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Biomedical subjects

S L Cooper

Publications and source records attributed to S L Cooper.

At least 91 records · Page 5Linked to original sources

Occurrence of adverse effects and high amantadine concentrations with influenza prophylaxis in the nursing home.

Amantadine, in a dose of 100 mg/day, is recommended for influenza prevention in older nursing home residents. We studied an influenza prevention protocol in a 98-bed community nursing home (96% female; mean age = 87.4 years). Fifty-five residents received amantadine when influenza A was confirmed. Although no further influenza cases were diagnosed, 22% experienced adverse events. Dose in mg/kg/day was significantly higher in the group experiencing adverse events (2.24 +/- 0.98 vs 1.76 +/- 0.35; P less than .01). Amantadine concentrations in 32 residents ranged from 128-5,810 ng/mL. Six residents had amantadine concentrations greater than 1,000 ng/mL. Seventy-eight percent would have qualified for further dose reduction on the basis of estimated creatinine clearance. The results suggest that adverse events may be an important problem with the 100 mg/day dose, and this dose may be excessive for influenza prophylaxis in many nursing home residents.

Accidental Falls↗

Platelet shape change and cytoskeletal reorganization on polyurethaneureas.

Understanding how platelet activation responses are affected by polymers having varied surface physicochemical properties can lead to improved materials for vascular applications. The in vitro responses of human platelets were studied upon adherence to four polyurethaneureas with different soft segments, as well as to Biomer, and to Formvar. Platelets were observed by video-enhanced light microscopy (VLM) as they adhered to polymer films. Platelets were subsequently prepared for high-voltage transmission electron microscopy (HVEM) to view the cytoskeleton and other ultrastructural features. Scanning electron microscopy (SEM) was then used to characterize cell surface morphology and to survey platelet populations. Shape change and cytoskeletal reorganization differed on the various surfaces. The extent of shape change and cytoskeletal reorganization was related to polyurethane surface energetic properties. While the most extensive shape change was observed on the hydrophilic and polar Formvar surface, the least shape change was observed on a polyethylene oxide soft segment polyurethane with similar surface-water energetic properties. Therefore properties other than surface-water energetics must be involved in determining platelet responses to different classes of polymers. HVEM also showed that cytoskeletal reorganization proceeded to completion only on Formvar. Polyurethane adherent platelets, although appearing fully spread by SEM or VLM, never exhibited complete cytoskeletal reorganization.

Biocompatible Materials↗

Properties and biological interactions of polyurethane anionomers: effect of sulfonate incorporation.

In order to investigate the factors affecting the interaction of polyurethanes and blood, a series of poly(tetramethylene oxide)-based polyurethane block copolymers was synthesized with systematically varying levels of ion incorporation in the hard segment block. A bimolecular nucleophilic substitution reaction was used to replace up to 20% of the urethane hydrogens with propyl sulfonate groups. Bulk and surface characterization was performed, and a canine ex vivo arteriovenous shunt was used to monitor initial platelet and fibrinogen deposition on these surfaces. The microphase separation and bulk physical properties were found to vary with ionic content. Surface analysis using both in vacuo (ESCA) and water-equilibrated (contact angle) methods indicated that these polymers, and especially the highly sulfonated materials, could rearrange to minimize their interfacial tension, depending on the contacting environment. Platelet deposition onto these materials decreased as the level of sulfonation increased, with the highly sulfonated polymer showing substantially less platelet spreading and activation than previously seen in the same experiment with other polymers.

Anions↗

Bulk, surface and blood-contacting properties of polyether polyurethanes modified with polydimethylsiloxane macroglycols.

The bulk, surface and blood-contacting properties of a series of polyether polyurethanes, modified with three different polydimethylsiloxane (PDMS) macroglycol segments, were evaluated. The PDMS oligomers were terminated with hydroxy-tipped end groups of varying polarity. The effect of substituting the polytetramethylene oxide (PTMO) soft segment of a base polyurethane with 5 and 15 wt% of these PDMS-containing polyols was investigated. The ultimate tensile strength and elongation at break appeared to be the bulk properties most significantly affected by the addition of the PDMS-containing polyols. Underwater contact angle data indicate that the block copolymer surface became more hydrophilic with increasing PDMS content. In a vacuum, as determined from the ESCA data, the relatively non-polar PDMS soft segments preferentially oriented at the surface with increasing PDMS incorporation. Despite the variation in the surface properties, the blood compatibility of these polymers was not significantly affected by the addition of the PDMS-containing polyols.

