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Biomedical subjects

S L Cooper

Publications and source records attributed to S L Cooper.

At least 109 records · Page 6Linked to original sources

Relationship between intensity of hospital services and pharmacy workload.

The relationship between hospital census variables and pharmacy department workload was studied; intensity, which measures services provided per hospitalized patient per day, was used as the workload indicator. Quarterly data on inpatient pharmacy workload and hospital census were statistically analyzed for 1981 through 1985. Number of patient days, number of admissions, average length of stay (LOS), and pharmacy work units were examined. A work unit was one unit of inpatient pharmacy activity, such as one order for oral medication or one i.v. admixture; clinical services were excluded. Intensity was defined as the number of work units per patient day. Intensity as a function of intensive-care-unit (ICU) patient days was also analyzed. The number of pharmacy work units per quarter more than doubled from 1981 to 1985, while the number of admissions remained relatively constant. The average LOS decreased from 8.4 days in 1981 to 6.3 days in 1985, and the number of patient days decreased 27%. Quarterly workload intensity increased from 1.4 to 4.37 over the five-year period. Statistical analysis showed a strong inverse relationship between intensity and average LOS; LOS accounted for 92% of the variability in intensity. The number of ICU patient days, which increased 21%, had a significant effect on pharmacy workload; 30% of the variation in pharmacy workload was explained by ICU days. Intensity measures are useful in predicting pharmacy department workload.

Critical Care↗

The effect of fibrinogen sialic acid residues on ex vivo platelet deposition on biomaterials.

The effect of fibrinogen sialic acid residues on platelet deposition onto polymer surfaces was examined using a canine ex vivo shunt model. To test the hypothesis that desialylated fibrinogen may enhance platelet deposition when precoated on biomaterials, canine fibrinogen was desialylated and precoated on polyvinyl chloride (PVC) shunts. When protein-coated PVC shunts were exposed to flowing whole blood, both the native and the desialylated fibrinogen elicited the same profile of platelet deposition. This study indicates that platelet deposition and thrombus formation on biomaterial surfaces is not mediated by a mechanism which involves the sialic acid residues of fibrinogen.

Animals↗

The influence of preadsorbed canine von Willebrand factor, fibronectin and fibrinogen on ex vivo artificial surface-induced thrombosis.

We have examined the effects of preadsorption of several canine plasma proteins on surface-induced thrombogenesis in a canine ex vivo model. Our technique allowed determination of initial deposition and subsequent embolization of 51Cr-labeled platelets and 125I-fibrinogen onto and from polymeric arterio-venous shunts in non-anticoagulated canines. Segments of the tubing were removed at various time points between 2 and 120 minutes of blood contact for examination of the morphology of the thrombus by scanning electron microscopy. Thrombus deposition was measured on uncoated plasticized poly(vinyl chloride) (PVC) and PVC precoated with canine von Willebrand factor (vWF), fibronectin, partially purified fibrinogen (fibrinogen which contained vWF and fibronectin as impurities), or purified fibrinogen (fibrinogen which had been further purified to remove fibronectin and vWF). Preadsorption of all proteins studied enhanced the thrombogenic response relative to that of the uncoated surface. Precoating with vWF or partially purified fibrinogen resulted in the deposition of the greatest number of thrombi, and embolization was slower than on shunts precoated with canine fibronectin or purified fibrinogen. The deposition-embolization profiles for the fibronectin and purified fibrinogen-coated surfaces were similar. The amount and time sequence of initial adhesion and spreading of platelets was related to the extent and time sequence of peak thrombus formation. The partially purified fibrinogen-coated and vWF-coated surfaces had more adhered and spread platelets at the earliest time points and a greater number of larger thrombi at the peak deposition times. The slowest rate of platelet adhesion and spreading was seen on the purified fibrinogen-coated surface. White blood cells were present very early on surfaces precoated with vWF and partially purified fibrinogen, and were present prior to embolization on all surfaces. Major conclusions from this work indicate that, although fibrinogen and fibronectin promote thrombogenesis when adsorbed to a surface, vWF is even more active in promoting platelet deposition and in anchoring thrombi to the surface of biomaterials. Thus, differences in vWF adsorption to biomaterials may be a determinant of surface-induced thrombogenesis.

Adsorption↗

Ex vivo interactions and surface property relationships of polyetherurethanes.

