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Biomedical subjects

W Zingg

Publications and source records attributed to W Zingg.

At least 19 recordsLinked to original sources

Detection and quantification of cell-free Epstein-Barr virus by polymerase chain reaction and subsequent DNA enzyme immunoassay.

Amplification by polymerase chain reaction and subsequent DNA enzyme immunoassay (DEIA) were employed to determine the number of genome equivalents of cell-free Epstein Barr virus (EBV) DNA in peripheral blood. The assay detected cell-free EBV DNA in the serum of 14 out of 18 patients with primary, productive EBV infection (sensitivity 77.7%) but not in healthy EBV carriers with latent infection (specificity 100%). Our assay has the potential for a clinical diagnostic tool to monitor patients at risk for EBV reactivation and productive infection with subsequent EBV-induced lymphoproliferative diseases.

Base Sequence

Goal-directed research.

The current model of scientific research (basic research leading to applied research, followed by technological or clinical application) has served society and the scientific community well for over fifty years. Current societal changes suggest the need for a review and the addition of a new model: support for science and technology led by social and clinical needs.

Humans

Health care technology: how can we tell if we can afford it? A Canadian viewpoint.

Major changes are reshaping the economic, political, and social climate in which Canada's health care systems operate. Cost containment has become an essential element of that climate. The perception is that health care technology is a major contributor to health care costs, and this has served as the impetus for a call for assessment and evaluation of all health care technology. While the need for health technology assessment is valid, such assessments must be much broader than simple economic assessments. A complete cost-benefit analysis of the clinical use of a given technology, including consideration of possible alternatives and the implications of rejection of that technology in certain circumstances, is complex. If we are to utilize the results of these analyses to effect important changes in health care delivery, studies must include the science behind the technology, the technology itself, the devices resulting from the technology, the medical outcome, and the societal impact in addition to pure cost considerations. Only then will we be able to properly assess the effectiveness and efficiency of health care technology in society and decide whether we can afford it.

Canada

Effect of heparin-PVA hydrogel on platelets in a chronic canine arterio-venous shunt.

Polyvinyl alcohol (PVA) hydrogel, with or without heparin, was reactive towards canine platelets in a chronic arteriovenous shunt as demonstrated by an increase in platelet regeneration time, a systemic decrease in platelet count and transient decrease in platelet serotonin content. Immobilized heparin (heparin-PVA) had no effect whereas unmodified polyethylene was found to be unreactive despite similar levels of platelet deposition as measured by SEM and a higher in vitro reactivity (J. Biomed. Mater. Res., this issue). Twenty-centimeter lengths of hydrogel coated polyethylene tubing were inserted between the arterial and venous portions of the shunt and left in place for 4-6 days, without the complicating artifacts of anticoagulation, anesthesia, or surgical intervention. Regeneration time was measured as the return to normal platelet cyclooxygenase (co) activity after a single 240-mg dose of aspirin, with co activity measured in vitro as malondialdehyde production. Although measuring new platelet production, regeneration time is an indirect measure of platelet consumption, so that the reduced regeneration time seen here was presumed to reflect enhanced material associated consumption and thromboembolism. Like other hydrogels, PVA does not appear to be "thromboadherent" but it does appear thrombogenic. Immobilized heparin had no additional effect, presumably because the platelet response was dominated by the reactivity of the underlying substrate.

Animals

Human erythrocyte adhesion and spreading on protein-coated polymer surfaces.

Protein adsorption is the first event which occurs when polymer surfaces are exposed to blood. The adsorption of proteins modifies the surface properties of the substrates and therefore influences subsequent cell-surface interactions. In an attempt to elucidate the fundamental mechanisms governing cell-proteinated-surface interactions, the extent of fresh human erythrocyte adhesion and spreading on protein-coated surfaces was examined. Five human serum proteins (albumin, fibrinogen, immunoglobulin G, fibronectin, and transferrin) were used at bulk concentrations ranging from 0.01 mg/mL to 50 mg/mL. Polymer substrates covering a wide range of wettability were employed. Protein adsorption significantly reduces erythrocyte adhesion and spreading on all test surfaces with minimum adhesion observed on fibrinogen: IgG greater than albumin greater than fibronectin greater than transferrin greater than fibrinogen. The extent of these effects is dependent on the nature of the adsorbed protein, the protein bulk concentration, and the surface properties of the underlying polymer substrates.

Biopolymers

Effect of diabetes on the healing process of synthetic grafts implanted in dogs: a preliminary study.