Animals↗

Acute and chronic canine ex vivo blood interactions with NHLBI-DTB primary reference materials.

Thrombus deposition was measured on NHLBI-DTB Primary Reference Material polyethylene (PRM-PE) and polydimethylsiloxane (PRM-SR) and their commercially available counterparts, surgical grade Intramedic polyethylene and Dow Corning Silastic. Canine blood-contacting experiments evaluating short-term (up to 60 min) and longer-term (up to 24 h) thrombus deposition were used to quantitate adherent platelets on the lumenal surface of test materials ex vivo. A similar pattern of thrombus deposition and detachment was observed for all materials in both acute and chronic blood contact. Although differences in the wall shear rates affected the absolute numbers of adherent platelets, the relative levels of thrombus deposition showed similarities between the two experiments, with the polyethylene materials as a group showing slightly less deposition than the silicone rubber materials. The PRM-PE showed the least thrombus deposition at extended exposure to blood. The PRM-SR showed the most thrombus deposition in the acute term. The overall similarity in blood compatibility and surface properties indicates the need for the inclusion of less thromboresistant and more polar reference materials.

Animals↗

Bulk, surface, and blood-contacting properties of polyetherurethanes modified with polyethylene oxide.

The bulk, surface, and blood-contacting properties of a series of polyether polyurethanes based on polyethylene oxide (PEO) (MW = 1450), polytetramethylene oxide (PTMO) (MW = 1000), and mixed PEO/PTMO soft segments were evaluated. The effect of varying the weight percentage of PEO, and thus the overall polarity of the mixed soft segment phase, was investigated. Two polymer blends prepared from a PTMO-based and a PEO-based polyurethane were also studied. Differential scanning calorimetry (DSC) and dynamic mechanical analysis indicated that the polyurethanes based on either the PEO or the PTMO soft segments are relatively phase mixed. The degree of phase mixing in the polymers increased with increasing weight fraction of PEO. As expected, water absorption and the hydrophilicity of the polymer increased with increasing PEO soft segment content. In vacuum, the PEO-rich polymers have a lower concentration of soft segment at the surface, possibly due to the migration of the polar PEO segments away from the polymer/vacuum interface. The blood-contacting results indicated that the higher PEO-containing polymers were more thrombogenic than the pure PTMO-based polyurethane. A threshold concentration of PEO in the polyurethane appeared to be required before the blood-contacting properties were significantly affected.

Absorption↗

Polyurethane support films: structure and cellular adhesion.

It is desirable to examine the cytobiology of cell adhesion to the same materials which are contemplated for use in biomedical and biotechnological devices. It is also of fundamental interest to examine adhesion to substrates with properties which are likely to influence adhesion in controlled ways. In many of these applications the materials of choice are polyurethane elastomers due to their physical properties and resistance to biodegradation. Polyurethanes have a two phase microstructure consisting of hydrophilic hard segments and hydrophobic soft segment domains. Variations of both the chemistry and the morphology of these microdomains may be produced. It is well understood that the hydrophilic/hydrophobic nature of surfaces affects cellular adhesion and the adsorption of extracellular proteins. Since polyurethane microdomains have dimensions in the range of 10-100 nm, hence the size of proteins and cell-surface receptors, polyurethane microdomain structure could influence order at the cell-material interface. Polyurethanes may be prepared as thin films with excellent properties for use as specimen supports in High Voltage transmission Electron Microscopy (HVEM) at 1 MeV. This permits the imaging of the cytoskeleton and other internal features of whole mounts of adherent cells, rather than tedious thin sectioning required for conventional TEM. Subsequently the surface morphology of these preparations may be imaged with high resolution SEM. Finally, the polyurethane itself may be stained and imaged by either HVEM or high resolution SEM in order to relate polyurethane micro-morphology to cellular features.