Despite the use of polyurethanes in a number of blood-contacting applications, little is known about the contributing effects of the various polyurethane components in thrombogenesis. In order to investigate blood-polyurethane interactions, a number of different polyurethanes were examined in an acute canine ex vivo series shunt experiment. Multiprobe surface characterization techniques, including contact angle measurements, ESCA, ATR-IR, and SEM were used to obtain surface property information on the materials studied. The polyurethanes examined included several with different soft segment types, a series of materials with different hard segment diisocyanates and chain extenders, a series consisting of the same polymer cast from different solvents, a zwitterionomer, and a hard segment analog. Two commercial urethanes were also examined, and the effect of methanol extraction on these materials was studied. The blood-contact and surface characterization results indicated that both the surface concentration and type of hard segment were of importance in determining blood response. The relative concentration of hard segment on the polymer surface was found to affect the observed blood-material interaction, although the extent of this effect was found to depend on the hard and soft segment components of the copolymer system. Both the surface properties and thrombogenicity of a particular polyurethane were changed by casting from different solvents, indicating the need to optimize and control fabrication conditions. Methanol extraction was found to improve the thromboresistance of the commercial polyurethanes.

Animals↗

A model of deposition and embolization of proteins and platelets on biomaterial surfaces.

A theoretical model for the deposition and detachment of protein and platelets on biomaterial surfaces is presented here. This work is an extension of the model previously reported. Two mechanisms of protein and platelet removal are assumed: A characteristic time elapses before adsorbed protein detaches from the surface, carrying away platelets and protein which have deposited on top of it; and thrombi that attain a critical size are subject to hydrodynamic forces which embolize them from the surface. A theoretical distribution of thrombus sizes is assumed. Analysis of the effects of varying model parameters on predicted protein and platelet deposition reveals that the addition of the embolization process does not change the overall structure of the deposition profiles, but does significantly affect the finer details.

Adsorption↗

Surface properties and blood compatibility of polyurethaneureas.

A series of polyurethaneureas of varying soft segment type and hard/soft segment ratio were synthesized, and their bulk and surface properties evaluated. A canine ex vivo arteriovenous series shunt was used to monitor initial thrombus deposition. Significant levels of surface hard segment components are apparent in these materials. Polymers with poly(tetramethylene oxide) and poly(propylene oxide) soft segments showed blood compatibility variations with changes in hard/soft segment ratios: the more well-phase-separated materials showing lower platelet and fibrinogen deposition levels. Those trends apparent in polymers synthesized with poly(dimethylsiloxane) or poly(ethylene oxide) soft segments, but poly(dimethylsiloxane)-based materials showed higher levels of thrombus deposition than the poly(ethylene oxide)-based polymers.

Animals↗

FTIR-ATR studies of the effect of shear rate upon albumin adsorption onto polyurethaneurea.

The effect of wall shear rate upon albumin adsorption onto a polyurethaneurea, Biomer, was studied using FTIR-ATR spectroscopy. In these experiments, nondiffusion controlled adsorption was observed from 10 mg/ml solutions at known wall shear rates. Results show that increasing wall shear rate during adsorption does not significantly affect the adsorption kinetics, but does decrease the rate of protein desorption. These results suggest that albumin adsorbed at higher shear rates is more tightly bound to the surface. Comparison of the data to simple mathematical models suggests that more than one layer of protein adsorbs in 2 h.

Adsorption↗

Fourier transform infrared spectroscopic studies of plasma protein adsorption under well defined flow conditions.

In this study protein adsorption was monitored under well-defined and nearly uniform flow conditions at the test surface. The adsorption profiles observed demonstrated that both tightly and loosely bound proteins may be present on the surface. An understanding of these differently adsorbed species is useful since it appears that they mediate the blood response to artificial materials. The change of characteristic peak positions observed for fibrinogen on germanium and Biomer surfaces may be significant if these spectral differences can be related to changes in protein structure and the in vivo performance of different biomaterials. Finally, the ability to study competitive adsorption is important since advances in this area may eventually led to an understanding of the role adsorbed proteins play in whole blood contact with artificial surfaces.

Adsorption↗

In vitro vs. ex vivo platelet deposition on polymer surfaces.