The deleterious effects of diabetes in peripheral vascular surgery and blood access are generally considered to be associated with the greater failure rate of vascular prostheses. To understand better these phenomena, we investigated the healing characteristics of an ePTFE graft in dogs. The animals were made diabetic after total pancreatectomy and the grafts implanted for scheduled periods of 24 h, 48 h, 1 wk and 1 month, either as thoracic (series I) or abdominal (series II) aortic substitutes. The same implantations were performed in non-diabetic dogs used as controls. The luminal surfaces of grafts implanted in diabetic dogs, either as thoracic or abdominal bypasses, proved to be more invaded by platelets as a result of the blood's increased platelet aggregation properties. The presence of endothelial-like cells spreading over the pannus after 1 month implantation was strikingly different in diabetic versus non-diabetic dogs. In the first group, the cells were fragile and less abundant, whereas in the second they were more adhesive, elongated and orientated in the direction of the blood flow.

Animals

Physical and hydrodynamic factors affecting erythrocyte adhesion to polymer surfaces.

Using a flow cell design which ensures fully developed laminar flow, the influence of various hydrodynamic and physical factors in determining the extent of erythrocyte adhesion to various polymer surfaces has been examined. Specifically we have investigated the effect of exposure time, flow rate, erythrocyte concentration, and substrate surface tension on the extent of erythrocyte adhesion. The results indicate: (1) the extent of erythrocyte adhesion is most extensive on the more hydrophobic surfaces; (2) the rate of adhesion is higher on the more hydrophobic surfaces; (3) saturation coverage occurs after 7-10 min of exposure to the erythrocyte suspension for all substrates examined. No "lag-time" in the onset of adhesion was observed; (4) The level of saturation depends on the bulk erythrocyte concentration, increasing with increasing cell concentration; (5) the extent of adhesion decreases with an increase in flow rate; and (6) substrate surface defects such as roughness have a major effect on the pattern of erythrocyte adhesion.

Biocompatible Materials

Kinetics of cell adhesion to polymer surfaces.

Results of the kinetics of adhesion of granulocytes as well as fresh and glutaraldehyde-fixed erythrocytes, suspended in Hanks Balanced Salt Solution (HBSS; pH 7.2, ionic strength of 0.15) to various polymeric substrates are presented. Cell adhesion increases rapidly initially and reaches a plateau value after approximately 30 minutes. There is no evidence for a lag-time in the onset of cell adhesion, suggesting that electrostatic double-layer forces are negligible under these experimental conditions. For the experiments in which the cells are suspended in HBSS, which has a surface tension larger than that of the cells, the level of cell adhesion increases with decreasing surface tension of the polymeric substrates. An additional experiment with fresh human granulocytes suspended in HBSS containing 10% dimethyl sulfoxide was also performed. The surface tension of the resulting liquid medium is below that of the cells and the pattern of adhesion is reversed, in agreement with the predictions of a thermodynamic model for cell adhesion. The slightly different behavior of siliconized glass as a substrate is discussed in terms of "screening."

Biocompatible Materials

Protein adsorption to polymer particles: role of surface properties.

Adsorption isotherms of four plasma proteins (fibrinogen, IgG, human serum albumin, and bovine serum albumin) using four different types of small particles as substrates (siliconized glass, Teflon, polyvinylchloride, and Nylon-6,6) are reported. The suspending liquid medium was phosphate-buffered saline, with a surface tension higher than that of any of the proteins. In keeping with the thermodynamic expectations for these systems, protein adsorption decreases for all solids in sequence from fibrinogen (the most hydrophobic) to IgG, human serum albumin, and bovine serum albumin (the most hydrophilic). Furthermore, the extent of protein adsorption also decreases from the low surface tension (hydrophobic) to the higher surface tension solids, again as expected on thermodynamic grounds. There is one minor yet interesting exception to the thermodynamic pattern: In spite of the slightly lower surface tension of siliconized glass, the extent of protein adsorption is slightly higher to Teflon than to siliconized glass. This result is attributed to the theoretically well known phenomenon of "screening."

Adsorption

Transhepatic absorption and biliary excretion of insulin.

The application of insulin to the liver in rats is followed by an increase of the insulin concentration in the bile. The pathway of insulin from the liver surface to the bile may include a secretory process by the hepatic cells, or it may bypass the hepatic cells, using direct anatomical pathways from blood and lymph to bile. The concentration of insulin in arterial and venous blood, in lymph, and in bile was measured following application of insulin to the liver surface and following peritoneal or intravenous administration. The results confirm that insulin is absorbed from the surface of the liver, but the glucose modulating effect was less effective than after intravenous administration. The insulin concentration in bile was increased after insulin administration by all routes, with the highest and most prolonged increases found after intraperitoneal administration. The results suggest that following transhepatic and intravenous administration, insulin reaches the bile without passing through the liver cells.