Biocompatible Materials↗

Albumin adsorption on alkyl chain derivatized polyurethanes: I. The effect of C-18 alkylation.

The initial adsorption rate of delipidized Human Serum Albumin (HSA) is increased by addition of C-18 alkyl chains to a polyurethane. The presence of alkyl chains does not appear to influence the total amount of HSA adsorbed after one hour exposure to a 5.0 mg/mL HSA solution. Neither does the desorption following one hour of adsorption appear to be influenced by the presence of alkyl chains. A study of the effects of solution concentration and temperature showed that the initial adsorption rates on both polymers are proportional to the protein concentration raised to the 0.36 power, and that alkylation of the polymer increases the activation energy of the initial adsorption rate above the 14 kJ/mol observed for the underivatized polyurethane. A new technique is presented to quantify the mass of adsorbed protein using Fourier transform infrared spectroscopy and attenuated total reflection optics. This technique uses the absorbance of bulk protein as an internal calibration reference, and appears to be as accurate and perhaps more precise than radiolabeling techniques.

Adsorption↗

Extraction of polyurethane block copolymers: effects on bulk and surface properties and biocompatibility.

In order to study changes occurring in polyurethane block copolymers upon solvent extraction, a base polymer containing approximately 50% polyurethane hard segment based on 4,4'-bis(p-phenyl isocyanate), 1,4-butanediol, and poly(tetramethylene oxide) of MW 1000 was synthesized. Portions of this polymer were extracted using methanol, toluene, and acetone. Multidetector gel permeation chromatography was used to characterize the effect of extraction on molecular weight and molecular weight distribution. Extraction also affected bulk and surface properties and the blood compatibility as assessed using a canine ex vivo blood-contacting experiment. Extracted materials possessed a higher molecular weight than the base polymer and had narrower molecular weight distributions. Acetone extraction resulted in the polymer with the highest ultimate tensile strength. Contrary to expectations, the surface properties and blood compatibility of the material studied were affected minimally by extraction.

Biocompatible Materials↗

Albumin adsorption on alkyl chain derivatized polyurethanes. II. The effect of alkyl chain length.

Linear alkyl chains containing 2, 10 and 18 carbon atoms were grafted to 10% of the urethane nitrogens in a polyether-polyurethane. The polyurethane was synthesized from methylene bis(p-phenyl isocyanate), 1,4-butanediol, and polytetramethylene oxide of 1000 molecular weight in a molar ratio of 3/2/1. Fourier transform infrared spectroscopy and attenuated total reflectance optics were used to study the adsorption of 5.0 mg/ml human serum albumin (HSA) at 37 degrees C to the derivatized and non-derivatized polymers. Both delipidized HSA and HSA containing 6.5 mol stearic acid per mol of albumin were used to study the effect of chain length upon the initial adsorption rate, the total amount adsorbed in 1 h, and the desorption rate. The initial adsorption rates revealed that non-specific adsorption was similar upon all four polymers. An increase in initial adsorption rate upon the C-18 derivatized polymer was attributed to a specific binding interaction between the HSA and the grafted alkyl chains. The conformational stability of the HSA also affected the adsorption rate. The total amount adsorbed after 1 h decreased as the alkyl chain length increased from 2 to 18 methylene groups. The desorption rate decreased in magnitude as the alkyl chain length increased from C-2 to C-18. These results support a hypothesis that alkyl chain length influences the interaction between albumin and an alkylated polymer system.

Adsorption↗

Effects of alkyl grafting on surface properties and blood compatibility of polyurethane block copolymers.

