for a better understanding of the mechanisms by which bubble nucleation and growth could cause pressures of this magnitude within an osteoclast cavity during the decompression phase of a diving schedule.

Animals↗

Failure of delayed hypersensitivity skin testing to predict postoperative sepsis and mortality.

Delayed hypersensitivity skin reactions to a battery of recall antigens, haemoglobin and albumin concentrations, arm-muscle circumference, and percentage of ideal weight were determined before operation in 244 patients undergoing elective major surgery. Depressed skin reactions were found in 70 patients (28%), but this group did not have significantly higher sepsis or mortality rates when compared with patients with normal reactions. Significant associations were found between depressed skin reactions and increasing age, anaemia, hypoalbuminaemia, low arm-muscle circumference, and low weight. Patients with benign and malignant disease had similar distributions of skin reactions. Hypoalbuminaemia was associated with a higher rate of serious postoperative sepsis, and hypoalbuminaemia, low arm-muscle circumference, and low weight were all associated with a higher mortality. These results suggest that the routine use of delayed hypersensitivity skin testing in the preoperative assessment of surgical patients is not justified.

Abdomen↗

Enhancement of thrombus formation by vascular prostheses.

The stagnation point flow experiment has been used to identify the microscopic events that occur in thrombus formation on foreign surfaces. In this investigation it was used to study the role of vascular grafts in preactivating blood, as well as the role of pretreatment of these grafts to remove the gas nuclei. The experiment was carried out under two conditions: (a) in which whole blood was led from the carotid artery of a dog to the undersurface of a microscope coverslip (control experiment) and (b) in which blood flowed from the left carotid artery of the dog through a 10-cm vascular graft to the right carotid artery and finally to the flow chamber for visualization. The thrombus morphology, time to thrombus formation and thrombus adhesiveness to the foreign surfaces were compared using knitted Dacron, woven Dacron, expanded polytetrafluoroethylene (PTFE) and saphenous vein grafts. Blood led through the vascular grafts showed a marked predisposition to thrombus formation, with no change in clotting times. Knitted Dacron most highly preactivated the blood, while PTFE showed a lesser degree of preactivation. Treating expanded PTFE so that it may be completely wetted eliminated any activation of blood and caused blood to behave as if it had not contacted a foreign surface. It was the only graft material, including autogenous vein to demonstrate this property. Therefore, of the materials tested, hydrophobic Teflon with no entrapped gas appears blood compatible.

Animals↗

Biocompatibility of standard and silica-free silicone rubber membrane oxygenators.

Spiral coil membrane oxygenators made from either standard silicone rubber or silica-free silicone rubber were compared using three priming techniques. Standard priming, carbon dioxide priming, and denucleation priming were employed with each type of device. Four-hour venovenous membrane oxygenator perfusions were carried out on awake sheep anticoagulated with heparin. Virtually no differences were observed in any parameters measured between standard silicone rubber and filler-free silicone rubber membranes. Significantly greater platelet losses occurred during the first hour of perfusion with standard priming and with carbon dioxide priming than with denucleation priming, using either type of membrane. These experiments demonstrate that denucleation priming reduces platelet losses during extracorporeal membrane oxygenator perfusion, but that the use of filler-free silicone rubber does not improve the biocompatibility of the membrane.

Animals↗

Microbubble elimination during priming improves biocompatibility of membrane oxygenators.

We tested the hypothesis that platelet loss following blood contact with foreign materials is partly related to the presence of microbubbles of gas (gas nuclei) trapped in surface defects on the membrane material. Extracorporeal membrane oxygenator perfusions were conducted in two groups of sheep, with use of standard priming techniques for the oxygenator in one group and a new vacuum priming technique in the other group. The vacuum priming technique was developed to eliminate gas nuclei from the oxygenator surface. With denucleation priming, platelet loss during perfusion was markedly reduced, as was thrombus formation on the membrane surface. The platelet particle-size distribution curve showed a shift consistent with platelet aggregation with the standard priming technique but not with the vacuum priming technique. We conclude that the elimination of trapped gas nuclei from the membrane surface during priming reduces the initial interaction between blood elements and the foreign surface.

Animals↗

Determinants of anticoagulant control in patients receiving warfarin.

1 A hospital-based drug information system has been used to assess the time for which patients treated with warfarin were outside the range of Thrombotest values 5-10% and 5-15% and to examine possible contributory factors in situations where anticoagulation fell outside these ranges. 2 Anticoagulant control varied with the age of the patient and with concomitant drug therapy but not with patient sex or indication of anticoagulation. 3 Most patients were 'under-anticoagulated' at some stage but patients over 70 years spent significantly longer in the 5-10% range than those in the age range 30-59 years and Thrombotest values of less than 5% were found predominantly in the older group. 4 Patients given drugs known to interact with warfarin spent least time in the defined Thrombotest ranges. Those on drugs known to potentiate warfarin effect had significantly lower Thrombotest values than the other patients studied.

Adult↗

Relation of proteins, platelets, and gas nuclei in adhesion to a synthetic material.

We report the result of exposing silicone rubber to washed pig platelet suspensions that contained on average 0.018 mg of proteins/ml in solutions. This protein content is sufficiently low to reasonably neglect the protein adhesion to the material. On comparing the measured platelet adhesion from the platelet suspensions with that from blood, we find that when the gas nuclei normally present in the surface roughness of the material are removed the number of adhering platelets is the same. Thus, in the absence of the gas nuclei, the proteins in blood plasma play a negligible role in the platelet adhesion. In contrast, when both the gas nuclei and proteins are present, the maximum platelet adhesion was observed. From this and the above observation, it appears the gas nuclei affect one or more of the proteins, and this brings about an increased platelet adhesion. Finally, the platelet adhesion from the platelet suspensions was reduced after the removal of the gas nuclei. Thus the platelets themselves sense the change in the surface resulting from the removal of the gas nuclei.

Animals↗

The role of surface thermodynamics in thromboresistance of biomaterials.

A thermodynamic approach to the problem of platelet adsorption out of a suspension on to a smooth and homogeneous solid surface is developed. The interfacial tension values required may be estimated from contact angle data by means of an equation of state relation. According to the thermodynamic approach the functional dependence of platelet adsorption on surface tension of the solid differs according to whether the surface tension of the platelets is smaller or larger than the surface tension of the liquid in which they are suspended. The implications of this thermodynamic approach in situations where plasma proteins are present and the biomaterials surfaces may be heterogeneous and rough are discussed. Previous analyses using the critical surface tension of wetting and other surface-related parameters are compared with the thermodynamic analysis given here.

Biocompatible Materials↗