Absorption

Studies on transhepatic insulin absorption.

The intraperitoneal administration of insulin has been recommended because it was found to effectively control the plasma glucose level. Several authors have suggested that intraperitoneal insulin administration may be more "physiological" and therefore preferable because the insulin is absorbed into the portal venous system without, however, identifying the exact pathways. The possibility that insulin is absorbed through the surface of the liver was investigated in rats. The results show that insulin is absorbed rapidly by this route, but the effect on glucose modulation is similar to that of insulin given by other routes. In contrast, the effect on glucose modulation was delayed following insulin administration into the lower peritoneal cavity with exclusion of the liver.

Absorption

Parallel flow arteriovenous shunt for the ex vivo evaluation of heparinized materials.

The patency of heparin-polyvinyl alcohol (hep-PVA) coated polyethylene tubing was found to be significantly longer than control tubes coated with polyvinyl alcohol (PVA) but without heparin at low flow rates in dogs using a novel parallel flow arteriovenous shunt designed to avoid surgical artifacts. A standard Silastic chronic shunt (3.18 mm i.d.) was inserted between the iliac artery and vein of a dog. After a 2-week recovery period, a small diameter coated polyethylene tube (1.14 mm i.d.) was connected in parallel with the exteriorized portion of the chronic shunt through a pair of Silastic Y-connectors, so that less than 3% of the shunt flow was diverted into the test tube. The chronic shunt was reused many times over a greater than 6 month patency period, eliminating the need for frequent surgery and reducing interanimal variability in the results. The difference in patency between heparinized and control tubes was greater at higher mainshunt flow rates indicating the presence of a significant effect of the Y-connectors on platelet adhesion or aggregation. This effect was manifested in a time-dependent reduction in circulating platelet count. Scanning electron microscopy (SEM) examination of the midportion of the heparinized tubes after occlusion demonstrated the absence of platelet and fibrin deposits, unlike the control tubes without heparin. Although the Y-connectors played a significant role, they did not dominate the thrombotic processes occurring in this shunt and consequently the biological effectiveness of the immobilized heparin could be demonstrated.

Animals

Determination of the surface tension of various species of erythrocytes by means of the solidification front technique.

The solidification front technique is employed to determine the surface tension of fixed erythrocytes of dog, horse, human, chicken, and turkey. The results range from 65.5 erg/cm2 for dog erythrocytes to 67.6 erg/cm2 for turkey erythrocytes. A detailed error analysis shows that the differences obtained are statistically significant. Since cellular interactions are governed to a considerable extent by surface tension effects, it is concluded that caution needs to be exercised when results obtained for one species are used to predict the behavior of cells of another species.

Animals

Modification of platelet adhesion by antiplatelet drugs helps prevent cardiovascular complications of diabetes mellitus.

If it could be shown that: The abnormal platelet function in diabetes contributes to the development of cardiovascular complications of diabetes, the abnormal platelet function is a consequence of the diabetic state, the level of blood sugar control or insulin administration, antiplatelet drugs improve the abnormal platelet function independent of the diabetic state and its treatment, the altered platelet function induced by antiplatelet drugs diminishes the evolution of cardiovascular complications, the addition of antiplatelet drugs to the management of diabetes may be reasonable. Specifically designed animal experiments are necessary to provide the scientific basis for designing appropriate clinical trials.

Animals

DIAG: a computer-assisted dermatologic diagnostic system--clinical experience and insight.

Over the past few decades, the computer has been utilized in various ways to assist physicians in formulating their differential diagnoses, usually on an experimental basis. Following a review of the three major technics employed in computer-assisted diagnosis, statistical pattern classification, production rules, and cognitive models, a new system (DIAG) is described. The sole function of DIAG is to assist in the formulation of the differential diagnosis of skin diseases. At the beginning of the fourth year of development, the accuracy of the program in reaching diagnoses has been shown, on many occasions, to be comparable to its expert counterparts. However, it has been demonstrated that the system is not utilized within the dermatology clinic routinely. In response to this, aspects of DIAG have been modified in order to improve its clinical acceptability. Until this acceptance is achieved, these tools will not fulfill their potential to affect patient care.

Diagnosis, Computer-Assisted