In order to probe the factors which affect the interaction between the surface of a multiphase polyurethane material and blood, a series of butanediol-chain-extended polyetherurethanes was synthesized. These polyurethanes contained different levels of phase separation, produced by systematically varying the hard segment chemical structure by grafting ethyl and octadecyl groups to the urethane nitrogen atom. Surface characterization using high vacuum, air-equilibrated, and water-equilibrated methods was performed. A canine ex vivo arteriovenous series shunt was used to monitor initial platelet and fibrinogen deposition on these polymers. The ex vivo response to these materials, along with contact angle and ESCA surface chemistry, was found to vary with the degree of alkyl derivatization. This study demonstrated that an increase in the degree of phase separation and also the incorporation of long chain (C18) alkyl groups can affect surface properties and improve the short-term blood compatibility of the underivatized polyurethane.

Animals↗

Properties of extruded poly(tetramethylene oxide)-polyurethane block copolymers for blood-contacting applications.

The bulk and surface properties and blood compatibility of a series of polyurethanes based on methylene bis(p-phenyl isocyanate), 1,4-butanediol, and poly(tetramethylene oxide) of molecular weight 1000 were studied. The hard-to-soft segment ratio of these multiphase polymers was varied, and the effect of substituting a poly(dimethylsiloxane)-containing polyol in place of 5% of the polyether soft segment was studied. Bulk properties such as tensile strength and modulus increased with hard segment content, as did surface wettability and ESCA nitrogen content. However, blood compatibility measured by a canine ex vivo blood-contacting experiment was not found to vary with hard/soft segment ratio. The addition of the silicone-containing polyol did not significantly lower the surface wettability, although ESCA-measured silicon content increased and physical properties were unfavourably affected by the incorporation of this co-soft segment. Incorporation of the siloxane-containing component resulted in increased platelet adhesion and fibrinogen deposition at most blood contact times in comparison with the other polyurethanes.

Animals↗

Ex vivo platelet deposition on fibronectin-preadsorbed surfaces.

Temporal platelet deposition profiles of canine plasma fibronectin (CPFN) adsorbed to different polymers ex vivo and the in vitro characteristics of CPFN adsorption were studied in an attempt to correlate the two. The maximum platelet deposition (gamma pltmax) obtained at a protein preadsorption time of 30 min was greater than that obtained using an adsorption time of 120 min for all surfaces studied. At 30 min of preadsorption, gamma pltmax was 520,560 and 1230 platelets/1000 micron2 on Biomer, polyethylene (PE) and oxidized PE (OXPE), respectively. In contrast, the platelet deposition at 120 min. of fibronectin preadsorption was about 60 approximately 90 platelets/1000 micron2 on all polymers studied. The surface concentrations of adsorbed CPFN measured using 125I-CPFN, were in the order PE greater than OXPE greater than Biomer. The adsorbed protein concentration increased with increasing adsorption time. The surface distribution of adsorbed CPFN was visualized with antibody-labelled colloidal gold and scanning electron microscopy. The extent of staining was lowest on PE, greater on Biomer, and highest on OXPE, roughly similar to the order of platelet deposition. Platelet deposition ex vivo appears to correlate with the immunogold-stainable-adsorbed protein rather than with the total amount of adsorbed protein.

Adsorption↗

Utilization of immunogold labeling to compare the adsorption behavior of fibrinogen, fibronectin and albumin on polymers.

Immunogold labeling followed by scanning electron microscopy (SEM) was used to examine the surface distribution of adsorbed plasma proteins. Adsorption was performed under various conditions on six different polymers; [low density polyethylene (PE), chromic acid-oxidized PE (OXPE), solution grade Biomer (SB), Teflon-(FEP), a laboratory synthesized polyurethane containing some zwitterions (ZW) and a polydimethylsiloxane based polyurethane (ZS) also containing zwitterions]. The proteins used were purified human and canine fibrinogen, fibronectin, and serum albumin. The immunogold staining technique was successful in the labeling of the adsorbed proteins. The adsorbed proteins were distributed differently on the polymers selected. Human and canine fibrinogen were found to cover all surfaces in a dense, uniform fashion. Albumin covered most surfaces in a less uniform fashion and on the zwitterionomers covered only a portion of the surface, leaving large bare patches. Fibronectin appeared to deposit unevenly, forming a network on part of the surface and uniformly coating other parts.

Adsorption↗