The initial adherence and activation of platelets on a surface may be a major determinant of the thrombogenicity of that surface. The response of platelets to four polymers: polyethylene (PE), polyvinyl chloride (PVC), silicone rubber (SIL), and oxidized polyethylene (OX-PE) was studied in vitro with scanning electron microscopy. Platelets from mongrel canines and rhesus monkeys were obtained just prior to cannulation of the donor animal with an ex vivo arteriovenous series shunt evaluating the same four polymers. Thus, the in vivo response of circulating platelets could be compared to the in vitro response of purified platelets from the same animal. In the canine the in vitro response of individual platelets deposited on the four polymers studied was nearly the same as the ex vivo response although the extent of shape-change was usually somewhat greater ex vivo. Large numbers of fully spread platelets were seen on OX-PE and fewer numbers on PE both in vitro and ex vivo. Mixtures of platelets in all degrees of shape-change/activation wer characteristic on PVC, while platelets on SIL showed little shape-change over all time intervals. Rhesus platelet response was similar to the canines' except that fewer attached or shape-changed, and differences in responses to the four polymers were less pronounced. The similarity of the in vitro to the ex vivo response in each of the species suggests that this simple in vitro model can be informative in studying platelet shape-change/activation as a precursor to surface induced thrombosis with less complexity and expense than in vivo methods.

Adenosine Diphosphate↗

Physicochemical characterization and in vivo blood tolerability of cast and extruded Biomer.

Solution grade and extruded grade Biomer (SB and EB, respectively) are polyurethanes that have been suggested for use in biomedical applications. The bulk materials were examined by elemental analysis, differential scanning calorimetry, thermomechanical testing, and stress-strain testing. The extruded grade material has a lower soft segment molecular weight (650 g/mol) than the solution grade material (2000 g/mol). As a result of its higher molecular weight, the soft segment phase of SB is semicrystalline in the solid state. The hard segments of the extruded grade material are chain extended with water yielding a lower urea concentration than in the solution grade material in which the hard segments are chain extended with diamines. Chemical structures for the two materials consistent with elemental analysis, urea/urethane ratios and thermal and mechanical data, are proposed. X-ray photoelectron spectroscopy (ESCA) was used to analyze the surfaces of extruded grade Biomer, solution grade Biomer cast on the inner surface of polyethylene tubing, and extruded grade Biomer dissolved in DMA and similarly cast on polyethylene (CB). Soft segment concentrations were highest on the EB surface and lowest on the SB surface. Soft segment concentrations on the EB surface were higher than on the CB surface, indicating that the method of fabrication affected the composition of the surface layer. The three materials were tested for blood tolerance in a canine femoral arteriovenous shunt configuration. Blood compatibility was correlated with increasing concentration of polyether soft segments on the surface.

Animals↗

Morphological changes occurring during thrombogenesis and embolization on biomaterials in a canine ex-vivo series shunt.

An acute canine ex-vivo femoral A-V shunt technique was used to study thrombus formation and embolization on a number of porous and non-porous polymer surfaces over a one-hour blood contact period. The technique allows for simultaneous exposure of all the surfaces under similar physiological and hematological conditions. This makes comparisons between surfaces more reliable. SEM was used to study changes in the morphology of platelets and thrombi present on the polymer surfaces. Quantitative information was obtained using radiolabeled platelets. In general, platelet deposition, activation, and aggregation was followed by thrombus formation which peaked at about 15-30 minutes of blood contact. Thrombi were composed mainly of platelets with few leukocytes present. Embolization was observed on Silastic (SIL), polyvinylchoride (PVC), polyethylene (PE), and oxidized polyethylene (OX-PE) surfaces between 20 and 60 minutes of blood contact. The mechanism for embolization involved clot retraction under the influence of a shear field. Leukocytes did not appear to be necessary for the initiation of embolization but were present during the embolization phase on OX-PE, possibly due to chemotactic factors. Although extensive thrombus formation was observed on the porous PTFE materials (GORE-TEX and IMPRA), the thrombi formed were flat and did not significantly block the lumen. By 60 minutes of blood contact, only minimal embolization had occurred on the PTFE surfaces. SEM examination of the sequence of thrombus formation and embolization was found to correlate well with trends in platelet deposition measured using radiolabeling techniques.

Animals↗

Binding of plasma fibronectin to monolayer human endothelium.

Interaction of exogenous plasma fibronectin with endothelium was examined using monolayer cultures of human umbilical vein endothelial cells. Plasma fibronectin was purified on gelatin-sepharose with 1 M arginine elution and iodinated with 125I by the solid phase glycoluril method. Endothelial monolayers were incubated with 0.5 to 15.0 mg/l (125I)fibronectin. Specificity of binding was 50 to 60% as determined by competition with 50-fold excess nonlabeled fibronectin. Binding reached maximal levels within 1 hour and without saturation over the concentration range. The bound glycoprotein showed minimal dissociation during subsequent incubation in media free of fibronectin.

Cells, Cultured↗